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Sample records for electrophysiological study biodistribution

  1. Studies on the biodistribution of dextrin nanoparticles

    International Nuclear Information System (INIS)

    Goncalves, C; Gama, F M; Ferreira, M F M; Martins, J A; Santos, A C; Prata, M I M; Geraldes, C F G C

    2010-01-01

    The characterization of biodistribution is a central requirement in the development of biomedical applications based on the use of nanoparticles, in particular for controlled drug delivery. The blood circulation time, organ biodistribution and rate of excretion must be well characterized in the process of product development. In this work, the biodistribution of recently developed self-assembled dextrin nanoparticles is addressed. Functionalization of the dextrin nanoparticles with a DOTA-monoamide-type metal chelator, via click chemistry, is described. The metal chelator functionalized nanoparticles were labelled with a γ-emitting 153 Sm 3+ radioisotope and the blood clearance rate and organ biodistribution of the nanoparticles were obtained. The effect of PEG surface coating on the blood clearance rate and organ biodistribution of the nanoparticles was also studied.

  2. Studies on the biodistribution of dextrin nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Goncalves, C; Gama, F M [IBB-Institute for Biotechnology and Bioengineering, Centre for Biological Engineering, Minho University, Campus de Gualtar, 4710-057 Braga (Portugal); Ferreira, M F M; Martins, J A [Departamento de Quimica, Universidade do Minho, Campus de Gualtar, 4710-057 Braga (Portugal); Santos, A C; Prata, M I M [IBILI, Faculty of Medicine of the University of Coimbra, Coimbra (Portugal); Geraldes, C F G C, E-mail: fmgama@deb.uminho.pt [Departamento de Ciencias da Vida, Faculdade de Ciencia e Tecnologia e Centro de Neurociencias e Biologia Celular, Universidade de Coimbra (Portugal)

    2010-07-23

    The characterization of biodistribution is a central requirement in the development of biomedical applications based on the use of nanoparticles, in particular for controlled drug delivery. The blood circulation time, organ biodistribution and rate of excretion must be well characterized in the process of product development. In this work, the biodistribution of recently developed self-assembled dextrin nanoparticles is addressed. Functionalization of the dextrin nanoparticles with a DOTA-monoamide-type metal chelator, via click chemistry, is described. The metal chelator functionalized nanoparticles were labelled with a {gamma}-emitting {sup 153}Sm{sup 3+} radioisotope and the blood clearance rate and organ biodistribution of the nanoparticles were obtained. The effect of PEG surface coating on the blood clearance rate and organ biodistribution of the nanoparticles was also studied.

  3. Toxicology and Biodistribution: The Clinical Value of Animal Biodistribution Studies

    Directory of Open Access Journals (Sweden)

    Beatriz Silva Lima

    2018-03-01

    Full Text Available Since the human genome decoding, understanding and identification of genetic disturbances behind many diseases, including cancer, are intensively increasing. Scientific and technological advances in this area trigger the search for therapeutic (curative approaches targeting the correction of gene disturbances. Gene therapy medicinal products (GTMPs emerge in this context, bringing new challenges for their characterization. Compared to small molecules, biodistribution is fundamental to identifying target organs and anticipating safety and efficacy, may be integrated into safety and pharmacology studies, and may eventually be anticipated based on specificities of vectors and constructs. This review describes and discusses the requirements for nonclinical development and evaluation of GTMPs versus conventional ones and the needs and challenges of constructing nonclinical packages that assure GTMPs’ human safety from early development, taking into consideration usefulness and/or limitations of many conventional, preclinical models. The experience gained in the European context is referenced.

  4. Dosimetry implications of BSH biodistribution study at OSU

    International Nuclear Information System (INIS)

    Gupta, N.; Albertson, B.J.; Gahbauer, R.A.; Barth, R.F.; Goodman, J.H.

    2000-01-01

    A BSH biodistribution study was performed at Ohio State University, where tumor, normal brain, and blood boron concentrations of patients undergoing tumor debulking surgery were acquired. The results of this biodistribution study are subjects of other presentations in this meeting. In this paper, we present an overview of the dosimetry implications of this biodistribution data. The analysis for this paper assumed that the tumor boron RBE was factor of two higher than the normal brain boron RBE. Our conclusions from this analysis were that with the tumor/blood ratios observed in our patients for times of up to 14 hours post commencement of boron infusion, one could not successfully treat patients with BNCT using BSH. (author)

  5. Single dose toxicity and biodistribution studies of [18F] fluorocholine

    International Nuclear Information System (INIS)

    Campos, Danielle C.; Santos, Priscilla F.; Silveira, Marina B.; Ferreira, Soraya Z.; Malamut, Carlos; Silva, Juliana B. da; Souza, Cristina M.; Campos, Liliane C.; Ferreira, Enio; Araujo, Marina R.; Cassali, Geovanni D.

    2013-01-01

    [ 18 F]Fluorocholine ( 18 FCH) is a valuable tool for non-invasive diagnosis using positron emission tomography (PET). This radiotracer has been proven to be highly effective in detecting recurrences and staging prostate cancer, diagnoses brain, breast, and esophageal tumors and also hepatocellular carcinoma. The higher uptake of fluorocholine by malignant tumors results from increased choline kinase activity due to accelerated cell multiplication and membrane formation. According to the Brazilian Health Surveillance Agency (ANVISA), radiopharmaceuticals have to be registered before commercialization. The aim of this work was to evaluate single dose toxicity and biodistribution of 18 FCH in mice, since preclinical safety studies are required for register. Experimental procedures were approved by the Ethics Committee on Animal Use (CEUA-IPEN/SP). Single dose toxicity and biodistribution studies were conducted in Swiss mice. No signs of toxicity were observed during clinical trial. No changes in the parameters which were examined, such as: body weight, food consumption, clinical pathology parameters or lesions microscopic were noted. Biodistribution results indicated high physiological tracer uptake in kidney, liver and heart 30 min after injection. Lower activities were recorded in other organs/tissues: pancreas, intestine, spleen, bone, bladder, muscle, brain and blood. Initial preclinical investigations showed no toxic effects of 18 FCH at investigated doses and a biodistribution profile very similar to other reports in literature. This information is essential to support future human trials. (author)

  6. Nanobarcoding for improved nanoparticle detection in nanomedical biodistribution studies

    Science.gov (United States)

    Eustaquio, Trisha

    Determination of the fate of nanoparticles (NPs) in a biological system, or NP biodistribution, is critical in evaluating a NP formulation for nanomedicine. Unlike small-molecule drugs, NPs impose unique challenges in the design of appropriate biodistribution studies due to their small size and subsequent detection signal. Current methods to determine NP biodistribution are greatly inadequate due to their limited detection thresholds. There is an overwhelming need for a sensitive and efficient imaging-based method that can (1) detect and measure small numbers of NPs of various types, ideally single NPs, (2) associate preferential NP uptake with histological cell type by preserving spatial information in samples, and (3) allow for relatively quick and accurate NP detection in in vitro (and possibly ex vivo) samples for comprehensive NP biodistribution studies. Herein, a novel method for improved NP detection is proposed, coined "nanobarcoding." Nanobarcoding utilizes a non-endogenous oligonucleotide, or "nanobarcode" (NB), conjugated to the NP surface to amplify the detection signal from a single NP via in situ polymerase chain reaction (ISPCR), and this signal amplification will facilitate rapid and precise detection of single NPs inside cells over large areas of sample such that more sophisticated studies can be performed on the NP-positive subpopulation. Moreover, nanobarcoding has the potential to be applied to the detection of more than one NP type to study the effects of physicochemical properties, targeting mechanisms, and route of entry on NP biodistribution. The nanobarcoding method was validated in vitro using NB-functionalized superparamagnetic iron oxide NPs (NB-SPIONs) as the model NP type for improved NP detection inside HeLa human cervical cancer cells, a cell line commonly used for ISPCR-mediated detection of human papilloma virus (HPV). Nanotoxicity effects of NB-SPIONs were also evaluated at the single-cell level using LEAP (Laser-Enabled Analysis

  7. Electrophysiological studies in healthy subjects involving caffeine

    OpenAIRE

    Carvalho, Mamede de; Marcelino, Erica; Mendonça, Alexandre de

    2010-01-01

    Copyright ©2012 IOS Press All rights reserved. We review the electrophysiological studies concerning the effects of caffeine on muscle, lower and upper motor neuron excitability and cognition. Several different methods have been used, such as electromyography, recruitment analysis, H-reflex, transcranial magnetic stimulation (TMS), electroencephalography and event-related potentials. The positive effect of caffeine on vigilance, attention, speed of reaction, information processing and arou...

  8. Electrophysiological studies in healthy subjects involving caffeine.

    Science.gov (United States)

    de Carvalho, Mamede; Marcelino, Erica; de Mendonça, Alexandre

    2010-01-01

    We review the electrophysiological studies concerning the effects of caffeine on muscle, lower and upper motor neuron excitability and cognition. Several different methods have been used, such as electromyography, recruitment analysis, H-reflex, transcranial magnetic stimulation (TMS), electroencephalography and event-related potentials. The positive effect of caffeine on vigilance, attention, speed of reaction, information processing and arousal is supported by a number of electrophysiological studies. The evidence in favor of an increased muscle fiber resistance is not definitive, but higher or lower motor neuron excitability can occur as a consequence of a greater excitation of the descending input from the brainstem and upper motor neurons. TMS can address the influence of caffeine on the upper motor neuron. Previous studies showed that cortico-motor threshold and intracortical excitatory and inhibitory pathways are not influenced by caffeine. Nonetheless, our results indicate that cortical silent period (CSP) is reduced in resting muscles after caffeine consumption, when stimulating the motor cortex with intensities slightly above threshold. We present new data demonstrating that this effect is also observed in fatigued muscle. We conclude that CSP can be considered a surrogate marker of the effect of caffeine in the brain, in particular of its central ergogenic effect.

  9. A Phase 1 biodistribution study of p-boronophenylalanine

    International Nuclear Information System (INIS)

    Coderre, J.A.

    1991-01-01

    The objectives of the Phase I BPA biodistribution study are as follows: Objective 1: To establish the safety of orally administered boronophenylalanine (BPA) as determined by monitoring of patient's vital signs and by clinical analysis of blood before and after BPA administration. Objective 2: To establish BPA pharmacokinetics by monitoring the rates of boron absorption into and clearance from the blood and the rate of urinary excretion of boron. Objective 3: To measure the amount of boron incorporated into human tumors (melanoma, glioma, and breast carcinoma) using samples obtained at surgery or biopsy. This report presents the results obtained from the first thirteen patients entered into the study. Three additional glioblastoma patients have been studied recently at Stony Brook, the tissues are still being analyzed

  10. Lyme carditis. Electrophysiologic and histopathologic study

    International Nuclear Information System (INIS)

    Reznick, J.W.; Braunstein, D.B.; Walsh, R.L.; Smith, C.R.; Wolfson, P.M.; Gierke, L.W.; Gorelkin, L.; Chandler, F.W.

    1986-01-01

    To further define the nature of Lyme carditis, electrophysiologic study and endomyocardial biopsy were performed in a patient with Lyme disease, whose principal cardiac manifestation was high-degree atrioventricular block. Intracardiac recording demonstrated supra-Hisian block and complete absence of an escape mechanism. Gallium 67 scanning demonstrated myocardial uptake, and right ventricular endomyocardial biopsy revealed active lymphocytic myocarditis. A structure compatible with a spirochetal organism was demonstrated in one biopsy specimen. It is concluded that Lyme disease can produce active myocarditis, as suggested by gallium 67 imaging and confirmed by endomyocardial biopsy. Furthermore, the presence of high-grade atrioventricular block in this disease requires aggressive management with temporary pacemaker and corticosteroid therapy

  11. 125I-β-CIT biodistribution study in animals

    International Nuclear Information System (INIS)

    Hu Ping

    2000-01-01

    The purpose is to study the preparation and biodistribution in animal of dopamine transporter imaging agent 125 I-β-CIT. β-CIT was 125 I radioiodinated with Iodogen method, the dynamic distribution of 125 I-β-CIT in brain and critical organs were studied with SD rat (autoradiography) and NIH mice respectively. The radiolabelling yield of 125 I-β-CIT was 84%, the radiochemical purity was better than 98%. Blood clearance could be explained by two-compartment model with a duration of 12h, (α = 3.87, T 1/2α = 0.179, β = 0.162, T 1/2β = 4.276) and three-compartment model in 24 h, (Pi = 5.28, T 1/2Pi = 0.131, α = 0.403, T 1/2α = 1.719, β 0.040, T 1/2β = 17.298). The maxim uptake rate of brain (9.1% +- 1.0%) was reaches at 1h, while at 24h, the target/noise ratio was higher . Critical organs liver, lung, spleen and kidney had high uptake rate [(9.88 +- 1.43) - (16.29 +- 1.72)], except liver, other organs showed quick clearance (T 1/2 125 I-β-CIT has a high striatum uptake and good stability in vivo, can provide good SPECT images, the best acquisition time of SPECT may be about 20h after i.v

  12. Normal Values for Heart Electrophysiology Parameters of Healthy Swine Determined on Electrophysiology Study.

    Science.gov (United States)

    Noszczyk-Nowak, Agnieszka; Cepiel, Alicja; Janiszewski, Adrian; Pasławski, Robert; Gajek, Jacek; Pasławska, Urszula; Nicpoń, Józef

    2016-01-01

    Swine are a well-recognized animal model for human cardiovascular diseases. Despite the widespread use of porcine model in experimental electrophysiology, still no reference values for intracardiac electrical activity and conduction parameters determined during an invasive electrophysiology study (EPS) have been developed in this species thus far. The aim of the study was to develop a set of normal values for intracardiac electrical activity and conduction parameters determined during an invasive EPS of swine. The study included 36 healthy domestic swine (24-40 kg body weight). EPS was performed under a general anesthesia with midazolam, propofol and isoflurane. The reference values for intracardiac electrical activity and conduction parameters were calculated as arithmetic means ± 2 standard deviations. The reference values were determined for AH, HV and PA intervals, interatrial conduction time at its own and imposed rhythm, sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), anterograde and retrograde Wenckebach points, atrial, atrioventricular node and ventricular refractory periods. No significant correlations were found between body weight and heart rate of the examined pigs and their electrophysiological parameters. The hereby presented reference values can be helpful in comparing the results of various studies, as well as in more accurately estimating the values of electrophysiological parameters that can be expected in a given experiment.

  13. Preparation and biodistribution study of 99Tcm labelled dextran conjugates

    International Nuclear Information System (INIS)

    Yang Chunhui; Li Hongyu; Liang Jixin; Lu Jia; Luo Hongyi; Zheng Deqiang; Sun Guiquan

    2012-01-01

    99 Tc m Mannosylated dextran conjugates were prepared through [ 99 Tc m (CO) 3 ] + precursor synthesized by carbonyl Isolink kit. The labelled conjugates were injected sub-dermally into the rear foots of the mice, and the patent blue solution was injected at the same site 10 min before sacrifice. The mice were killed at 1 h and 4 h postinjection, and the samples of different tissues including SLN, 2LN, injection site, liver, spleen, blood were dissected and counted. The uptake in terms was calculated. The results of biodistribution demonstrated that the SLN uptakes of radiopharmaceutical (without mannose in the molecules) were rather low and in vivo excretion of these conjugates were comparatively faster, and the uptake of injection site was also low; on the other hand, the SLN uptakes of radio pharmaceutical (with mannose in their molecules) were much higher than those of their corresponding dextran conjugates without mannose, but the retention in the injection site of these conjugates increased too. The results indicated that the affinity of mannosyl-dextran conjugates to the receptors on the surface of macrophages in the lymph node. In addition, the different relative molecular mass of dextran conjugates also cause different biodistribution results, the major one had higher SLN uptake, the difference was significant (P 99 Tc m (CO) 3 ] + labelled mannosylated dextran conjugates showed promising properties as SLN imaging agent and worth further investigation. (authors)

  14. Compartmental analysis to predict biodistribution in radiopharmaceutical design studies

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Marina F.; Pujatti, Priscilla B.; Araujo, Elaine B.; Mesquita, Carlos H. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)], e-mail: mflima@ipen.br

    2009-07-01

    The use of compartmental analysis allows the mathematical separation of tissues and organs to determinate the concentration of activity in each fraction of interest. Although the radiochemical purity must observe Pharmacopoeia specification (values upper 95%), very lower contains of free radionuclides could contribute significantly as dose in the neighborhood organs and make tumor up take studies not viable in case of radiopharmaceutical on the basis of labeled peptides. Animal studies with a product of Lutetium-177 labeled Bombesin derivative ({sup 177}Lu-BBNP) developed in IPEN-CNEN/SP and free Lutetium-177 developed in CNEA/EZEIZA was used to show how subtract free {sup 177}Lu contribution over {sup 177}Lu-BBNP to estimate the radiopharmaceutical potential as diagnosis or therapy agent. The first approach of the studies included the knowledge of chemical kinetics and mimetism of the Lutetium and the possible targets of the diagnosis/therapy to choose the possible models to apply over the sampling standard methods used in experimental works. A model with only one physical compartment (whole body) and one chemical compartment ({sup 177}Lu-BBNP) generated with the compartmental analysis protocol ANACOMP showed high differences between experimental and theoretical values over 2.5 hours, in spite of the concentration of activity had been in a good statistics rang of measurement. The values used in this work were residence time from three different kinds of study with free {sup 177}Lu: whole body, average excretion and maximum excretion as a chemical compartment. Activity concentration values as time function in measurements of total whole body and activity measurement in samples of blood with projection to total circulating blood volume with {sup 177}Lu-BBNP. Considering the two sources of data in the same modeling a better consistence was obtained. The next step was the statistic treatment of biodistribution and dosimetry in mice (Balb C) considering three chemical

  15. 131I labeling of tamoxifen and biodistribution studies in rats

    International Nuclear Information System (INIS)

    Biber Muftuler, F.Z.; Unak, P.; Teksoz, S.; Acar, C.; Yolcular, S.; Yuerekli, Y.

    2008-01-01

    Tamoxifen [TAM ([Z]-2-[4-(1,2-diphenyl-1-di-butenyl)-phenoxy]-N,N-dimethylethanamine)] has been used as an antiestrogen drug for treatment and prevention of human breast cancer. Tamoxifen was labeled with 131 I using iodogen as an oxidizing agent. Mass spectroscopy of the cold standard showed that the labeling occurs in ortho position to the phenyl ether position of TAM as expected. Quality control, radiochemical yield and stability were established using the radioelectrophoresis method. The radiolabeled compound maintained its stability throughout working period of 24 h. Scintigraphic imaging was performed and tissue distribution was determined in Albino Wistar rats. According to biodistribution and imaging experiments the radiolabeled compound presented estrogen receptor (ER) specificity and it was uptaken by endometrium as well as breast tissue

  16. Electrophysiological study in neuromuscular junction disorders

    Directory of Open Access Journals (Sweden)

    Ajith Cherian

    2013-01-01

    Full Text Available This review is on ultrastructure and subcellular physiology at normal and abnormal neuromuscular junctions. The clinical and electrophysiological findings in myasthenia gravis, Lambert-Eaton myasthenic syndrome (LEMS, congenital myasthenic syndromes, and botulinum intoxication are discussed. Single fiber electromyography (SFEMG helps to explain the basis of testing neuromuscular junction function by repetitive nerve stimulation (RNS. SFEMG requires skill and patience and its availability is limited to a few centers. For RNS supramaximal stimulation is essential and so is display of the whole waveform of each muscle response at maximum amplitude. The amplitudes of the negative phase of the first and fourth responses are measured from baseline to negative peak, and the percent change of the fourth response compared with the first represents the decrement or increment. A decrement greater than 10% is accepted as abnormal and smooth progression of response amplitude train and reproducibility form the crux. In suspected LEMS the effect of fast rates of stimulation should be determined after RNS response to slow rates of stimulation. Caution is required to avoid misinterpretation of potentiation and pseudofacilitation.

  17. [On the first studies of electrophysiology].

    Science.gov (United States)

    de Micheli, Alfredo

    2011-01-01

    A historical outline of the evolution of electrophysiology from the eighteenth century is shortly presented. Topics concerning the so called animal electricity starting from the observations on descharges of Torpedo fish until Bolognese Galvani's researches on the frogs are exposed. The points of view of their oppositionists also are examined. These ones, leaded by the physicist Alessandro Volta, professor in the University of Pavia, believed that electricity detected by galvanists was not inherent to animal but was due to the action of the metallic conductors present in the circuit: contact electricity. Only towards the middle of the nineteenth century the physicist Carlo Matteucci attained to demonstrate the existente of the real animal electricity in form of injury current. It was possible to determine that quantitatively thanks to the capillary electrometer built in 1872 by the French physicist Gabriel Lippmann. This instrument was used by the English physiologist Waller in order to obtain the primitive electrocardiographic tracings in humans (1887). At beginnings of the twentieth century, the Dutch professor Willem Einthoven, of the University of Leiden, introduced his string galvanometer which permitted to allow the modern electrocardiography. So it was possible to record the electrical potentials of myocardial cells, first in vitro, later in isolated and perfused heart, son after in dog's heart in situ and finally in human heart. Therefore now it is possible to effectuate endocardial and epicardial mappings, indispensable in order to diagnose and treat the cardiac arrhythmias.

  18. Single dose toxicity and biodistribution studies of [{sup 18}F] fluorocholine

    Energy Technology Data Exchange (ETDEWEB)

    Campos, Danielle C.; Santos, Priscilla F., E-mail: dcc@cdtn.br [Universidade Federal de Minas Gereais (INCT-MM/UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina. Instituto Nacional de Ciencia e Tecnologia de Medicina Molecular; Silveira, Marina B.; Ferreira, Soraya Z.; Malamut, Carlos; Silva, Juliana B. da, E-mail: radiofarmacoscdtn@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Unidade de Pesquisa e Producao de Radiofarmacos; Souza, Cristina M.; Campos, Liliane C.; Ferreira, Enio; Araujo, Marina R.; Cassali, Geovanni D., E-mail: cassalig@icb.ufmg.br [Universidade Federal de Minas Gerais (LPC/UFMG), Belo Horizonte, MG (Brazil). Lab. de Patologia Comparada

    2013-07-01

    [{sup 18}F]Fluorocholine ({sup 18}FCH) is a valuable tool for non-invasive diagnosis using positron emission tomography (PET). This radiotracer has been proven to be highly effective in detecting recurrences and staging prostate cancer, diagnoses brain, breast, and esophageal tumors and also hepatocellular carcinoma. The higher uptake of fluorocholine by malignant tumors results from increased choline kinase activity due to accelerated cell multiplication and membrane formation. According to the Brazilian Health Surveillance Agency (ANVISA), radiopharmaceuticals have to be registered before commercialization. The aim of this work was to evaluate single dose toxicity and biodistribution of {sup 18}FCH in mice, since preclinical safety studies are required for register. Experimental procedures were approved by the Ethics Committee on Animal Use (CEUA-IPEN/SP). Single dose toxicity and biodistribution studies were conducted in Swiss mice. No signs of toxicity were observed during clinical trial. No changes in the parameters which were examined, such as: body weight, food consumption, clinical pathology parameters or lesions microscopic were noted. Biodistribution results indicated high physiological tracer uptake in kidney, liver and heart 30 min after injection. Lower activities were recorded in other organs/tissues: pancreas, intestine, spleen, bone, bladder, muscle, brain and blood. Initial preclinical investigations showed no toxic effects of {sup 18}FCH at investigated doses and a biodistribution profile very similar to other reports in literature. This information is essential to support future human trials. (author)

  19. Electrophysiologic studies of neronal activities under ischemia condition.

    Science.gov (United States)

    Huang, Shun-Ho; Wang, Ping-Hsien; Chen, Jia-Jin Jason

    2008-01-01

    Substrate with integrated microelectrode arrays (MEAs) provides an alternative electrophysiological method. With MEAS, one can measure the impedance and elicit electrical stimulation from multiple sites of MEAs to determine the electrophysiological conditions of cells. The aims of this research were to construct an impedance and action potential measurement system for neurons cultured on MEAs for observing the electrophysiological signal transmission in neuronal network during glucose and oxygen deprivation (OGD). An extracellular stimulator producing the biphasic micro-current pulse for neuron stimulation was built in this study. From the time-course recording of impedance, OGD condition effectively induced damage in neurons in vitro. It is known that the results of cell stimulation are affected by electrode impedance, so does the result of neuron cells covered on the electrode can measure the sealing resistance. For extracellular stimulation study, cortical neuronal activity was recorded and the suitable stimulation window was determined. However, the stimulation results were affected by electrode impedance as well as sealing impedance resulting from neuron cells covering the electrode. Further development of surface modification for cultured neuron network should provide a better way for in vitro impedance and electrophysiological measurements.

  20. Retinal dysfunction and refractive errors: an electrophysiological study of children

    Science.gov (United States)

    Flitcroft, D I; Adams, G G W; Robson, A G; Holder, G E

    2005-01-01

    Aims: To evaluate the relation between refractive error and electrophysiological retinal abnormalities in children referred for investigation of reduced vision. Methods: The study group comprised 123 consecutive patients referred over a 14 month period from the paediatric service of Moorfields Eye Hospital for electrophysiological investigation of reduced vision. Subjects were divided into five refractive categories according to their spectacle correction: high myopia (⩽−6D), low myopia (>−6D and ⩽−0.75D), emmetropia (>−0.75 and 1.5D) and ERG abnormalities (18/35 with high astigmatism v 20/88 without, χ2 test, p = 0.002). There was no significant variation in frequency of abnormalities between low myopes, emmetropes, and low hyperopes. The rate of abnormalities was very similar in both high myopes (8/15) and high hyperopes (5/10). Conclusions: High ametropia and astigmatism in children being investigated for poor vision are associated with a higher rate of retinal electrophysiological abnormalities. An increased rate of refractive errors in the presence of retinal pathology is consistent with the hypothesis that the retina is involved in the process of emmetropisation. Electrophysiological testing should be considered in cases of high ametropia in childhood to rule out associated retinal pathology. PMID:15774929

  1. 99mTc complexes of benzimidazole and benzoxazole ligands and their biodistribution studies

    International Nuclear Information System (INIS)

    Kothari, K.; Manju, S.; Pillai, M.R.A.; Rath, N.; Dash, K.C.; Sarma, H.D.

    1997-01-01

    Complexation studies of 2 (2' -hydroxyphenyl)benzimidazole (HPBI) and 2(2' -pyridyl)benzoxazole (PBO) with 99m Tc were carried out. The complexes were characterised by TLC, paper electrophoresis and solvent extraction. The ligand HPBI forms complex in high yield (>90%). Biodistribution studies carried out with 99m Tc-HPBI complex in Swiss Albino mice showed rapid clearance of the complex from blood and excretion of the activity through hepatobiliary system. (author). 2 refs., 1 fig., 3 tabs

  2. Formulation of 68Ga BAPEN kit for myocardial positron emission tomography imaging and biodistribution study

    International Nuclear Information System (INIS)

    Yang, Bo Yeun; Jeong, Jae Min; Kim, Young Joo; Choi, Jae Yeon; Lee, Yun-Sang; Lee, Dong Soo

    2010-01-01

    Introduction: Tris(4,6-dimethoxysalicylaldimine)-N,N'-bis(3-aminopropyl) -N,N'-ethylenediamine (BAPEN), a tris(salicylaldimine) derivative, is a heart positron emission tomography (PET) agent when labeled with 68 Ga. However, its labeling requires complicated and time-consuming procedures. In this study, the authors formulated a new BAPEN kit for convenient 68 Ga labeling. Methods: BAPEN (0.25 mg) kits were prepared by dispensing its solution in 1 M sodium acetate buffer (pH 5.5) into sterile vials and lyophilization. The prepared kits were labeled with generator-eluted 68 Ga in 0.1 N HCl. Stability in human serum was tested. Expiration date was determined by accelerated testing according to US Food and Drug Administration guidelines. A Biodistribution study was performed in normal mice after injection via tail vein. Results: The prepared kits achieved radiolabeling efficiencies in excess of 95% and showed a shelf-life of 98 days at 25 deg. C and 64.3 months at 4 deg. C. 68 Ga-BAPEN was found to be stable in human serum at 37 deg. C for at least 1 h. Furthermore, a biodistribution study revealed high heart uptake (10.8% ID/g, 1 h). Conclusions: The authors developed a BAPEN kit for convenient labeling with 68 Ga. The 68 Ga-BAPEN showed high stability and excellent biodistribution results in normal mice, which is required for myocardial PET imaging.

  3. An update on electrophysiological studies in neuropathy

    DEFF Research Database (Denmark)

    Krarup, Christian

    2003-01-01

    The review concentrates on the use of clinical neurophysiology in peripheral nerve disorders covered in the present issue. It is pertinent to distinguish different types of involvement of fibers in diabetic neuropathy, including the involvement of small and large fibers, to outline the diagnostic...... criteria of inflammatory neuropathies, and to describe the spectrum of peripheral nerve pathophysiology in inherited neuropathies. Painful neuropathies represent a particular challenge to clinical neurophysiology since it is mainly small fibers, which are difficult to study, that are affected....

  4. In vivo studies: comparing the administration via and the impact on the biodistribution of radiopharmaceuticals

    International Nuclear Information System (INIS)

    Pinto, Suyene Rocha; Sarcinelle, Michelle Alvares; Souza Albernaz, Marta de; Silva, Franciana Maria Rosa da; Seabra, Sergio Henrique; Almeida do Nascimento, Patricia; Carvalho, Cosme Leonardo Gomes; Santos-Oliveira, Ralph

    2014-01-01

    The use of in vivo assay to determine the biodistribution and subsequent inter-comparison with human parameters has been used since the dawn of science. The use of this type of test admits the metabolic equity among animals for inter-comparison. Thus, the use of Wistar rats in particular is quite frequent. Regarding routes of administration, there are three ways to test priority: jugular vein, intraocular (eye plexus) and caudal; there is a consensus that these three pathways behave in the same way, or at least very similar. Biodistribution studies of drugs, especially radiopharmaceuticals, have been using randomly any of these pathways believed to be effective in their likeness without worrying about your real analytic equity. In this study, we performed in vivo assay in 8 Wistar rats using 99mTc -labeled Herceptin to review the route of administration on the biodistribution result. Thus, four mice were injected via the intraocular (eye plexus), and four were injected via tail (caudal plexus). The results were quite disparate and call the attention of the scientific community to reassess the protocols for animal experiments, in order to have uniformity and fairness between the data and may represent a test for human inter-comparison of more reliable and trustworthy way

  5. New surface radiolabeling schemes of super paramagnetic iron oxide nanoparticles (SPIONs) for biodistribution studies.

    Science.gov (United States)

    Nallathamby, Prakash D; Mortensen, Ninell P; Palko, Heather A; Malfatti, Mike; Smith, Catherine; Sonnett, James; Doktycz, Mitchel J; Gu, Baohua; Roeder, Ryan K; Wang, Wei; Retterer, Scott T

    2015-04-21

    Nanomaterial based drug delivery systems allow for the independent tuning of the surface chemical and physical properties that affect their biodistribution in vivo and the therapeutic payloads that they are intended to deliver. Additionally, the added therapeutic and diagnostic value of their inherent material properties often provides extra functionality. Iron based nanomaterials with their magnetic properties and easily tailorable surface chemistry are of particular interest as model systems. In this study the core radius of the iron oxide nanoparticles (NPs) was 14.08 ± 3.92 nm while the hydrodynamic radius of the NPs, as determined by Dynamic Light Scattering (DLS), was between 90-110 nm. In this study, different approaches were explored to create radiolabeled NPs that are stable in solution. The NPs were functionalized with polycarboxylate or polyamine surface functional groups. Polycarboxylate functionalized NPs had a zeta potential of -35 mV and polyamine functionalized NPs had a zeta potential of +40 mV. The polycarboxylate functionalized NPs were chosen for in vivo biodistribution studies and hence were radiolabeled with (14)C, with a final activity of 0.097 nCi mg(-1) of NPs. In chronic studies, the biodistribution profile is tracked using low level radiolabeled proxies of the nanoparticles of interest. Conventionally, these radiolabeled proxies are chemically similar but not chemically identical to the non-radiolabeled NPs of interest. This study is novel as different approaches were explored to create radiolabeled NPs that are stable, possess a hydrodynamic radius of <100 nm and most importantly they exhibit an identical surface chemical functionality as their non-radiolabeled counterparts. Identical chemical functionality of the radiolabeled probes to the non-radiolabeled probes was an important consideration to generate statistically similar biodistribution data sets using multiple imaging and detection techniques. The radiolabeling approach

  6. Boron biodistribution study in colorectal liver metastases patients in Argentina

    International Nuclear Information System (INIS)

    Cardoso, J.; Nievas, S.; Pereira, M.; Schwint, A.; Trivillin, V.; Pozzi, E.; Heber, E.; Monti Hughes, A.; Sanchez, P.; Bumaschny, E.; Itoiz, M.; Liberman, S.

    2009-01-01

    Ex-situ BNCT for multifocal unresectable liver metastases employing whole or partial autograft techniques requires knowledge of boron concentrations in healthy liver and metastases following perfusion and immersion in Wisconsin solution (W), the procedure employed for organ preservation during ex-situ irradiation. Measurements of boron concentration in blood, liver and metastases following an intravenous infusion of BPA-F in five colorectal liver metastases patients scheduled for surgery were performed. Tissue samples were evaluated for boron content pre and post perfusion and immersion in W. Complementary histological studies were performed. The data showed a dose-dependent BPA uptake in liver, a boron concentration ratio liver/blood close to 1 and a wide spread in the metastases/liver concentration ratios in the range 0.8-3.6, partially attributable to histological variations between samples. Based on the boron concentrations and dose considerations (liver≤ 15 Gy-Eq and tumor≥40 Gy-Eq) at the RA-3 thermal neutron facility (mean flux of about (6±1)x10 9 n cm -2 s -1 ), ex-situ treatment of liver metastases at RA-3 would be feasible.

  7. Conduction disturbances after TAVR: Electrophysiological studies and pacemaker dependency.

    Science.gov (United States)

    Makki, Nader; Dollery, Jenn; Jones, Danielle; Crestanello, Juan; Lilly, Scott

    Permanent pacemaker (PPM) placement occurs in 5-20% of patients after transcatheter aortic valve replacement (TAVR). Although predictors of pacemaker implantation have been established, features that predispose patients to pacemaker utilization on follow up have not been widely reported. We performed a retrospective review of patients undergoing commercial TAVR between 2011 and 2016. We collated patients that underwent in-hospital PPM implantation and had a follow up of at least 3months. Data abstraction was performed for electrophysiological studies (EPS), pacemaker indication, timing, and device interrogation for pacemaker dependency on follow up. A total of 24 patients received in-hospital PPM post-TAVR (14% of total cohort), and mean follow up was 22months. Indications for PPM included resting complete heart block (CHB; 15/24, 63%), left bundle branch block and abnormal electrophysiological study (EPS; 7/24, 29%), alternating bundle branch block (1/24, 4%) and tachy-brady syndrome (1/24, 4%). Pacemaker dependency (underlying ventricular asystole, complete heart block, or >50% pacing) occurred in 8/24 patients (33%) during follow-up, 7 of whom had resting CHB, and one with CHB invoked during EPS. Pacemaker dependency after TAVR is common among those that exhibited CHB, but not among those with a prolonged HV delay during EPS. Although preliminary, these observations are relevant to management of rhythm disturbances after TAVR, and may inform the practice of EPS-based PPM implantation. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Obesity, Cardiovascular Fitness, and Inhibition Function: An Electrophysiological Study

    Directory of Open Access Journals (Sweden)

    Tai-Fen Song

    2016-07-01

    Full Text Available The purpose of the present study was to examine how obesity and cardiovascular fitness are associated with the inhibition aspect of executive function from behavioral and electrophysiological perspectives. One hundred college students, aged 18 to 25 years, were categorized into four groups of equal size on the basis of body mass index and cardiovascular fitness: a normal-weight and high-fitness (NH group, an obese-weight and high-fitness (OH group, a normal-weight and low-fitness (NL group, and an obese-weight and low-fitness (OL group. Behavioral measures of response time and number of errors, as well as event-related potential (ERP measures of P3 and N1, were assessed during the Stroop Task. The results revealed that, in general, the NH group exhibited shorter response times and larger P3 amplitudes relative to the OH, NL, and OL groups, wherein the OL group exhibited the longest response time in the incongruent condition. No group differences in N1 indices were also revealed. These findings suggest that the status of being both normal weight and having high cardiovascular fitness is associated with better behavioral and later stages of electrophysiological indices of inhibition. However, these benefits in inhibition function would be lost in an individual who is obese or has low cardiovascular fitness, reflecting the importance keeping both normal weight and having high cardiovascular fitness.

  9. Biodistribution studies of 99mTc-labeled myoblasts in a murine model of muscular dystrophy

    International Nuclear Information System (INIS)

    Colombo, F.R.; Torrente, Y.; Casati, R.; Benti, R.; Corti, S.; Salani, S.; D'Angelo, M.G.; DeLiso, A.; Scarlato, G.; Bresolin, N.; Gerundini, P.

    2001-01-01

    The purpose of this study was twofold: first, to evaluate the myoblast labeling of various 99m Tc complexes and to select the complex that best accomplishes this labeling, and second to evaluate the biodistribution of myoblasts labeled with this complex using mice with MDX muscular dystrophy (the murine homologue of Duchenne's muscular dystrophy). The following ligands were used to prepare the corresponding 99m Tc complexes: hexakis-methoxy-isobutyl-isonitrile (MIBI), bis(2-ethoxyethyl)diphosphinoethane (Tf), (RR,SS)-4,8-diaza-3,6,6,9-tetramethyl-undecane-2,10-dione-bisoxime (HM-PAO), bis(N-ethyl)dithiocarbamate (NEt), and bis(N-ethoxy, N-ethyl)dithiocarbamate (NOEt). One million murine myoblasts were incubated for 30-60 minutes with 5 mCi of each of the 99mTc complexes prepared from the above ligands. Viability was assessed by microscopic counting after trypan blue staining, and the radioactivity absorbed in the cells was measured after centrifugation. The compound with the highest uptake in cellular pellets was [ 99m Tc]N-NOEt. The biodistribution of myoblasts labeled with this complex was evaluated after intraaortic injection in dystrophic mice. Such an approach has the potential of effecting widespread gene transfer through the bloodstream to muscles lacking dystrophin

  10. Preparation, quality control and biodistribution studies of [61Cu]-oxinate for PET tumor imaging

    International Nuclear Information System (INIS)

    Jalilian, A.R.; Yousefnia, H.; Garousi, J.; Shafaii, K.; Bolourinovin, F.; Zolghadri, S.; Faghihi, R.

    2009-01-01

    Targeting apoptosis is an interesting issue in molecular imaging and various modalities have been presented. However, recent experiences in nuclear pharmacy demonstrated the application of small tracer molecules is more desired. This work was conducted for production of a radiolabeled copper complex, i.e. Cu-oxinate as a potential PET tracer for apoptosis imaging in oncology. Cu-61 was prepared by natural zinc target irradiation with 22 MeV protons (150 μA) via the nat Zn(p, xn) 61 Cu nuclear reaction with a yield of 3.33 mCi/μAh. In order to obtain the best labeling method, optimization reactions were performed for pH, temperature and concentration followed by solid phase extraction. Biodistribution of the tracer was studied in wild-type and fibrosarcoma bearing mice. Under the optimized conditions, radio-thin-layer chromatography (RTLC) and HPLC showed radiochemical purities of 99.99% and 97% respectively (with a minimum specific activity of 16 Ci/mM). Biodistribution of the tracer in fibrosarcoma bearing mice demonstrated a significant tumor uptake after 3 h. Tumor:blood and tumor:muscle ratios were 2.0 and 6.0 after 3 h, respectively. (authors)

  11. Synthesis of DOTMP and biodistribution and imaging study of 177-Lu-DOTMP

    International Nuclear Information System (INIS)

    Deng Xinrong; Luo Zhifu; Xiang Xueqin; Li Fenglin; Fan Caiyun; Liu Zihua; Ye Zhaoyun; Li Hongyu; Chen Yang; Zhuang Ling

    2012-01-01

    Cyclen (1, 4, 7, 10-tetraazacyclododecane) and H 3 PO 3 was used to synthesis DOTMP (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-Tetraamino methylenephosphonate). 177 Lu was produced by irradiating enriched lutetium oxide ( 176 Lu 2 O 3 ) with thermal neutron flux of 2' × 10 13 n/cm 2 /S in swimming pool reactor (SPR) for 10 days. And then DOTMP was labelled by 177 Lu. The biodistribution of 177 Lu-DOTMP in model mice bearing S180 sarcoma and SPECT imaging in Japanese white rabbit were also carried out. The results showed that the total activity of 177 LuCl 3 solution obtained was 9.19 × 10 5 MBq after corresponding chemical process. According to the optimal condition of the labeling experiment, the labelling efficiency of 177 Lu-DOTMP was 99.4%. The results of biodistribution study indicated that 177 Lu-DOTMP eliminated rapidly from blood and was delivered to target bone. The radioactivity uptake was mainly in bone and less in other viscera. The results of SPECT imaging showed that the radioactivity was accumulated in bladder. 177 Lu-DOTMP was mainly excreted by kidney. The uptake of the activity in the skeleton was observed within 22 h postinjection and it became quite significant at 46 h post injection. It indicated that 177 Lu-DOTMP has good bone targeting and is worthy of further research. (authors)

  12. PEGylated superparamagnetic iron oxide nanoparticles labeled with 68Ga as a PET/MRI contrast agent. A biodistribution study

    International Nuclear Information System (INIS)

    Afsaneh Lahooti; Gruttner, Cordula; Parham Geramifar; Hassan Yousefnia

    2017-01-01

    The purpose of this study is to evaluate the biodistribution of polyethylene glycol (PEG) coated superparamagnetic iron oxide nanoparticles radiolabeled with 68 Ga in normal mice after intravenous administration of this probe. Three mice were sacrificed at specific time intervals. The biodistribution data revealed high uptake by liver and spleen (60.62 and 12.65 %ID/g at 120 min post injection for liver and spleen, respectively). The clearance of other organs was fast. These results suggest that 68 Ga-PEG-SPIONs has magnificent capabilities for applying in (PET-MRI) as a theranostic agent for detection of liver and spleen malignancies. (author)

  13. Anti-cancer, pharmacokinetic and biodistribution studies of cremophor el free alternative paclitaxel formulation.

    Science.gov (United States)

    Jain, Subheet K; Utreja, Puneet; Tiwary, Ashok K; Mahajan, Mohit; Kumar, Nikhil; Roy, Partha

    2014-01-01

    The aim of the present investigation is to determine the in vivo potential of previously developed and optimized Cremophor EL free paclitaxel (CF-PTX) formulation consisting of soya phosphatidylcholine and biosurfactant sodium deoxycholate. CF-PTX was found to have drug loading of 6 mg/ml similar to Cremophor EL based marketed paclitaxel formulation. In the present study, intracellular uptake, repeated dose 28 days sub-acute toxicity, anti-cancer activity, biodistribution and pharmacokinetic studies were conducted to determine in vivo performance of CF-PTX formulation in comparison to marketed paclitaxel formulation. Intracellular uptake of CF-PTX was studied using A549 cells by fluorescence activated cell sorting assay (FACS) and fluorescence microscopy. In vivo anti-cancer activity of CF-PTX was evaluated using Ehrlich ascites carcinoma (EAC) model in mice followed by biodistribution and pharmacokinetic studies. FACS investigation showed that fluorescence marker acridine orange (AO) solution showed only 19.8±1.1% intracellular uptake where as significantly higher uptake was observed in the case of AO loaded CF-PTX formulation (85.4±2.3%). The percentage reduction in tumor volume for CF-PTX (72.5±2.3%) in EAC bearing mice was found to be significantly (p<0.05) higher than marketed formulation (58.6±2.8%) on 14th day of treatment. Pharmacokinetic and biodistribution studies showed sustained plasma concentration of paclitaxel depicted by higher mean residence time (MRT; 18.2±1.8 h) and elimination half life (12.8±0.6 h) with CF-PTX formulation as compared to marketed formulation which showed 4.4±0.2 h MRT and 3.6±0.4 h half life. The results of the present study demonstrated better in vivo performance of CF-PTX and this formulation appears to be a promising carrier for sustained and targeted delivery of paclitaxel.

  14. Electrophysiological and pathological study of focal cortical dysplasia

    International Nuclear Information System (INIS)

    Hodozuka, Akira; Hashizume, Kiyotaka; Hayashi, Yoshimitsu; Tanaka, Tatsuya

    2008-01-01

    Clinical and experimental studies on focal cortical dysplasia (FCD) were carried out. For the experimental study, an experimental FCD model of rats was developed. Twenty Wistar rats at 0-2 days after birth were used for the study. Kainic acid (KA) solution was injected stereotaxically into medial and lateral sites of the sensori-motor cortex. Bipolar electrodes were inserted. The behavior of the rats and electroencephalography (EEG) were recorded using a digital video-EEG monitoring system. After observation periods of 1, 2 and 6 months, the rats were perfused for pathological study. FCD was observed adjacent to the site of KA injection in all rats more than one month after the injection. EEG recording demonstrated focal spike discharges in and around the site of injection. However, clinical seizure was not observed. Pathological studies showed decrease in gamma aminobutyric acid (GABA)-A receptors and increase in GABA-B receptors not only in the lesion but also in perilesional areas. Fifteen surgical cases of FCD with intractable epilepsy were included in the clinical study. Neuro-imaging studies including high-resolution MRI and single photon emission computed tomography (SPECT) were performed. Conventional EEG studies demonstrated focal EEG abnormalities with epileptic phenomena. At surgery, intraoperative electrocorticography (ECoG) was performed in order to localize epileptic foci under neuroleptanalgesia. Fourteen patients showed epileptiform discharges on preresection ECoG. All foci in non-eloquent areas were resected. Pathological studies including immunohistochemical staining were performed, and characteristics of the FCD in relation to EEG findings were analyzed. Electrophysiological examination revealed epileptogenecity not only in the lesions but also in perilesional areas. In the lesions, immunohistochemical studies showed decrease in GABA-A receptors and increase in GABA-B receptors in both the lesions and perilesional areas, but N

  15. Preparation of crotalus venom radiolabeled with technetium99m as a tool for biodistribution study

    International Nuclear Information System (INIS)

    Pujatti, Priscilla Brunelli; Santos, Raquel Gouvea dos; Simal, Carlos Jorge Rodrigues

    2005-01-01

    Technetium- 99m ( 99m Tc) has been the radionuclide of choice for nuclear medicine procedures and experimental research. Because of its optimal nuclear properties, 99m Tc is suitable for high efficiency detection with the advantage of reduced radiological waste. Crotalus venom (CV) has been shown to reduce tumors in clinical studies and tissue distribution studies are very important for clinical use. The goal of this work was to obtain CV labeled with 99m Tc which preserves its biological activity. After labeling, biological activity was assessed by hemolytic activity evaluation. Labeled and crude venom caused indirect hemolysis provided that the incubation medium contained an exogenous source of lecithin. High yield radiolabeled-CV was obtained and biological activity was preserved. The results suggest that 99m Tc-CV can be a useful tool for biodistribution studies. (author)

  16. Biodistribution study of [I-123] ADAM in mice brain using quantitative autoradiography

    International Nuclear Information System (INIS)

    Lin, K.J.; Yen, T.C.; Tzen, K.Y.; Ye, X.X.; Hwang, J.J.; Wey, S.P.; Ting, G.

    2002-01-01

    Aim: Autoradiography with radioluminography is a delicate method to characterize newly developed radiotracers and to apply them to pharmacological studies. Herein, we reported a biodistribution result of [I-123] ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5- iodophenylamine) in mice brain quantitatively using imaging plates. Materials and Methods: 1mCi [I-123] ADAM was injected into male ICR mice through tail veins. Brains were removed at sequential time points ranging from 0.5hr to 4hr after injection. The whole brain was cut into 14mm thick coronal sections using a cyrotome. The sections were thaw-mounted on glass plate and apposed placed on an imaging plate with filter paper standards for 24 hours. Imaging reading was done by a Fuji FLA5000 device. Regions of interest were placed on the globus pallidus, hypothalamus, substantia nigra, raphe nuclei and cerebellum corresponding to the sterotaxic atlas, and the PSL/mm 2 values were measured. The specific binding was expressed as the ratios of (targets - cerebellum) to cerebellum. Results: Autoradiography study of brain showed that the [I-123] ADAM was accumulated at serotonin transporter rich sites, including the olfactory tubercle, globus pallidus, thalamus nuclei, hypothalamus, substantia nigra, interpeduncular nucleus, amygdala and raphe nuclei. Biodistribution of [I-123] ADAM in mice brain using quantitative autoradiography method showed a high specific binding in the substantia nigra and hypothalamus and the time-activity curve peaked at 120 min post-injection. Compatible specific binding result was achieved in the region of hypothalamus as compared with previous study by other group using conventional tissue micro-dissection method (Synapse 38:403-412, 2000). However, higher specific binding was observed in certain small brain regions including substantia nigra, raphe nuclei due to improved spatial resolution of the quantitative autoradiography technique. Conclusion: Our result showed that the

  17. Synthesis and study of the biodistribution of a new molecule labeled by technetium 99M

    International Nuclear Information System (INIS)

    Ben alaya, Monia

    2008-01-01

    Cytectrenes are stable complexes, neutral, low-weight molecular and lipophilic, that's allowing them to be able to cross the intact BBB. These piperidinic molecules are synthesized by atomic exchange between tricarbonyl technetium with the Fe-Cyclopentadienyl fragment. The labelling reaction is carried out classically in oil bath at a temperature of 150 C during one hour. The reaction can be optimized using microwave. The study of the biodistribution in rat of these complexes after there purification shows high cerebral uptake. Cytectrenes can be used as a potential cerebral radiotracers for the early diagnosis of neuropsychiatric diseases. Cytectrene are able to cross the BBB regarding there lipophilicity. These characteristic allow them to cross the membrane of the white cells and to be used us a potential agent for the diagnosis of infection. (Author). 44 refs

  18. Effects of external magnetic field on biodistribution of nanoparticles: A histological study

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Tony [Department of Neurology, Chang Gung University College of Medicine and Memorial Hospital, 199 Tung-Hwa N Rd, Taipei, Taiwan (China); Hua, M.-Y. [Department of Chemical and Material Engineering, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan (China); Chen Jyhping [Department of Chemical and Material Engineering, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan (China); Wei, K.-C. [Department of Neurosurgery, Chang Gung University College of Medicine and Memorial Hospital, 199 Tung-Hwa N Rd, Taipei, Taiwan (China); Jung, S.-M. [Department of Pathology, Chang Gung University College of Medicine and Memorial Hospital, 199 Tung-Hwa N Rd, Taipei, Taiwan (China); Chang, Y.-J. [Department of Neurology, Chang Gung University College of Medicine and Memorial Hospital, 199 Tung-Hwa N Rd, Taipei, Taiwan (China); Jou, M.-J. [Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan (China); Ma, Y.-H. [Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan (China)]. E-mail: yhma@mail.cgu.edu.tw

    2007-04-15

    This study investigates the effect of external magnetic fields on the biodistribution of nanoparticles (NP). A NdFeB magnet of 2.4 kG was externally applied over the left femoral artery or right kidney. The 250 nm dextran-coated Fe{sub 3}O{sub 4} NP was injected via tail vein in healthy rats, and organs were taken 1 or 24 h later. Prussian blue stain revealed that NP were more rapidly retained in the liver and spleen than in the lungs. NP aggregation observed in the kidney and femoral artery after application of external magnets was time dependent. Hollow organs such as the intestine, colon, and urinary bladder retained little NP.

  19. Effects of external magnetic field on biodistribution of nanoparticles: A histological study

    International Nuclear Information System (INIS)

    Wu, Tony; Hua, M.-Y.; Chen Jyhping; Wei, K.-C.; Jung, S.-M.; Chang, Y.-J.; Jou, M.-J.; Ma, Y.-H.

    2007-01-01

    This study investigates the effect of external magnetic fields on the biodistribution of nanoparticles (NP). A NdFeB magnet of 2.4 kG was externally applied over the left femoral artery or right kidney. The 250 nm dextran-coated Fe 3 O 4 NP was injected via tail vein in healthy rats, and organs were taken 1 or 24 h later. Prussian blue stain revealed that NP were more rapidly retained in the liver and spleen than in the lungs. NP aggregation observed in the kidney and femoral artery after application of external magnets was time dependent. Hollow organs such as the intestine, colon, and urinary bladder retained little NP

  20. Phase I biodistribution and pharmacokinetic study of Lewis Y targeting immunoconjugate CMD-193 in patients with advanced epithelial cancers

    International Nuclear Information System (INIS)

    Herbertson, R. A.; Lee, F. T.; Hopkins, W.; Smyth, F. E.; Murone, C.; Tebbutt, N. C.; Micallef, N.; MacFarlane, D. J.; Bellen, J.; Sonnichsen, D. S.; Brechbiel, M. W.; Scott, A. M.; Lee, T. L.

    2009-01-01

    Full text:Background: The Lewis Y (Ley) antigen is a blood-group related antigen expressed in >70% of solid tumours. This study explored the biodistribution and pharmacokinetics of the immunoconjugate CMD-193 (humanized anti-Ley antibody conjugated with calichaemicin) in patients with advanced Ley expressing epithelial cancers. Methods: There were 2 dose cohorts, (1.0mg/m2 and 2.6mg/m2). Primary objectives were to determine biodistribution and pharmacokinetics of CMD-193. The first cycle was labelled with 111In for biodistribution assessment, and subsequent cycles were administered 3 weekly to a maximum of 6 cycles. Tumour targeting was assessed using SPECT imaging, and pharmacokinetic analysis was based on gamma counting (111In-CMD-193) and ELISA (CMD-193 protein). Results: Nine patients were enrolled, and received 1-6 treatment cycles. Biodistribution imaging demonstrated initial blood pooling, followed by markedly increased hepatic uptake by day 2 (which persisted to day 8), and fast blood clearance. This pattern was seen for all patients, with no significant tumour uptake visualised in any patient. The overall T 1 /2 of 111In-CMD-193 complex formation in blood. One patient had partial metabolic response on 18F-FDG-PET. No radiologic responses were observed. Conclusions: CMD-193 demonstrates rapid blood clearance and increased hepatic uptake compared to prior studies of the original non-conjugated antibody. This trial highlights the importance of biodistribution and pharmacodynamic assessment in early phase studies of new biologics in clinical development.

  1. Study of pharmacokinetics and biodistribution of radiolabelled receptor specific peptides in laboratory animals

    International Nuclear Information System (INIS)

    Laznickova, A.; Laznicek, M.; Trejtnar, F.; Maecke, H.R.; Mather, S.J.

    2001-01-01

    Somatostatin analogues labelled with different radionuclides could be employed for visualization or treatment of somatostatin receptor-positive tumours. An octapeptide 111 In [DTPA] octreotide is a synthetic radiolabelled somatostatin analogue which is currently in clinical use for detecting small neuroendocrine tumours and metastases not detectable by conventional means. However, several other somatostatin analogues have been under development and testing. The aim of this study was to radiolabel selected somatostatin receptor-binding octapeptides by different radionuclides and to report the results of their biodistribution in rats. The study was focused on the direct labelling of vapreotide (RC-160) with 99m Tc, on the conjugates of octreotide with DFO (desferrioxamine) for labelling with 67 Ga, and on the conjugates of octreotide and TOC with DOTA (tetraazacyclo-dodecane tetraacetic acid) for labelling with 88 Y. In the present study, 88 Y isotope instead of 90 Y was used as a label as 88 Y exhibits a longer half life of decay and emits gamma radiation which can be much more easily detected in biological samples than beta emission. The labelling of octreotide analogues with metal radionuclides using derived bifunctional chelates was simple, straightforward and consistently resulted in high radiochemical purity of the product. On the other hand, the application of the direct labelling method for labelling of RC-160 with 99m Tc was difficult because all procedures had to be made under nitrogen atmosphere and an attainment of high yield proved to be highly dependent on the accurate observation of reaction conditions. The labelling efficiency makes an immediate use of the radiolabelled RC-160 for biological studies impossible and it is necessary to involve the purification step into the labelling procedure. All radiolabelled receptor specific peptides under study exhibited rapid radioactivity clearance from the blood and most organs and tissues. On the other hand

  2. Biodistribution and stability studies of [18F]Fluoroethylrhodamine B, a potential PET myocardial perfusion agent

    International Nuclear Information System (INIS)

    Gottumukkala, Vijay; Heinrich, Tobias K.; Baker, Amanda; Dunning, Patricia; Fahey, Frederic H.; Treves, S. Ted; Packard, Alan B.

    2010-01-01

    Introduction: Fluorine-18-labeled rhodamine B was developed as a potential positron emission tomography (PET) tracer for the evaluation of myocardial perfusion, but preliminary studies in mice showed no accumulation in the heart suggesting that it was rapidly hydrolyzed in vivo in mice. A study was therefore undertaken to further evaluate this hypothesis. Methods: [ 18 F]Fluoroethylrhodamine B was equilibrated for 2 h at 37 deg. C in human, rat and mouse serum and in phosphate-buffered saline. Samples were removed periodically and assayed by high-performance liquid chromatography. Based on the results of the stability study, microPET imaging and a biodistribution study were carried out in rats. Results: In vitro stability studies demonstrated that [ 18 F]fluoroethylrhodamine B much more stable in rat and human sera than in mouse serum. After 2 h, the compound was >80% intact in rat serum but 18 F-labeled rhodamines should accumulate in the heart. Conclusions: [ 18 F]Fluoroethylrhodamine B is more stable in rat and human sera than it is in mouse serum. This improved stability is demonstrated by the high uptake of the tracer in the rat heart in comparison to the absence of visible uptake in the mouse heart. These observations suggest that 18 F-labeled rhodamines are promising candidates for more extensive evaluation as PET tracers for the evaluation of myocardial perfusion.

  3. Evaluation of fibrinogen-DTPA-99mTc. Biodistribution and imaging studies

    International Nuclear Information System (INIS)

    Lungu, V.; Mihailescu, G.; Fugaru, V.; Preda, A.

    1998-01-01

    Labelling with 99m Tc of fibrinogen, using DTPA anhydride as the bifunctional chelating agent, was studied in animals with venous thrombi. The parameters studied were: i) coupled reaction of 99m Tc with the fibrinogen-DTPA-Sn(II) in lyophilised form; ii) biodistribution studies of fibrinogen- 99m Tc in animals with venous thrombi, and iii) imaging studies by scintigraphic methods. The present study showed that the radiochemical purity of fibrinogen-DTPA- 99m Tc is > 95% for a maximum of 5 mCi (185 MBq) radioactivity of 99m Tc in the 1.5-2 ml volume. Above this level of radioactivity we found a drastic decrease in the radiochemical purity. The radioactivity ratio of the venous thrombi to the blood was 2.32+-0.45. The scintigraphic images showed a significant accumulation of fibrinogen-DTPA- 99m Tc in 1-hour-old thrombi, 1 hour after injection. From this results the diagnostic potential of fibrinogen-DTPA-Sn(II) in kit form was evaluated. (author)

  4. {sup 99m}Tc radiolabeling and biodistribution study of scorpionfish (Scorpaena plumieri) venom in Swiss mice

    Energy Technology Data Exchange (ETDEWEB)

    Soprani, Juliana; Pujatti, Priscilla B.; Santos, Raquel G. dos [Centro de Desenvolvimento da Tecnologia Nuclear(CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Lab. de Radiobiologia]. E-mail: falejs@yahoo.com.br; priscillapujatti@yahoo.com.br; santosr@cdtn.br; Figueiredo, Suely G. de [Universidade Federal do Espirito Santo (UFES), Vitoria, ES (Brazil). Depto. de Ciencias Fisiologicas]. E-mail: suelygf@gmail.com; Simal, Carlos [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina]. E-mail: csimal@brfree.com.br

    2007-07-01

    The use of radiotracers in research of animal venom has been scarce, although it allows an excellent approach to follow the process of biodistribution and kinetics of toxins, and tissue distribution studies are very important for clinical use. Our group has demonstrated that Scorpaena plumieri venom (SP) possess high antitumoral activity and can be a source of template molecules for the development of antitumoral drugs. The purpose of this study was to radiolabel SP with 99mTc and investigate its biodistribution profile. High labeling yield was obtained and the results suggest that [99mTc]SP can be an useful tool for in vivo studies. The analysis indicated that SP is excreted manly by the kidneys with a slow clearance rate. The significant [99mTc]SP uptake in the heart and lungs may explain, at least partially, the pulmonary edema and effect cardiac observed by the envenoming. (author)

  5. Labelling of 5-ethyl-5-phenylbarbituric acid with Technetium-99m: biodistribution study in Swiss mice

    International Nuclear Information System (INIS)

    Simoes, Susana B.E.; Oliveira, Marcia B.N. de; Gutfilen, Bianca; Bernardo-Filho, Mario; Alves, Andreia Coelho; Machado-Silva, Jose R.

    1996-01-01

    The 5-ethyl-5-phenylbarbituric acid (phenobarbital) is used as a sedative, hypnotic and anticonvulsant drug. We decided to label it with technetium-99m. In order to determine the optimal conditions, different concentrations of this drug were incubated with various stannous chloride solutions. Then, 99m Tc was added and chromatography was performed using 0.9% NaCl solution, acetone and n-butyl alcohol as the mobile phase. Using a solution of 0.01 mg/ml stannous chloride and 1.0 mg/ml phenobarbital over 92% of the radioactivity bound to phenobarbital 99m Tc-phenobarbital. In the biodistribution study, 99m Tc-phenobarbital was administered in mice intraperitoneal. The main uptake of the labeled drug was in the liver, blood, kidneys, spleen and stomach. The phenobarbital is also used as anesthetic drug in animals. Earlier studies confirm that this drug can dislocate the adult worms of Schistosoma mansoni to mesenteric vein towards the liver and portal vein, so that we used infected animals, radioactivity was not found in isolated worms and we can conclude that the phenobarbital has an indirect action in relation to the displacement of the worms. (author)

  6. Biodistribution study of 153Sm-EDTMP produced by irradiation of natural and enriched Samarium, in rats

    International Nuclear Information System (INIS)

    Meftahi, M.; Bahrami Samani, A.; Babaei, M. H.; Shamsaei Zafarghandi, M.; Ghannadi Maragheh, M.

    2010-01-01

    ''1 53 Sm-EDTMP is one of the well known radiopharmaceuticals for pain palliation of bone metastases. Despite that, it is used just in a few countries. It is due to some reasons like being costly enriched samarium that usually used as target for irradiation and short half-life of 153 Sm. In this investigation, certain amounts of radiopharmaceuticals prepared by irradiation of enriched and natural samarium were injected to some normal rats. Then, the rodents were sacrificed and some of their organs were removed. All of the mentioned stages were performed in order to consider the possibility of exploiting natural samarium instead of enriched samarium by study of biodistribution of both radiopharmaceuticals in various organs especially in bone as the target tissue. At the end, the acceptable results were obtained using natural samarium in comparison with the enriched samarium from the point of view of the biodistribution studies.

  7. Fragmentation, labeling and biodistribution studies of KS1/4, a monoclonal antibody

    International Nuclear Information System (INIS)

    Mohd, S.B.

    1987-01-01

    In this study, an IgG2a (KS1/4), a monoclonal antibody (MoAb) specific against a human lung adenocarcinoma (UCLA P-3) was successfully fragmented enzymatically to yield F(ab') 2 and Fab by using pepsin and papain, respectively. The kinetic of fragmentation of the MoAb was compared to that of human immunoglobulin G (IgG). A similar pattern of fragmentation was observed with both antibodies with a higher percentage yield of the F(ab') 2 and Fab obtained upon the fragmentation of the IgG by the enzymes. The KS1/4 and the two fragments were labeled with three different radionuclides, namely iodine-131, indium-111 and selenium-75. The radioiodination of the MoAb and the fragments was carried out by using a modified chloramine-T method. Radiometal labeling of the MoAb and the fragments with indium-111 was performed by using DTPA as a bifunctional chelating agent, while intrinsic labeling of the MoAb was done by culturing the hybridoma in the presence of 75 Se-methionine. The biodistribution of the radiolabeled MoAb, F(ab') 2 and Fab fragments were performed by injecting the preparations intravenously into nude mice bearing human lung adenocarcinoma

  8. Quantitative neutron capture radiography for studying the biodistribution of tumor-seeking boron-containing compounds

    International Nuclear Information System (INIS)

    Gabel, D.; Holstein, H.; Larsson, B.; Gille, L.; Ericson, G.; Sacker, D.; Som, P.; Fairchild, R.G.

    1987-01-01

    Biodistribution of two compounds presently considered for use in neutron capture therapy has been studied in mice carrying a transplantable Harding-Passey melanoma. A method is described by which quantitative assessment can be made of the boron distribution in whole-body sections of such animals. An alpha-particle-sensitive film is placed in close contact with a freeze-dried section of an animal and exposed to neutrons. The tracks visible after etching are analyzed optoelectronically in fields of 0.6 X 0.6 mm2 and compared to standards of boron homogeneously distributed in liver homogenates. The dynamic range of this method is about two orders of magnitude in concentration, with a lower detection limit of 0.1 to 0.01 ppm 10 B, depending on the rate of induction of spurious tracks by fast neutrons present in the neutron beam chosen. In a transplantable Harding-Passey melanoma in mice, it was found that the sulfhydryl boron hydride Na2B12H11SH presently used for therapy of glioblastoma clears blood, muscle, and brain very rapidly. Its accumulation in tumors was persistent for more than three days. A higher tumor accumulation was observed with its disulfide, which has been suggested for neutron capture therapy. For both compounds, a marked heterogeneity of boron distribution within one tumor was found

  9. Synthesis and preliminary biodistribution studies of [131I]SIB-PEG4-CHC in tumor-bearing mice

    International Nuclear Information System (INIS)

    Xiaobei Zheng; Jing Yang; Xiaojiang Duan; Tingting Niu; Wangsuo Wu; Jianjun Wang; Feng Dong

    2011-01-01

    This work reports the synthesis and preliminary biodistribution results of [ 131 I]SIB-PEG 4 -CHC in tumor-bearing mice. The tributylstannyl precursor ATE-PEG 4 -CHC was synthesized by conjugation of ATE to amino pegylated colchicine NH 2 -PEG 4 -CHC. [ 131 I]SIB-PEG 4 -CHC was radiosynthesized by electrophilic destannylation of the precursor with a yield of ∼44%. The radiochemical purity (RCP) appeared to be >95% by a Sep-Pak cartridge purification. [ 131 I]SIB-PEG 4 -CHC was lipophilic and was stable at room temperature. Biodistribution studies in tumor-bearing mice showed that [ 131 I]SIB-PEG 4 -CHC cleared from background rapidly, and didn't deiodinate in vivo. However, the poor tumor localization excluded it from further investigations as a tumor-targeted radiopharmaceuticals. (author)

  10. Studies of the radiolabeling and biodistribution of substance P using lutetium-177 as a radiotracer

    International Nuclear Information System (INIS)

    Lima, Clarice Maria de

    2011-01-01

    of methionine, using human M059J U-87 MG glioma cells and, showed the effect of oxidation of methionine on the cells binding. Biodistribution studies were performed in Nude mice with tumor model and Balb-c mice. Highest radiochemical purity (> 95%) associated with the highest specific activity of '1 77 Lu-DOTA-SP when the reaction time was 30 minutes, temperature of 90 degree C, 10 gμ of DOTA-SP, and the activity of 177 Lu of 185 MBq. The radiolabeled SP in optimized conditions remained stable at 2-8 degree C and in human serum for 4 hours. In vitro studies showed the binding to cell receptors and this binding was reduced when the peptide was presented in its oxidized form. The addition of methionine combined with gentisic acid prevented the oxidation of peptide and increased the stability of the labeled compound, particularly with high activity of 177 Lu, when using larger mass of DOTA-SP. In vivo studies results showed a favorable biodistribution kinetics of the compound and ability to bind to tumor cells. 177 Lu-DOTA-SP can be a useful tool for in vivo studies due to ease preparation, high stability and affinity for tumor cells. (author)

  11. Comparative study of two different Bombesin derivates labeled with 111In and biodistribution in normal mice

    International Nuclear Information System (INIS)

    Oliveira, Ricardo S.; Alcarde, Lais F.; Correa, Beatriz L.; Massicano, Adriana V.F.; Couto, Renata M.; Mengatti, Jair; Araujo, Elaine B. de

    2013-01-01

    Nuclear medicine is a medical speciality that uses radioactive compounds (radiopharmaceuticals), consisting of a substrate and a radioactive isotope, for diagnostic. Among the peptides of interest for Nuclear Medicine, bombesin (BBN), a 14 amino acid neuropeptide analog of human gastrin-releasing peptide, is one of the highlights. This is a comparative study aiming to establish the best condition to radiolabel two BBN derivatives, (DTPA-Phe-Gly 5 -BBN (6-14) ) and (DTPA-Phe-Gly 2 -BBN (6-14 )) with 111-indium. Specific objectives of this study were evaluate a good condition of radiolabelling in search excellent specific activity the bombesin derivatives and determinate the biodistribution in health mice model. Ten micrograms (10μg) of the derivative DTPA-Phe-Gly2-BBN (6-14) was labeled with 18.5 MBq (0.5 mCi) of 111 InCl 3 at 25°C for different times (5, 15 and 30 minutes). The best condition was applied to peptide mass variation (10, 5, 2.5, 1, 0.5, 0.25 and 0.1 μg), keeping all other parameters fixed. Finally, the influence of 111 InCl 3 activity in the radiolabeling process (18.5, 37, 55.5, 74, 185 MBq) was evaluated. The best conditions were repeated for the second derivate, DTPA-Phe-Gly 5 -BBN (6-14 ). The radiochemical purity was assessed by thin layer chromatography (TLC), using 0.2 M EDTA pH 5 as solvent, and high performance liquid chromatography (HPLC) with a C18 column with linear gradient 10% A to 90% A (v/v) (A: 0,1% of TFA in CH3CN; B: 0,1% of TFA in H2O) at a flow rate of 1 mL/minute for 15 minutes. Considering the reaction time, the higher radiochemical purity was obtained when 10μg of the peptide was labeled with 18.5 MBq (0.5 mCi) of 111 In for 15 minutes at 25°C (97.33 ± 0.50%, n=3). In the mass variation study, the best results of radiochemical purity were obtained when 10 μg of the peptide was employed (97.69 ± 0.4%, n = 4). Finally, the maximum specific activity of the radiolabelled peptides was 1.85 MBq/ μg. The maximum specific

  12. Study on biodistribution and imaging of radioiodinated antisense oligonucleotides in nude mice bearing human lymphoma

    International Nuclear Information System (INIS)

    Wang, R.F.; Shen, J.; Zhang, C.L.; Liu, M.; Guo, F.Q.

    2005-01-01

    The incidence of sporadic lymphoma has risen due to an increase in immunosuppressed patients, particularly those with human immunodeficiency virus (HIV) infection. Sometimes suspect lymphoma has an undetectable location and we can not get the pathological specimen. Management of lymphoma is also difficult because the persistence of a significant number of residual tumor cells after intensive treatment. These relative failures can be attributed to make us choose this study for opening a new diagnostic and therapeutic field of lymphoma from molecular level. Immunoglobulin (Ig) heavy chain framework region (FR) of V1 family have been verified to be a major determinant of malignant phenotype of V1 family B-cell lymphoma. Most of targets for tumor antisense therapy study are protooncogenes, such as c-myc, bc1-2, which are broad -spectrum tumor imaging agents. The aim of this study was to investigate the possibility of using radioiodine labeled FR antisense oligonucleotides (ASONs) as an imaging agent or antisense therapeutic radiopharmaceutical in lymphoma. A 18-mer partial phosphorothioate oligonucleotide sequence was synthesized and grafted in 5 ' with a tyramine group which was further labeled with 125 I or 131 I using the chloramine T method. Normal CD-1 mice were injected via a tail vein with 148 kBq of 125 I-FR-ASON (2∼3 μ g). Animals were sacrificed at 1, 2, 4 and 24 h and tissue samples were studied. Liposome-mediated 3.33 MBq of 131 I-FR-ASON (7 ∼ 9μ g) was injected intratumorally into tumor-bearing BALB/c mice (6 weeks after inoculation of 10 7 Namalwa cells) meanwhile liposome-mediated 131 I labeled sense oligonucleotides served as controls. Biodistribution was monitored by sequential scintigraphy and organ radioactivity measurement 24 h after injection. The percentage of the injected dose per gram (%ID/g) of tumor and tumor/ non-tumor tissue ratios (T/NT) were calculated for each group of mice and the difference between two groups was assessed. The 5

  13. A study on the synthesis, labeling and its biodistribution of estradiol derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Wook; Yang, Seung Dae; Suh, Yong Sup [College of Medicine, Dongguk Univ., Seoul (Korea, Republic of)] [and others

    2000-10-01

    Due to the heterogeneous receptor distribution and changes of receptor status over time, the biochemical measurement of estrogen receptor status of biopsy specimens is not sufficient to diagnose breast cancer. As a result, I-123 labeled estradiols have been applied for the diagnosis. The purpose of this study was to develop a suitable radioligand for imaging estrogen receptor-positive human breast tumors. Among the various estradiol derivatives, 17{alpha}-[{sup 123}I]iodovinyl estradiol ([{sup 123}]IVE) has been prepared from 17{alpha}-ethynyl estradiol. Labeling of E-17{alpha}-[{sup 123}I]iodovinyl estradiol ([{sup 123}]IVE] was carried out using peracetic acid with [{sup 123}I]Nal and Z-[{sup 123}I]IVE labelling was archived using chloamine T/HCL solution with [{sup 123}I]Nal. Labeling yield was determined by silica thin-layer chromatography (TLC) and radiochemical purity was measured by high performance liquid chromatography (HPLC). The biodistribution of E-[{sup 123}I]IVE was measured in immature female rats at 60 min, 120 min and 300 min after injection. The labeling yield of two isomers was 92% and 94% (E-[{sup 123}I]IVE and Z-[{sup 123}I]IVE, respectively). The radiochemical purity was more than 98% after purification. The highest uptake was observed at 120 min in uterus (3.11% ID/g for E-[{sup 123}I]IVE. These results suggest the possibility of using E-[{sup 123}I]IVE as an imaging agent for the evaluation of the presence of estrogen receptor in patients with breast cancer.

  14. A study on the synthesis, labeling and its biodistribution of estradiol derivatives

    International Nuclear Information System (INIS)

    Kim, Sang Wook; Yang, Seung Dae; Suh, Yong Sup

    2000-01-01

    Due to the heterogeneous receptor distribution and changes of receptor status over time, the biochemical measurement of estrogen receptor status of biopsy specimens is not sufficient to diagnose breast cancer. As a result, I-123 labeled estradiols have been applied for the diagnosis. The purpose of this study was to develop a suitable radioligand for imaging estrogen receptor-positive human breast tumors. Among the various estradiol derivatives, 17α-[ 123 I]iodovinyl estradiol ([ 123 ]IVE) has been prepared from 17α-ethynyl estradiol. Labeling of E-17α-[ 123 I]iodovinyl estradiol ([ 123 ]IVE] was carried out using peracetic acid with [ 123 I]Nal and Z-[ 123 I]IVE labelling was archived using chloamine T/HCL solution with [ 123 I]Nal. Labeling yield was determined by silica thin-layer chromatography (TLC) and radiochemical purity was measured by high performance liquid chromatography (HPLC). The biodistribution of E-[ 123 I]IVE was measured in immature female rats at 60 min, 120 min and 300 min after injection. The labeling yield of two isomers was 92% and 94% (E-[ 123 I]IVE and Z-[ 123 I]IVE, respectively). The radiochemical purity was more than 98% after purification. The highest uptake was observed at 120 min in uterus (3.11% ID/g for E-[ 123 I]IVE. These results suggest the possibility of using E-[ 123 I]IVE as an imaging agent for the evaluation of the presence of estrogen receptor in patients with breast cancer

  15. Electrophysiologic studies of the thoracic limb of the horse.

    Science.gov (United States)

    Blythe, L L; Kitchell, R L

    1982-09-01

    The cutaneous innervation of the thoracic limb was investigated in 18 barbiturate-anesthetized horses, using electrophysiologic techniques. The cutaneous area (CA) innervated by each cutaneous nerve was delineated in at least 4 horses by stroking the hairs with a small watercolor brush while recording from the nerve. Mapping of adjacent CA revealed areas of considerable overlap. The part of a CA of a given nerve supplied only by that nerve is referred to as its autonomous zone (AZ). In contrast to the standard textbook illustrations cutaneous branches of the axillary, radial, musculocutaneous, and ulnar nerves overlapped extensively in the antebrachium. Clinically testable AZ were found in the antebrachium for the caudal cutaneous antebrachial nerve of the ulnar nerve and in the carpus and manus for the cutaneous branches of the median, ulnar, and musculocutaneous nerves; AZ were not found for the cutaneous branches of the radial and axillary nerves.

  16. A study of computational dosimetry and boron biodistribution for ex – situ lung BNCT at RA-3 Reactor

    International Nuclear Information System (INIS)

    Garabalino, M.A.; Trivillin, V. A.; Monti Hughes, A.; Pozzi, E.C.C.; Thorp, S.; Curotto, P; Miller, M.; Santa Cruz, G.A.; Saint Martin, G.; Schwint, A.E.; González, S.J.; Farías, R.O; Portu, A.; Ferraris, S.; Santa María, J.; Lange, F.; Bortolussi, S.; Altieri, S.

    2013-01-01

    Within the context of the preclinical ex-situ BNCT Project for the treatment of diffuse lung metastases, we performed boron biodistribution studies in a sheep model and computational dosimetry studies in human lung to evaluate the potential therapeutic efficacy of the proposed technique. Herein we report preliminary data that supports the use of the sheep model as an adequate human surrogate in terms of boron kinetics and uptake in clinically relevant tissues. Furthermore, the estimation of the potential therapeutic efficacy of the proposed treatment in humans, based on boron uptake values in the large animal model, yields promising tumor control probability values even in the most conservative scenario considered. (author)

  17. Poly(n-butylcyanoacrylate nanoparticles for oral delivery of quercetin: preparation, characterization, and pharmacokinetics and biodistribution studies in Wistar rats

    Directory of Open Access Journals (Sweden)

    Bagad M

    2015-06-01

    Full Text Available Mayur Bagad, Zaved Ahmed KhanMedical Biotechnology Division, School of Biosciences and Technology, VIT University, Vellore Tamil Nadu, IndiaBackground: Quercetin (QT is a potential bioflavonol and antioxidant with poor bioavailability and very low distribution in the brain. A new oral delivery system comprising of poly(n-butylcyanoacrylate nanoparticles (PBCA NPs was introduced to improve the oral bioavailability of QT and to increase its distribution in the brain. Physicochemical characteristics, in vitro release, stability in simulated gastric fluid and intestinal fluids, and pharmacokinetics and biodistribution studies of QT-PBCA NPs coated with polysorbate-80 (P-80 were investigated.Objective: This study aimed to investigate the physicochemical characteristics, in vitro release, stability in simulated gastric fluid and intestinal fluids, and pharmacokinetics and biodistribution studies of QT-PBCA NPs coated with polysorbate-80 (P-80.Results: The results showed that QT-PBCA NPs and QT-PBCA NPs coated with P-80 (QT-PBCA+P-80 had mean particle sizes of 161.1±0.44 nm and 166.6±0.33 nm respectively, and appeared spherical in shape under transmission electron microscopy. The mean entrapment efficiency was 79.86%±0.45% for QT-PBCA NPs and 74.58%±1.44% for QT-PBCA+P-80. The in vitro release of QT-PBCA NPs and QT-PBCA+P-80 showed an initial burst release followed by a sustained release when compared to free QT. The relative bioavailability of QT-PBCA NPs and QT-PBCA+P-80 enhanced QT bioavailability by 2.38- and 4.93-fold respectively, when compared to free QT. The biodistribution study in rats showed that a higher concentration of QT was detected in the brain after the NPs were coated with P-80.Conclusion: This study indicates that PBCA NPs coated with P-80 can be potential drug carriers for poorly water-soluble drugs. These NPs were observed to improve the drugs’ oral bioavailability and enhance their transport to the brain

  18. Direct comparison of radiation dosimetry of six PET tracers using human whole-body imaging and murine biodistribution studies

    International Nuclear Information System (INIS)

    Sakata, Muneyuki; Oda, Keiichi; Toyohara, Jun; Ishii, Kenji; Nariai, Tadashi; Ishiwata, Kiichi

    2013-01-01

    We investigated the whole-body biodistributions and radiation dosimetry of five 11 C-labeled and one 18 F-labeled radiotracers in human subjects, and compared the results to those obtained from murine biodistribution studies. The radiotracers investigated were 11 C-SA4503, 11 C-MPDX, 11 C-TMSX, 11 C-CHIBA-1001, 11 C-4DST, and 18 F-FBPA. Dynamic whole-body positron emission tomography (PET) was performed in three human subjects after a single bolus injection of each radiotracer. Emission scans were collected in two-dimensional mode in five bed positions. Regions of interest were placed over organs identified in reconstructed PET images. The OLINDA program was used to estimate radiation doses from the number of disintegrations of these source organs. These results were compared with the predicted human radiation doses on the basis of biodistribution data obtained from mice by dissection. The ratios of estimated effective doses from the human-derived data to those from the mouse-derived data ranged from 0.86 to 1.88. The critical organs that received the highest absorbed doses in the human- and mouse-derived studies differed for two of the six radiotracers. The differences between the human- and mouse-derived dosimetry involved not only the species differences, including faster systemic circulation of mice and differences in the metabolism, but also measurement methodologies. Although the mouse-derived effective doses were roughly comparable to the human-derived doses in most cases, considerable differences were found for critical organ dose estimates and pharmacokinetics in certain cases. Whole-body imaging for investigation of radiation dosimetry is desirable for the initial clinical evaluation of new PET probes prior to their application in subsequent clinical investigations. (author)

  19. Iron-EHPG as an hepatobiliary MR contrast agent: initial imaging and biodistribution studies

    International Nuclear Information System (INIS)

    Lauffer, R.B.; Greif, W.L.; Stark, D.D.; Vincent, A.C.; Saini, S.; Wedeen, V.J.; Brady, T.J.

    1988-01-01

    A paramagnetic relaxation agent targeted to functioning hepatocytes of the liver and excreted into the bile would be useful in the enhancement of normal liver and biliary anatomy in MR imaging. We sought to demonstrate the feasibility of this approach using the prototype hepatobiliary MR contrast agent, iron(III) ethylenebis-(2-hydroxyphenylglycine) (Fe(EHPG) - ). The biodistribution, relaxation enhancement, and imaging characteristics of Fe(EHPG) - were compared to those of the non-specific iron chelate iron(III) diethylenetriaminepentaacetic acid (Fe(DTPA) 2- ), which has a comparable effect on water proton relaxation times. (author)

  20. The synthesis of a new cardiac sympathetic nerve imaging agent N-[11C]CH3-dopamine and biodistribution study

    International Nuclear Information System (INIS)

    Yulin He; Weina Zhou; Xiangcheng Wang; Baoliang Bao; Guojian Zhang; Cheng Wang; Chunmei Wang; Xuemei Wang; Wei Fang

    2014-01-01

    In this study, we synthesized and characterized N-[ 11 C]methyl-dopamine ([ 11 C]MDA) for cardiac sympathetic nerve imaging. [ 11 C]MDA was synthesized by direct N-methylation of dopamine with [ 11 C]methyl iodide and purified by semi-preparation reverse high pressure liquid chromatography (HPLC). The total synthesis time was 45 min including HPLC purification. The radiochemical yields of [ 11 C]MDA was 20 ± 3 %, without decay correction. The radiochemical purity was >98 % and the specific activity was about 50 GBq/mmol. The biological properties of [ 11 C]MDA were evaluated by biodistribution study in normal mice. PET imaging was performed in healthy Chinese mini-swines. Biodistribution study showed that [ 11 C]MDA had high myocardium uptake. PET/CT imaging showed [ 11 C]MDA had clear and symmetrical myocardium uptake, which was blocked obviously by injecting imipramine hydrochloride. [ 11 C]MDA would be a promising candidate of radiotracer for cardiac sympathetic nervous system imaging. (author)

  1. Comparative study on biodistribution of domestic and imported 125I-β-CIT

    International Nuclear Information System (INIS)

    Liu Xingdang; Lin Xiangtong; Fang Ping; Chen Zhengping; Zhou Xiang; Wang Bocheng; Zhang Manda

    2003-01-01

    Objective: To characterize the kinetics and biodistribution of a domestically synthesized 125 I-2β-carbomethoxy-3β-4-iodopheny1tropane (β-CIT ) and to compare it with that of 125 I-β-CIT imported from RBI company. Methods: 1)The biodistribution of domestic and RBI company produced 125 I-β-CIT in KM mice. Twenty groups of mice (group of 5) were injected into the tail vein with either one of 125 I-β-CIT products. Each group of both products was killed at 5,15,30 and 45 min, and 1, 2, 4, 6, 8 and 24 h. 2)Autoradiography was performed on the brain of SD rats at 2 h after injection. Results: Domestic 125 I-β-CIT was primarily uptaked in the striatum, also in areas rich in 5-HTT such as the brain stem, frontal cortex, parietal cortex, temporal cortex, occipital cortex and hippocampus. Striatal uptake peaked at 2 h postinjection of 125 I-β-CIT. The ratio of specific to nonspecific binding in striatum peaked at 6 h. The highest radioactivity was in the lungs and the less radioactivity was in the liver, kidney, spleen and intestine. Autoradiography confirmed that 125 I-β-CIT primarily bound to striatum and lower room temperature significantly reduced the binding of the agent. Conclusion: The domestic 125 I-β-CIT binds primarily to dopamine transporters in the striatum in mice and rats and the maximum uptake is in the lungs

  2. 99m Tc-tazobactam, a novel infection imaging agent: Radiosynthesis, quality control, biodistribution, and infection imaging studies.

    Science.gov (United States)

    Rasheed, Rashid; Naqvi, Syed Ali Raza; Gillani, Syed Jawad Hussain; Zahoor, Ameer Fawad; Jielani, Asif; Saeed, Nidda

    2017-05-15

    The radiolabeled drug 99m Tc-tazobactam ( 99m Tc-TZB) was developed and assessed as an infection imaging agent in Pseudomonas aeruginosa and Salmonella enterica infection-induced animal models by comparing with inflammation induced animal models. Radiosynthesis of 99m Tc-TZB was assessed while changing ligand concentration, reducing agent concentration, pH, and reaction time while keeping radioactivity constant (~370 MBq). Percent labeling of the resulting complex was measured using paper chromatography and instant thin layer chromatography. The analysis of the 99m Tc-TZB complex indicated >95% labeling yield and electrophoresis revealed complex is neutral in nature. The biodistribution study also showed predominantly renal excretion; however liver, stomach, and intestine also showed slight tracer agent uptake. The agent significantly accumulated in Pseudomonas aeruginosa and Salmonella enterica infection induced tissues 3.58 ± 0.26% and 2.43 ± 0.42% respectively at 1 hour postinjection. The inflamed tissue failed to uptake noticeable activity at 1 hour time point. The scintigraphic study results were found in accordance with biodistribution pattern. On the basis of our preliminary results, the newly developed 99m Tc-TZB can be used to diagnose bacterial infection and to discriminate between infected and inflamed tissues. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Biodistribution and pharmacokinetic studies of a porphyrin dimer photosensitizer (Oxdime) by fluorescence imaging and spectroscopy in mice bearing xenograft tumors.

    Science.gov (United States)

    Khurana, Mamta; Ulrich, Sébastien; Kim, Anthony; Moriyama, Yumi; Netchev, George; Akens, Margarete K; Anderson, Harry L; Wilson, Brian C

    2012-01-01

    Herein, we present a study of the pharmacokinetics and biodistribution of a butadiyne-linked conjugated porphyrin dimer (Oxdime) designed to have high near-infrared (NIR) 2-photon absorption cross-section for photodynamic therapy (PDT). Changes in biodistribution over time were monitored in mice carrying B16-F10 melanoma xenografts, following intravenous injection. Using fluorescence imaging of live animals and analyzing isolated organs ex vivo at different time points between 30 min and 24 h after injection, accumulation of Oxdime was measured in several organs (heart, kidney and liver) and in tumor. The concentration in the plasma was about 5-10 times higher than in other tissues. The fluorescence signal peaked at 3-12 h after injection in most tissues, including the tumor and the plasma. The change in the fluorescence emission spectrum of the sensitizer over time was also monitored and a shift in the maximum from 800 to 740 nm was observed over 24 h, showing that the Oxdime is metabolized. Significant quantities accumulated in the tumor, indicating that this PDT sensitizer may be promising for cancer treatment. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

  4. Biodistribution studies of {sup 99m}Tc-labeled myoblasts in a murine model of muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Colombo, F.R. E-mail: colombof@policlinico.mi.it; Torrente, Y.; Casati, R.; Benti, R.; Corti, S.; Salani, S.; D' Angelo, M.G.; DeLiso, A.; Scarlato, G.; Bresolin, N.; Gerundini, P

    2001-11-01

    The purpose of this study was twofold: first, to evaluate the myoblast labeling of various {sup 99m}Tc complexes and to select the complex that best accomplishes this labeling, and second to evaluate the biodistribution of myoblasts labeled with this complex using mice with MDX muscular dystrophy (the murine homologue of Duchenne's muscular dystrophy). The following ligands were used to prepare the corresponding {sup 99m}Tc complexes: hexakis-methoxy-isobutyl-isonitrile (MIBI), bis(2-ethoxyethyl)diphosphinoethane (Tf), (RR,SS)-4,8-diaza-3,6,6,9-tetramethyl-undecane-2,10-dione-bisoxime (HM-PAO), bis(N-ethyl)dithiocarbamate (NEt), and bis(N-ethoxy, N-ethyl)dithiocarbamate (NOEt). One million murine myoblasts were incubated for 30-60 minutes with 5 mCi of each of the 99mTc complexes prepared from the above ligands. Viability was assessed by microscopic counting after trypan blue staining, and the radioactivity absorbed in the cells was measured after centrifugation. The compound with the highest uptake in cellular pellets was [{sup 99m}Tc]N-NOEt. The biodistribution of myoblasts labeled with this complex was evaluated after intraaortic injection in dystrophic mice. Such an approach has the potential of effecting widespread gene transfer through the bloodstream to muscles lacking dystrophin.

  5. Study of biodistribution properties of a new myocardial imaging agent 99Tcm-N-DBODC5

    International Nuclear Information System (INIS)

    Zhang Wanchun; Fang Wei; Wang Feng; Guo Feng; Guo Lin; He Zuoxiang; Wang Xuebin; Lin Bin; Tang Zhigang

    2007-01-01

    99 Tc m -N-DBODC5 for intravenous injection was prepared. The labelling yield was 95.0% ± 0.52%. Sixteen New Zealand rabbits were involved and planar gamma imaging was performed at 10 time-point after injection of 99 Tc m -N-DBODC5. The radioactivity changes of organs were calculated by regions of interest (ROI) analysis. The 16 rabbits were divided into 4 groups and were sacrificed at 30, 60, 120, and 180 min after iniection respectively. The activity for all excised organs were measured by γ-well counting for calculating radiouptake. Myocardial uptake for 99 Tc m -N-DBODC5 is high. Though myocardial uptake was lower than 99 Tc m -MIBI, the liver clearance for 99 Tc m -N-DBODC5 was more rapid than that of 99 Tc m MIBI. As early as 30 min after injection, 99 Tc m -N-DBODC5 heart-to-liver ratio is 0.98 ± 0.52 versus 0.56 ± 0.19 for 99 Tc m -MIBI (P 99 Tc m -N-DBODC5 heart-to-liver ratio improved to the peak value (1.18 ± 0.57), compared with 0.71 ± 0.29 for 99 Tc m -MIBI, P 99 Tc m - N-DBODC5 was keeping at a high level until 180 min. 99 Tc m -N-DBODC5 exhibited rapid lung clearance, similar to that of 99 Tc m -MIBI. The biodistribution in the isolated organs demonstrated the same trend. The rapid 99 Tc m -N-DBODC5 liver clearance may allow the earlier imaging, and overcome the photon scatter from the liver with high activity which interfered the inferoapical wall in myocardial images. 99 Tc m -N-DBODC5 is a promising new myocardial perfusion imaging agent with superior biodistribution properties. (authors)

  6. The diagnostic efficacy of clinical findings and electrophysiological studies in carpal tunnel syndrome

    OpenAIRE

    Buyukkoyuncu Pekel, Nilufer; Nar Senol, Pelin; Yildiz, Demet; Kilic, Ahmet Kasim; Kamaci Sener, Deniz; Seferoglu, Meral; Gunes, Aygul

    2017-01-01

    Objective. The aim of the study was to examine the relation between clinical findings, neurological examination and electrophysiological studies in diagnosing carpal tunnel syndrome (CTS) and share our institutional experience in patients with CTS. Methods. Patients presenting with complaints of pain, paresthesia, and weakness in hands who diagnosed CTS between 2014 and 2015 were examined retrospectively. Demographic characteristics, clinical and neurological examination findings and electrod...

  7. Role of Electrophysiological Study and Catheter Ablation for Recurrent Ventricular Tachycardia Complicating Myocarditis

    Directory of Open Access Journals (Sweden)

    Emanuele Cecchi

    2012-01-01

    Full Text Available Here we report the case of a 31-year-old man admitted to our hospital with echocardiografic and Cardiac Magnetic Resonance signs of myocarditis complicated by ventricular tachycardia, initially resolved with direct current shock. After the recurrence of ventricular tachycardia the patient was submitted to electrophysiological study revealing a re-entrant circuit at the level of the medium segment of interventricular septum, successfully treated with transcatheter ablation. This case highlights how the presence of recurrent ventricular arrhythmias at the onset of acute myocarditis, suspected or proven, could be associated with a pre-existing arrhythmogenic substrate, therefore these patients should be submitted to electrophysiological study in order to rule out the presence of arrhythmogenic focuses that can be treated with transcatheter ablation.

  8. Experimental biodistribution studies of 99mTc-recombinant human serum albumin (rHSA): a new generation of radiopharmaceutical

    International Nuclear Information System (INIS)

    Perkins, A.C.; Frier, M.

    1994-01-01

    Recombinant human serum albumin (rHSA) produced by cultured fermentation has been prepared in the form of microcapsules nominally 3-5 μm in diameter and radiolabelled with technetium-99m following reduction with stannous chloride. Radiochemical purity was assessed by chromatography on instant thin-layer chromatography and found to be greater than 90%. No evidence of aggregation was seen by microscopic examination. Imaging biodistribution studies in New Zealand white rabbits demonstrated targeting to the liver or lung, respectively, depending upon the size and surfactant properties of the microcapsules. This communication is the first to show scintigraphic studies using 99m Tc-labelled rHSA with the potential for lung, liver and cardiovascular imaging and demonstrates that recombinant DNA technology offers an important new source of materials suitable for use as radiopharmaceuticals without the need for pooled human blood products. (orig.)

  9. Boron Neutron Capture Therapy (BCNT) for the Treatment of Liver Metastases: Biodistribution Studies of Boron Compounds in an Experimental Model

    Energy Technology Data Exchange (ETDEWEB)

    Marcela A. Garabalino; Andrea Monti Hughes; Ana J. Molinari; Elisa M. Heber; Emiliano C. C. Pozzi; Maria E. Itoiz; Veronica A. Trivillin; Amanda E. Schwint; Jorge E. Cardoso; Lucas L. Colombo; Susana Nievas; David W. Nigg; Romina F. Aromando

    2011-03-01

    Abstract We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of 10B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studies at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na210B10H10), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3.

  10. History of Bioelectrical Study and the Electrophysiology of the Primo Vascular System

    Directory of Open Access Journals (Sweden)

    Sang Hyun Park

    2013-01-01

    Full Text Available Background. Primo vascular system is a new anatomical structure whose research results have reported the possibility of a new circulatory system similar to the blood vascular system and cells. Electrophysiology, which measures and analyzes bioelectrical signals tissues and cells, is an important research area for investigating the function of tissues and cells. The bioelectrical study of the primo vascular system has been reported by using modern techniques since the early 1960s by Bonghan Kim. This paper reviews the research result of the electrophysiological study of the primo vascular system for the discussion of the circulatory function. We hope it would help to study the electrophysiology of the primo vascular system for researchers. This paper will use the following exchangeable expressions: Kyungrak system = Bonghan system = Bonghan circulatory system = primo vascular system = primo system; Bonghan corpuscle = primo node; Bonghan duct = primo vessel. We think that objective descriptions of reviewed papers are more important than unified expressions when citing the papers. That said, this paper will unify the expressions of the primo vascular system.

  11. Electrophysiological studies in thyrotoxicosis with and without associated sick sinus syndrome

    International Nuclear Information System (INIS)

    Talwar, K.K.; Gupta, V.; Kaul, U.; Ahuja, M.M.; Bhatia, M.L.

    1987-01-01

    Electrophysiological studies in 13 patients with thyrotoxicosis (5 men and 8 women, aged 17 to 76 years) are reported. Five patients presented with features of sick sinus syndrome (SSS) (Group A) while the remaining 8 patients (Group B) had no detectable cardiovascular abnormality. Sinus node function (corrected sinus node recovery and sinoatrial conduction time) was abnormal in all Group A but normal in Group B patients. Intra-atrial, artioventricular (AV) nodal, and infranodal conduction time and effective refractory period of atrium were normal in all patients in both groups. Effective refractory period of AV node was decreased in 6 patients (3 in each group). All Group A patients received radioiodine with complete clinical remission of sick sinus state in 4 subjects. Repeat electrophysiological studies in two of these patients, 6 and 12 months after treatment, showed complete normalization of sinus node function. This is the first reported electrophysiological study documenting the occurrence of SSS in thyrotoxicosis reversed by effective antithyroid treatment. We suggest that attempts should be made to identify underlying thyrotoxicosis in all patients with SSS, especially in the older age group. Appropriate medical treatment may prevent unnecessary implantation of permanent pacemakers in such patients

  12. Analyzing the electrophysiological effects of local epicardial temperature in experimental studies with isolated hearts

    International Nuclear Information System (INIS)

    Tormos, Alvaro; Millet, José; Guill, Antonio; Chorro, Francisco J; Cánoves, Joaquín; Mainar, Luis; Such, Luis; Alberola, Antonio; Trapero, Isabel; Such-Miquel, Luis

    2008-01-01

    As a result of their modulating effects upon myocardial electrophysiology, both hypo- and hyperthermia can be used to study the mechanisms that generate or sustain cardiac arrhythmias. The present study describes an original electrode developed with thick-film technology and capable of controlling regional temperature variations in the epicardium while simultaneously registering its electrical activity. In this way, it is possible to measure electrophysiological parameters of the heart at different temperatures. The results obtained with this device in a study with isolated and perfused rabbit hearts are reported. An exploration has been made of the effects of local temperature changes upon the electrophysiological parameters implicated in myocardial conduction. Likewise, an analysis has been made of the influence of local temperature upon ventricular fibrillation activation frequency. It is concluded that both regional hypo- and hyperthermia exert reversible and opposite effects upon myocardial refractoriness and conduction velocity in the altered zone. The ventricular activation wavelength determined during constant pacing at 250 ms cycles is not significantly modified, however. During ventricular fibrillation, the changes in the fibrillatory frequency do not seem to be transmitted to normal temperature zones

  13. Study of biodistribution of lipidic nanospheres charged with cis-diaminedichloroplatinum (II) and labelled with radioactive nuclei of Indium-111

    International Nuclear Information System (INIS)

    Lopez R, V.; Juarez O, C.; Medina L, A.; Perez C, E.; Garcia L, P.

    2007-01-01

    The general objective of the study was to evaluate the lipidic nanospheres biodistribution charged with cis-diaminedichloroplatinum (II) (cis-DDP) and labelled with radioactive nuclei of Indium-111 (Lip-Cis-in-111) in Wistar rats and in a tumoral model of CaCu. The conclusions were: 1. The system Lip-Cis-in-111 it presents a very fast elimination probably, to a fast recognition response of the reticuloendothelial system (RES). 2. It is planned to make modifications to the formulation to increase the quantity of the hydrophilic polymer (PEG), so that its time of residence in the blood is bigger and allow a bigger accumulation in the tumor. (Author)

  14. Iodine-123 labelled nor-beta-CIT binds to the serotonin transporter in vivo as assessed by biodistribution studies in rats

    NARCIS (Netherlands)

    Booij, J.; Knol, R. J.; Reneman, L.; de Bruin, K.; Janssen, A. G.; van Royen, E. A.

    1998-01-01

    Iodine-123 labelled 2beta-carbomethoxy-3beta-4-iodophenylnortropane (nor-beta-CIT), a radioiodinated cocaine analogue, was evaluated as an agent for the in vivo labelling of serotonin transporters by biodistribution studies in rats. Intravenous injection of [123I]nor-beta-CIT resulted in high

  15. Synthesis, characterization, and biodistribution studies of {sup 99m}Tc-labeled SBA-16 mesoporous silica nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Branco de Barros, André Luís [Centro de Desenvolvimento da Tecnologia Nuclear, Belo Horizonte, Minas Gerais (Brazil); Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais (Brazil); Silva de Oliveira Ferraz, Karina; Soares Dantas, Thais Cristina; Ferreira Andrade, Gracielle [Centro de Desenvolvimento da Tecnologia Nuclear, Belo Horizonte, Minas Gerais (Brazil); Nascimento Cardoso, Valbert [Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais (Brazil); Barros de Sousa, Edésia Martins, E-mail: sousaem@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear, Belo Horizonte, Minas Gerais (Brazil)

    2015-11-01

    Along with anti-cancer drug delivery researches, many efforts have been done to develop new tracers for diagnostic applications. Based on advances in molecular imaging, nanoparticles can be used to visualize, characterize and measure biological process at molecular and cellular level. Therefore, the purpose of this study was to synthesize, characterize and radiolabeled mesoporous silica nanoparticles (MSNs) for in vivo applications. The nanoparticles were synthesized, functionalized with 3-aminopropyltriethoxysilane (APTES) and then, anchored with diethylenetriaminepentaacetic acid (DTPA). Particles were physicochemical characterized by elemental analysis (CHN), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and zeta potential, and were morphologically characterized by scanning electron microscopy (SEM), low-angle X-ray diffraction (XRD) and transmission electron microscopy (TEM) techniques. Results indicate that functionalization process was successfully achieved. Next, functionalized silica nanoparticles were radiolabeled with technetium-99m showing high radiochemical yields and high radiolabeled stability. These findings allow the use of the particles for in vivo applications. Biodistribution and scintigraphic images were carried out in healthy mice in order to determine the fate of the particles. Results from in vivo experiments showed high uptake by liver, as expected due to phagocytosis. However, particles also showed a significant uptake in the lungs, indicated by high lung-to-non-target tissue ratio. In summary, taking into account the great potential of these silica mesoporous structures to carry molecules this platform could be a good strategy for theranostic purposes. - Highlights: • Silica mesoporous nanoparticles were successfully prepared. • Functionalization with DTPA was achieved. • High radiolabeled yields and in vitro stability were reached. • Biodistribution and scintigraphic images were performed.

  16. Generation and customization of biosynthetic excitable tissues for electrophysiological studies and cell-based therapies.

    Science.gov (United States)

    Nguyen, Hung X; Kirkton, Robert D; Bursac, Nenad

    2018-05-01

    We describe a two-stage protocol to generate electrically excitable and actively conducting cell networks with stable and customizable electrophysiological phenotypes. Using this method, we have engineered monoclonally derived excitable tissues as a robust and reproducible platform to investigate how specific ion channels and mutations affect action potential (AP) shape and conduction. In the first stage of the protocol, we combine computational modeling, site-directed mutagenesis, and electrophysiological techniques to derive optimal sets of mammalian and/or prokaryotic ion channels that produce specific AP shape and conduction characteristics. In the second stage of the protocol, selected ion channels are stably expressed in unexcitable human cells by means of viral or nonviral delivery, followed by flow cytometry or antibiotic selection to purify the desired phenotype. This protocol can be used with traditional heterologous expression systems or primary excitable cells, and application of this method to primary fibroblasts may enable an alternative approach to cardiac cell therapy. Compared with existing methods, this protocol generates a well-defined, relatively homogeneous electrophysiological phenotype of excitable cells that facilitates experimental and computational studies of AP conduction and can decrease arrhythmogenic risk upon cell transplantation. Although basic cell culture and molecular biology techniques are sufficient to generate excitable tissues using the described protocol, experience with patch-clamp techniques is required to characterize and optimize derived cell populations.

  17. Nerve and muscle involvement in mitochondrial disorders: an electrophysiological study.

    Science.gov (United States)

    Mancuso, Michelangelo; Piazza, Selina; Volpi, Leda; Orsucci, Daniele; Calsolaro, Valeria; Caldarazzo Ienco, Elena; Carlesi, Cecilia; Rocchi, Anna; Petrozzi, Lucia; Calabrese, Rosanna; Siciliano, Gabriele

    2012-04-01

    Involvement of the peripheral nervous system in mitochondrial disorders (MD) has been previously reported. However, the exact prevalence of peripheral neuropathy and/or myopathy in MD is still unclear. In order to evaluate the prevalence of neuropathy and myopathy in MD, we performed sensory and motor nerve conduction studies (NCS) and concentric needle electromyography (EMG) in 44 unselected MD patients. NCS were abnormal in 36.4% of cases, and were consistent with a sensori-motor axonal multineuropathy (multifocal neuropathy), mainly affecting the lower limbs. EMG evidence of myopathy was present in 54.5% of patients, again mainly affecting the lower limbs. Nerve and muscle involvement was frequently subclinical. Peripheral nerve and muscle involvement is common in MD patients. Our study supports the variability of the clinical expression of MD. Further studies are needed to better understand the molecular basis underlying the phenotypic variability among MD patients.

  18. Electrophysiological studies in the post-viral fatigue syndrome.

    OpenAIRE

    Jamal, G A; Hansen, S

    1985-01-01

    Single fibre electromyography (SFEMG) was studied in 40 patients with the post-viral fatigue syndrome. These patients were also assessed clinically, serologically, virologically and immunologically. About 75% of the patients had definitely abnormal SFEMG results. This was regarded as evidence of abnormality in the peripheral part of the motor unit. The muscle fibre was the likely site of involvement.

  19. The spectrum of Mobius syndrome: an electrophysiological study.

    NARCIS (Netherlands)

    Verzijl, H.T.F.M.; Padberg, G.W.A.M.; Zwarts, M.J.

    2005-01-01

    We studied the nature and extent of facial muscle innervation and the involvement of the motor and sensory long tracts in Mobius syndrome, in order to shed light on the pathophysiological mechanism of the syndrome. Standardized blink reflexes, direct responses of the facial nerves to the orbicularis

  20. Increased dopaminergic activity in socially isolated rats: an electrophysiological study

    DEFF Research Database (Denmark)

    Fabricius, Katrine; Helboe, Lone; Fink-Jensen, Anders

    2010-01-01

    The development of animal models mimicking symptoms associated with schizophrenia has been a critical step in understanding the neurobiological mechanisms underlying the disease. Long-term social isolation from weaning in rodents, a model based on the neurodevelopmental hypothesis of schizophrenia......, has been suggested to mimic some of the deficits seen in schizophrenic patients. We confirm in the present study that socially isolated rats display an increase in both spontaneous and d-amphetamine-induced locomotor activity, as well as deficits in sensorimotor gating as assessed in a pre......, and a change of firing activity towards a more irregular and bursting firing pattern. Taken together, our findings suggest that the behavioral phenotype induced by social isolation may be driven by an overactive dopamine system....

  1. Biodistribution of Boron compounds in an experimental model of liver metastases for Boron Neutron Capture (BNCT) Studies

    International Nuclear Information System (INIS)

    Garabalino, Marcela A.; Monti Hughes, Andrea; Molinari, Ana J.; Heber, Elisa M.; Pozzi, Emiliano C.C.; Itoiz, Maria E.; Trivillin, Veronica A.; Schwint, Amanda E.; Nievas, Susana; Aromando, Romina F.

    2009-01-01

    Boron Neutron Capture Therapy (BNCT) is a binary treatment modality that involves the selective accumulation of 10 B carriers in tumors followed by irradiation with thermal or epithermal neutrons. The high linear energy transfer alpha particles and recoiling 7 Li nuclei emitted during the capture of a thermal neutron by a 10 B nucleus have a short range and a high biological effectiveness. Thus, BNCT would potentially target neoplastic tissue selectively. In previous studies we demonstrated the therapeutic efficacy of different BNCT protocols in an experimental model of oral cancer. More recently we performed experimental studies in normal rat liver that evidenced the feasibility of treating liver metastases employing a novel BNCT protocol proposed by JEC based on ex-situ treatment and partial liver auto-transplant. The aim of the present study was to perform biodistribution studies with different boron compounds and different administration protocols to determine the protocols that would be therapeutically useful in 'in vivo' BNCT studies at the RA-3 Nuclear Reactor in an experimental model of liver metastases in rats. Materials and Methods. A total of 70 BDIX rats (Charles River Lab., MA, USA) were inoculated in the liver with syngeneic colon cancer cells DH/DK12/TRb (ECACC, UK) to induce the development of subcapsular metastatic nodules. 15 days post-inoculation the animals were used for biodistribution studies. A total of 11 protocols were evaluated employing the boron compounds boronophenylalanine (BPA) and GB-10 (Na 2 10 B 1 -0H 10 ), alone or combined employing different doses and administration routes. Tumor, normal tissue and blood samples were processed for boron measurement by ICP-OES. Results. Several protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue, i.e. BPA 15.5 mg 10 B/kg iv + GB-10 50 mg 10 B/kg iv; BPA 46.5 mg 10 B/kg ip; BPA 46.5 mg 10 B/kg ip

  2. Evidence-based medicine evaluation of electrophysiological studies of the anxiety disorders.

    Science.gov (United States)

    Clark, C Richard; Galletly, Cherrie A; Ash, David J; Moores, Kathryn A; Penrose, Rebecca A; McFarlane, Alexander C

    2009-04-01

    We provide a systematic, evidence-based medicine (EBM) review of the field of electrophysiology in the anxiety disorders. Presently, electrophysiological studies of anxiety focus primarily on etiological aspects of brain dysfunction. The review highlights many functional similarities across studies, but also identifies patterns that clearly differentiate disorder classifications. Such measures offer clinical utility as reliable and objective indicators of brain dysfunction in individuals and indicate potential as biomarkers for the improvement of diagnostic specificity and for informing treatment decisions and prognostic assessments. Common to most of the anxiety disorders is basal instability in cortical arousal, as reflected in measures of quantitative electroencephalography (qEEG). Resting electroencephalographic (EEG) measures tend to correlate with symptom sub-patterns and be exacerbated by condition-specific stimulation. Also common to most of the anxiety disorders are condition-specific difficulties with sensory gating and the allocation and deployment of attention. These are clearly evident from evoked potential (EP) and event-related potential (ERP) electrical measures of information processing in obsessive compulsive disorder (OCD), post-traumatic stress disorder (PTSD), panic disorder (PD), generalized anxiety disorder (GAD) and the phobias. Other'ERP measures clearly differentiate the disorders. However, there is considerable variation across studies, with inclusion and exclusion criteria, medication status and control group selection not standardized within condition or across studies. Study numbers generally preclude analysis for confound removal or for the derivation of diagnostic biomarker patterns at this time. The current trend towards development of databases of brain and cognitive function is likely to obviate these difficulties. In particular, electrophysiological measures of function are likely to play a significant role in the development and

  3. Biodistribution study with combined administration of BPA and BSH for BNCT in the hamster cheek pouch oral cancer model

    International Nuclear Information System (INIS)

    Garabalino, M A; Heber, E M; Monti Hughes, A; Pzzi, E C C; Molinari, A J; Niggg, D W; Bauer, W; Trivillin, V A; Schwint, A E

    2012-01-01

    We previously proved the therapeutic potential of the chemically non-selective boron compound decahydrodecaborate (GB-10) as a stand-alone boron carrier for BNCT in the hamster cheek pouch oral cancer model with no toxic effects in normal or precancerous tissue. Although GB-10 is not taken up selectively by oral tumor tissue, selective tumor lethality would result from selective aberrant tumor blood vessel damage. Furthermore, BNCT efficacy was enhanced when GB-10 and boronophenylalanine (BPA) were administered jointly. The fact that sodium mercaptoundecahydro-closo-dodecaborate (BSH) is being investigated clinically as a stand-alone boron agent for BNCT of brain tumors and in combination with BPA for recurrent head and neck malignancies makes it a particularly interesting boron compound to explore. Based on the working hypothesis that BSH would conceivably behave similarly to GB-10 in oral cancer, we previously performed biodistribution studies with BSH alone in the hamster cheek pouch oral cancer model. The aim of the present study was to perform biodistribution studies of BSH + BPA administered jointly in the hamster cheek pouch oral cancer model as a starting point to contribute to the knowledge of (BSH+BPA)-BNCT radiobiology and optimize therapeutic efficacy. The right cheek pouch of Syrian hamsters was subjected to topical administration of a carcinogen twice a week for 12 weeks. Once the exophytic tumors, i.e. squamous cell carcinomas, had developed, the animals were used for biodistribution studies with BSH + BPA. Three administration protocols with different proportions of each of the compounds were assessed: 1. BSH, 50 mg 10 B/kg, iv + BPA, 15.5 mg 10 B/kg, ip; 2. BSH, 34.5 mg 10 B/kg, iv + BPA, 31 mg 10 B/kg, ip; 3. BSH, 20 mg 10 B/kg, iv + BPA, 46.5 mg 10 B/kg, ip. Groups of animals were euthanized 4 h after the administration of BSH and 3 h after the administration of BPA. Samples of blood, tumor, precancerous and normal pouch and other tissues with

  4. Labeling, stability and biodistribution studies of {sup 99m}Tc-cyclized Tyr{sup 3}-octreotate derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Bigott-Hennkens, Heather M. [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Dannoon, Shorouk F.; Noll, Samantha M. [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Ruthengael, Varyanna C. [Research Service, Harry S Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Jurisson, Silvia S., E-mail: JurissonS@missouri.ed [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Lewis, Michael R., E-mail: LewisMic@missouri.ed [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States)

    2011-05-15

    Introduction: To probe the interplay between radiotracer stability and somatostatin receptor affinity, Tyr{sup 3}-octreotate and six variations of its peptide sequence, for which the Re-cyclized products were previously reported, were radiolabeled with {sup 99m}Tc and investigated for their in vitro stability. Methods: Radiolabeling of the peptides was effected by ligand exchange from {sup 99m}Tc-glucoheptonate, and the desired products were purified by radio-RP-HPLC. The in vitro stability in phosphate buffered saline, mouse serum and cysteine solutions at physiological temperature and pH for all seven {sup 99m}Tc-cyclized peptides was determined by radio-RP-HPLC and radio-TLC. Normal CF-1 mouse biodistribution studies were performed for three of the {sup 99m}Tc-cyclized peptides. Results: Based on the fully characterized Re-cyclized peptide analogues, four {sup 99m}Tc-coordination motifs were proposed for the {sup 99m}Tc-cyclized peptides. Technetium-99m-cyclized Tyr{sup 3}-octreotate derivatives with N{sub 2}S{sub 2} metal coordination modes and large metal ring sizes were susceptible to oxidation and loss of {sup 99m}Tc in the form of {sup 99m}TcO{sub 4}{sup -}, as evidenced by their instability in the various solutions under physiological conditions (15-58% intact at 24 h). As anticipated, the addition of a third cysteine to the sequence stabilized the {sup 99m}Tc metal coordination, and peptides with NS{sub 3} coordination modes remained >85% intact out to 24 h. No significant differences were observed in the biodistribution studies performed with three peptides of varying stabilities. Conclusions: Improvements in stability were not sufficient to outweigh the low somatostatin receptor affinity for the peptides in this study. Further improvements in the peptide sequence and/or metal coordination are needed to result in a radiodiagnostic/radiotherapeutic pair for targeting the somatostatin receptor.

  5. Clinical neurological examination vs electrophysiological studies: Reflections from experiences in occupational medicine

    DEFF Research Database (Denmark)

    Jepsen, Jørgen Riis

    2015-01-01

    a diagnosis requires the identification of the responsible pathology and the involved tissues and structures. Consequently, improved diagnostic approaches are needed. This editorial discusses the potentials of using the clinical neurologic examination in patients with upper limb complaints related to work....... It is argued that a simple but systematic physical approach permits the examiner to frequently identify patterns of neurological findings that suggest nerve afflictions and their locations, and that electrophysiological studies are less likely to identify pathology. A diagnostic algorithm for the physical...... assessment is provided to assist the clinician. Failure to include representative neurological items in the physical examination may result in patients being misinterpreted, misdiagnosed and mistreated....

  6. Comparative pharmacokinetics and biodistribution studies of {sup 99m}Tc-annexin V produced by different radiolabeling methods

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Josefina da Silva; Pujatti, Priscilla Brunelli; Couto, Renata Martinussi; Mengatti, Jair; Araujo, Elaine Bortoleti de, E-mail: jssantos@usp.b, E-mail: priscillapujatti@yahoo.com.b, E-mail: renatamartinussicouto@yahoo.com.b, E-mail: jmengatti@ipen.b, E-mail: ebaraujo@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2009-07-01

    The use of radiolabeled annexin A5 (ANXA5) to detect cell death in vivo has increased in the last years. Several {sup 99m}Tc-labeling techniques were reported using different cores, such as [{sup 99m}Tc=O]{sup +3}, [{sup 99m}Tc]HYNIC, [{sup 99m}Tcident toN]{sup +2} and [Tc(CO{sub 3})]{sup +1}. The goal of the present work was to evaluate the influence of {sup 99m}Tc cores in the biological behavior of radiolabeled ANXA5 in Swiss mice using [{sup 99m}Tc=O]{sup +3}, [{sup 99m}Tc]HYNIC cores. Ethylenedicysteine (EC) was applied to obtain [Tc=O]{sup +3} core, N,N,N',N'-tetramethyl(succinimide) uranium tetrafluoroborate (TSTU) was employed to transfer the carboxyl group to their corresponding hydroxysuccinimide ester and HYNIC-ANXA5 was provided by National Cancer Institute-Frederick. ITLC-SG and HPLC analysis were applied to determine non-desirable products and the stability of preparations was evaluated after incubation at room temperature, 4 deg C and in human serum at 37 deg C. In vivo biodistribution and kinetics studies were performed after the intravenous injection of {sup 99m}Tc-HYNIC-ANXA5 and {sup 99m}Tc-EC-ANXA5 and pharmacokinetic parameters were calculated using Biexp software. ANXA5 was radiolabeled at room temperature with high yield (> 95%). The results of biodistribution in mice showed, as expected, higher renal uptake of {sup 99m}Tc-HYNICANXA5 and higher liver uptake of {sup 99m}Tc-EC-ANXA5. The percent injected activity per gram (% IA/g) in liver at 0.5 hours were 6.52 and 1.09 and in kidneys were 1.59 and 32.2 for {sup 99m}Tc-EC-ANXA5 and {sup 99m}Tc-HYNICANXA5, respectively. The results of radioactivity in blood showed that both HYNIC- and EC- radiolabeled ANXA5 presented fast blood clearance. In this study two {sup 99m}Tc-ANXA5 obtained from three different available radiolabeling methods presently were investigated. Each labeling method possesses unique advantages and disadvantages. (author)

  7. Comparative pharmacokinetics and biodistribution studies of 99mTc-annexin V produced by different radiolabeling methods

    International Nuclear Information System (INIS)

    Santos, Josefina da Silva; Pujatti, Priscilla Brunelli; Couto, Renata Martinussi; Mengatti, Jair; Araujo, Elaine Bortoleti de

    2009-01-01

    The use of radiolabeled annexin A5 (ANXA5) to detect cell death in vivo has increased in the last years. Several 99m Tc-labeling techniques were reported using different cores, such as [ 99m Tc=O] +3 , [ 99m Tc]HYNIC, [ 99m Tc≡N] +2 and [Tc(CO 3 )] +1 . The goal of the present work was to evaluate the influence of 99m Tc cores in the biological behavior of radiolabeled ANXA5 in Swiss mice using [ 99m Tc=O] +3 , [ 99m Tc]HYNIC cores. Ethylenedicysteine (EC) was applied to obtain [Tc=O] +3 core, N,N,N',N'-tetramethyl(succinimide) uranium tetrafluoroborate (TSTU) was employed to transfer the carboxyl group to their corresponding hydroxysuccinimide ester and HYNIC-ANXA5 was provided by National Cancer Institute-Frederick. ITLC-SG and HPLC analysis were applied to determine non-desirable products and the stability of preparations was evaluated after incubation at room temperature, 4 deg C and in human serum at 37 deg C. In vivo biodistribution and kinetics studies were performed after the intravenous injection of 99m Tc-HYNIC-ANXA5 and 99m Tc-EC-ANXA5 and pharmacokinetic parameters were calculated using Biexp software. ANXA5 was radiolabeled at room temperature with high yield (> 95%). The results of biodistribution in mice showed, as expected, higher renal uptake of 99m Tc-HYNICANXA5 and higher liver uptake of 99m Tc-EC-ANXA5. The percent injected activity per gram (% IA/g) in liver at 0.5 hours were 6.52 and 1.09 and in kidneys were 1.59 and 32.2 for 99m Tc-EC-ANXA5 and 99m Tc-HYNICANXA5, respectively. The results of radioactivity in blood showed that both HYNIC- and EC- radiolabeled ANXA5 presented fast blood clearance. In this study two 99m Tc-ANXA5 obtained from three different available radiolabeling methods presently were investigated. Each labeling method possesses unique advantages and disadvantages. (author)

  8. Targeting of VX2 Rabbit Liver Tumor by Selective Delivery of 3-Bromopyruvate: A Biodistribution and Survival Study

    Science.gov (United States)

    Vali, Mustafa; Vossen, Josephina A.; Buijs, Manon; Engles, James M.; Liapi, Eleni; Ventura, Veronica Prieto; Khwaja, Afsheen; Acha-Ngwodo, Obele; Shanmugasundaram, Ganapathy; Syed, Labiq; Wahl, Richard L.; Geschwind, Jean-Francois H.

    2009-01-01

    The aim of this study was to determine the biodistribution and tumor targeting ability of 14C-labeled 3-bromopyruvate ([14C]3-BrPA) after i.a. and i.v. delivery in the VX2 rabbit model. In addition, we evaluated the effects of [14C]3-BrPA on tumor and healthy tissue glucose metabolism by determining 18F-deoxyglucose (FDG) uptake. Last, we determined the survival benefit of i.a. administered 3-BrPA. In total, 60 rabbits with VX2 liver tumor received either 1.75 mM [14C]3-BrPA i.a., 1.75 mM [14C]3-BrPA i.v., 20 mM [14C]3-BrPA i.v., or 25 ml of phosphate-buffered saline (PBS). All rabbits (with the exception of the 20 mM i.v. group) received FDG 1 h before sacrifice. Next, we compared survival of animals treated with i.a. administered 1.75 mM [14C]3-BrPA in 25 ml of PBS (n = 22) with controls (n = 10). After i.a. infusion, tumor uptake of [14C]3-BrPA was 1.8 ± 0.2% percentage of injected dose per gram of tissue (%ID/g), whereas other tissues showed minimal uptake. After i.v. infusion (1.75 mM), tumor uptake of [14C]3-BrPA was 0.03 ± 0.01% ID/g. After i.a. administration of [14C]3-BrPA, tumor uptake of FDG was 26 times lower than in controls. After i.v. administration of [14C]3-BrPA, there was no significant difference in tumor FDG uptake. Survival analysis showed that rabbits treated with 1.75 mM 3-BrPA survived longer (55 days) than controls (18.6 days). Intra-arterially delivered 3-BrPA has a favorable biodistribution profile, combining a high tumor uptake resulting in blockage of FDG uptake with no effects on healthy tissue. The local control of the liver tumor by 3-BrPA resulted in a significant survival benefit. PMID:18591216

  9. Electrophysiological and structural remodeling in heart failure modulate arrhythmogenesis. 2D simulation study.

    Directory of Open Access Journals (Sweden)

    Juan F Gomez

    Full Text Available Heart failure is operationally defined as the inability of the heart to maintain blood flow to meet the needs of the body and it is the final common pathway of various cardiac pathologies. Electrophysiological remodeling, intercellular uncoupling and a pro-fibrotic response have been identified as major arrhythmogenic factors in heart failure.In this study we investigate vulnerability to reentry under heart failure conditions by incorporating established electrophysiological and anatomical remodeling using computer simulations.The electrical activity of human transmural ventricular tissue (5 cm × 5 cm was simulated using the human ventricular action potential model Grandi et al. under control and heart failure conditions. The MacCannell et al. model was used to model fibroblast electrical activity, and their electrotonic interactions with myocytes. Selected degrees of diffuse fibrosis and variations in intercellular coupling were considered and the vulnerable window (VW for reentry was evaluated following cross-field stimulation.No reentry was observed in normal conditions or in the presence of HF ionic remodeling. However, defined amount of fibrosis and/or cellular uncoupling were sufficient to elicit reentrant activity. Under conditions where reentry was generated, HF electrophysiological remodeling did not alter the width of the VW. However, intermediate fibrosis and cellular uncoupling significantly widened the VW. In addition, biphasic behavior was observed, as very high fibrotic content or very low tissue conductivity hampered the development of reentry. Detailed phase analysis of reentry dynamics revealed an increase of phase singularities with progressive fibrotic components.Structural remodeling is a key factor in the genesis of vulnerability to reentry. A range of intermediate levels of fibrosis and intercellular uncoupling can combine to favor reentrant activity.

  10. Development of Nanoemulsion Based Gel Loaded with Phytoconstituents for the Treatment of Urinary Tract Infection and in Vivo Biodistribution Studies

    Directory of Open Access Journals (Sweden)

    Atinderpal Kaur

    2017-12-01

    Full Text Available Purpose: A nanoemulsion based gel containing Polyphenon 60 (P60 and cranberry (CRB has been developed to deliver via intravaginal route for the treatment of urinary tract infection. Methods: Polyphenon 60 and cranberry were loaded in a single nanoemulsion gel (NBG by ultra-sonication method and characterized for particle size, rheological properties, in vitro release and growth curve analysis. P60+CRB NBG were radiolabelled using technetium pertechnetate (99mTc to perform in vivo pharmacokinetic studies in animals. Results: The finalized NE had a droplet size of 58±1 nm. In vitro release of 90.92 ± 0.6% in 8 hr for P60 and 99.39 ± 0.5% in 6 hr for CRB was observed in simulated vaginal fluid. Growth curve of E. coli indicated the inhibitory action of nanoemulsion based gel at the fifth hour of inoculation. Gamma scintigraphy studies on female Sprague-Dawley rats showed transport of nanoemulsion based gel from the vaginal cavity into the systemic circulation. Further, biodistribution studies with radiolabelled P60+CRB NBG showed significant higher uptake of radiolabelled actives by kidney (3.20±0.16 and urinary bladder (3.64±0.29, when administered intravaginally. Conclusion: The findings suggested 99mTc-P60+CRB NBG can potentially be transported through vaginal cavity and reach the target organs and showed effective distribution in organs affected in urinary tract infection

  11. Practicality of the cyclotron production of radiolanthanide 142Pr. A potential for therapeutic applications and biodistribution studies

    International Nuclear Information System (INIS)

    Mahdi Sadeghi; Bakht, M.K.; Leila Mokhtari

    2011-01-01

    Radiolanthanide praseodymium-142 (T 1/2 = 19.12 h, E β - = 2.162 MeV (96.3%), E γ = 1575 keV (3.7%)) due to its high β-emission and low specific γ-emission could not only be a therapeutic radionuclide, but also a suitable radionuclide in order for biodistribution studies. Conventionally, 142 Pr produces via 141 Pr(n,γ) 142 Pr reaction by irradiation in a low-fluence reactor and this study evaluates cyclotron reaction production of it. 142 Pr excitation function via nat La(α,n) 142 Pr, 142 Ce(p,n) 142 Pr, and nat Pr(d,p) 142 Pr reactions were calculated by TALYS-1.2 and EMPIRE-2.19beta codes, and with the data taken from the TENDL-2010 database. In addition, we compared them with the reported measurement by experimental data. Requisite thickness of targets was obtained by SRIM-2010 code for each reaction. The 142 Pr production yield was evaluated with attention to excitation function and stopping power. Similar to reactor produced 142 Pr; 141 Pr impurity exists in cyclotron produced 142 Pr while it could not be separated by chemical methods. Therefore, cyclotron and reactor produced 142 Pr will be in carrier added form. (author)

  12. Targeting of liver tumour in rats by selective delivery of holmium-166 loaded microspheres: a biodistribution study

    Energy Technology Data Exchange (ETDEWEB)

    Nijsen, F.; Rook, D.; Zonnenberg, B.; Klerk, J. de; Rijk, P. van; Schip, F. van het [Dept. of Nuclear Medicine, University Medical Center, Utrecht (Netherlands); Brandt, C. [Animal Inst., Utrecht Univ. (Netherlands); Meijer, R. [Dept. of Radiology, Univ. Medical Center, Utrecht (Netherlands); Dullens, H. [Dept. of Pathology, Univ. Medical Center, Utrecht (Netherlands); Hennink, W. [Dept. of Pharmaceutics, Utrecht Univ. (Netherlands)

    2001-06-01

    Intra-arterial administration of beta-emitting particles that become trapped in the vascular bed of a tumour and remain there while delivering high doses, represents a unique approach in the treatment of both primary and metastatic liver tumours. Studies on selective internal radiation therapy of colorectal liver metastases using yttrium-90 glass microspheres have shown encouraging results. This study describes the biodistribution of 40-{mu}m poly lactic acid microspheres loaded with radioactive holmium-166, after intra-arterial administration into the hepatic artery of rats with implanted liver tumours. Radioactivity measurements showed >95% retention of injected activity in the liver and its resident tumour. The average activity detected in other tissues was {<=}0.1%ID/g, with incidental exceptions in the lungs and stomach. Very little {sup 166}Ho activity was detected in kidneys (<0.1%ID/g), thereby indicating the stability of the microspheres in vivo. Tumour targeting was very effective, with a mean tumour to liver ratio of 6.1{+-}2.9 for rats with tumour (n=15) versus 0.7{+-}0.5 for control rats (n=6; P<0.001). These ratios were not significantly affected by the use of adrenaline. Histological analysis showed that five times as many large (>10) and medium-sized (4-9) clusters of microspheres were present within tumour and peritumoural tissue, compared with normal liver. Single microspheres were equally dispersed throughout the tumour, as well as normal liver parenchyma. (orig.)

  13. Review Article. Electrophysiological Methods for Study of Changes in Visual Analyzer in Patients with Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Elena Mermeklieva

    2017-03-01

    Full Text Available The electrophysiological (EF methods are objective methods for studying the visual analyzer function. These include electroretinography (ERG, electrooculography (EOG and visual evoked potentials (VEPs. ERG and EOG are used for diagnosis and monitoring of a number of diseases of the retina. VEPs depend on the functional integrity of the entire optical path from the retina through the optic nerve, optic tract, the optical radiation to the visual cortex. The electrophysiological methods are widely used in studying the function of the visual analyzer in the ophthalmic and neurological practice, for objectively measuring the visual acuity and the visual field in non-cooperative patients, small children and in simulation. Diabetes mellitus (DM is a group of metabolic diseases characterized by hyperglycemia. One of the late complications of DM is diabetic retinopathy (DR. It is one of the most serious complications of diabetes, often leading to blindness. Nowadays, DR includes retinal neurodegeneration and microvascular complications. By EF studies can evaluate the function of the retina in diabetic patients in an objective manner using ERG, that reflects the EF activity of the neurons in the retina and VEPs, which indicate the electrical conductivity across the optic tract to the visual cortex.

  14. Preclinical good laboratory practice-compliant safety study to evaluate biodistribution and tumorigenicity of a cartilage advanced therapy medicinal product (ATMP).

    Science.gov (United States)

    Zscharnack, Matthias; Krause, Christoph; Aust, Gabriela; Thümmler, Christian; Peinemann, Frank; Keller, Thomas; Smink, Jeske J; Holland, Heidrun; Somerson, Jeremy S; Knauer, Jens; Schulz, Ronny M; Lehmann, Jörg

    2015-05-20

    The clinical development of advanced therapy medicinal products (ATMPs), a new class of drugs, requires initial safety studies that deviate from standard non-clinical safety protocols. The study provides a strategy to address the safety aspects of biodistribution and tumorigenicity of ATMPs under good laboratory practice (GLP) conditions avoiding cell product manipulation. Moreover, the strategy was applied on a human ATMP for cartilage repair. The testing strategy addresses biodistribution and tumorigenicity using a multi-step analysis without any cell manipulation to exclude changes of test item characteristics. As a safeguard measurement for meeting regulatory expectations, the project design and goals were discussed continuously with the regulatory authority using a staggered scientific advice concept. Subsequently, the strategy was applied to co.don chondrosphere® (huChon spheroid), a tissue-engineered matrix-free ATMP of human normal chondrocytes. In both the biodistribution and tumorigenicity studies, huChon spheroids were implanted subcutaneously into 40 immunodeficient mice. Biodistribution was studied 1 month after implantation. A skin disc containing the huChon spheroid, two surrounding skin rings and selected organs were analyzed by validated, gender-specific, highly-sensitive triplex qPCR and by immunohistochemistry (IHC). No human DNA was detected in distant skin rings and analyzed organs. IHC revealed no direct or indirect indications of cell migration. Tumorigenicity was assessed 6 months after huChon spheroid implantation by palpation, macroscopic inspection, histology and IHC. No mice from the huChon spheroid group developed a tumor at the implantation site. In two mice, benign tumors were detected that were negative for HLA-ABC, suggesting that they were of spontaneous murine origin. In summary, the presented strategy using a multi-step analysis was confirmed to be suitable for safety studies of ATMPs.

  15. Radiolabeling of substance P with Lutetium-177 and biodistribution study in AR42J pancreatic tumor xenografted Nude mice

    International Nuclear Information System (INIS)

    Araujo, Bortoleti de; Pujatti, Priscilla Brunelli; Barrio, Ofelia; Caldeira, Jose S.; Mengatti, Jair; Suzuki, Miriam F.

    2008-01-01

    Pancreatic tumor (PT) is a neuroendocrine neoplasm that usually origin metastases in the respiratory and gastrointestinal tract. In recent years, new developments in targeted therapies have emerged and the presence of peptide receptors at the cell membrane of PT constitutes the basis of the clinical use of specific radiolabeled ligands. Substance P, an 11-amino acid peptide which has an important role in modulating pain transmission trough neurokinin 1 and 2 receptors (NKr), may play a role in the pathogenesis of PT, because approximately 10% of these tumors over express NKr. The aim of the present work was to produce a pure and stable SP analog (DOTA-SP) radiolabeled with Lutetium-177 ( 177 Lu), and to evaluate its in vivo target to AR42J pancreatic tumor cells in Nude mice in other to verify if SP can be used in this pancreatic tumor detection and treatment. 177 Lu (half-life 6.7 days) has both β and γ-emissions suitable for radiotherapy and imaging respectively. Substance P was successfully labeled with high yield (>99%) at optimized conditions and kept stable for more than 72 hours at 4 deg C and 24 hours in human plasma. Biodistribution studies showed that SP excretion was mainly performed by renal pathway. In addition, 177 Lu-DOTA-SP showed higher uptake by tumor than normal pancreas, indicating the presence of NK receptors in AR42J pancreatic tumor. (author)

  16. Biodistribution study of the anesthetic sodium phenobarbital labelled with technetium-99 in swiss mice infected with Schistosoma mansoni Sambon, 1907

    Energy Technology Data Exchange (ETDEWEB)

    Simoes, Susana Balmant Emerique; Machado Silva, Jose Roberto [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Faculdade de Ciencias Medicas. Dept. de Patologia e Laboratorios; Gutfilen, Bianca; Oliveira, Marcia Betania; Bernardo Filho, Mario [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Biologia. Dept. de Biofisica e Biometria; Presgrave, Otavio Augusto Franca [Fundacao Inst. Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ (Brazil). Inst. Nacional de de Controle de Qaulidade em Saude. Dept. de Farmacologia e Toxicologia

    1997-09-01

    Technetium-99 m ({sup 99m} Tc) is a radionuclide that has negligible environmental impact, is easily available, inexpensive and can be used as a radioactive tracer in biological experiences. In order to know the mode of action of sodium phenobarbital in moving adult Schistosoma mansoni worms from mesenteric veins to the liver, we labelled sodium phenobarbital (PBBT) with {sup 99m} Tc and a biodistribution study in infected and non-infected Swiss mice was performed. The PBBT was incubated with stannous chloride used as reducing agent and with {sup 99m} Tc, as sodium pertechnetate. The radioactivity labelling(%) was determined by paper ascending chromatography performed with acetone (solvent). The{sup 99m} Tc-PBBT was administered by intraperitoneal route to Swiss mice infected eight weeks before. The animals were perfused after different periods of time (0,1,2,3,4 hr) when blood, spleen, liver, portal vein, mesenteric veins, stomach, kidneys and adult worms were isolated. The radioactivity present in these samples was counted in a well counter and the percentage was determined. THe radioactivity was mainly taken up by the blood, kidney, liver and spleen. No radioactivity was found on the adult worms. We concluded that the worm shift was due to an action on the host of the sodium phenobarbital. (author) 24 refs., 3 tabs.

  17. Biodistribution study of the anesthetic sodium phenobarbital labelled with technetium-99 in swiss mice infected with Schistosoma mansoni Sambon, 1907

    International Nuclear Information System (INIS)

    Simoes, Susana Balmant Emerique; Machado Silva, Jose Roberto; Gutfilen, Bianca; Oliveira, Marcia Betania; Bernardo Filho, Mario; Presgrave, Otavio Augusto Franca

    1997-01-01

    Technetium-99 m ( 99m Tc) is a radionuclide that has negligible environmental impact, is easily available, inexpensive and can be used as a radioactive tracer in biological experiences. In order to know the mode of action of sodium phenobarbital in moving adult Schistosoma mansoni worms from mesenteric veins to the liver, we labelled sodium phenobarbital (PBBT) with 99m Tc and a biodistribution study in infected and non-infected Swiss mice was performed. The PBBT was incubated with stannous chloride used as reducing agent and with 99m Tc, as sodium pertechnetate. The radioactivity labelling(%) was determined by paper ascending chromatography performed with acetone (solvent). The 99m Tc-PBBT was administered by intraperitoneal route to Swiss mice infected eight weeks before. The animals were perfused after different periods of time (0,1,2,3,4 hr) when blood, spleen, liver, portal vein, mesenteric veins, stomach, kidneys and adult worms were isolated. The radioactivity present in these samples was counted in a well counter and the percentage was determined. THe radioactivity was mainly taken up by the blood, kidney, liver and spleen. No radioactivity was found on the adult worms. We concluded that the worm shift was due to an action on the host of the sodium phenobarbital. (author)

  18. Evaluation of labelling conditions, quality control and biodistribution study of 99mTc-5-aminolevulinic acid (5-ALA). A potential liver imaging agent

    International Nuclear Information System (INIS)

    Kalim Ullah Khan; Mohammad Rafi; Samina Roohi; Rizwana Zahoor; Zafar Iqbal; Mushtaq Ahmad

    2014-01-01

    Labelling of 5-aminolevulinic acid (5-ALA) with 99m Tc was achieved by using SnCl 2 ·2H 2 O as reducing agent. Radiochemical purity and labelling efficiency was determined by instant thin layer chromatography/paper chromatography. Efficiency of labelling was dependent on many parameters such as amount of ligand, reducing agent, pH, and time of incubation. 99m Tc labelled 5-ALA remained stable for 24 h in human serum. Tissue biodistribution of 99m Tc-5-ALA was evaluated in Sprague-Dawley rats. Biodistribution study (% ID/g) in rats revealed that 99m Tc-5-ALA was accumulated significantly in liver, spleen, stomach and intestine after half hour, 4 and 24 h. Significant activity was noted in bladder and urine at 4 h. High liver uptake of 99m Tc-5-ALA makes it a promising liver imaging agent. (author)

  19. 4 cases of 'ataxic hemiparesis'. A comparative study of computed tomography and electrophysiological findings

    Energy Technology Data Exchange (ETDEWEB)

    Eguchi, Kiyoshi; Kamei, Hidekazu; Kitamura, Eiko; Komatsuzaki, Satoshi; Yamane, Kiyomi; Takemiya, Toshiko; Kobayashi, Itsuro; Maruyama, Shoichi

    1984-10-01

    Ataxic hemiparesis is described as a syndrome in which pyramidal and cerebellar signs occur ipsilaterally. Fisher who suggested the designation ''ataxic hemiparesis'' for this syndrome confirmed by pathological study that causative lesion was in the basis pontis at the level of the junction of the upper one third and lower two thirds on the opposite side of the neurological deficit and he also reported that CT might fail to show the lesion. We observed 4 patients with ataxic hemiparesis and examined them in auditory brainstem response (ABR), somatosensory evoked potential (SEP), and blink reflex as electrophysiological study. Their CT and electrophysiological findings were compared with each others to define the responsible lesion more clearly. Essentially, these abnormal electrophysiological findings were recognized only in the case of pontine hemorrhage, and these findings recovered to normal as clinical and CT findings were improved. In the other cases, the electrophysiological findings were not prominent and CT revealed the lesions in deep frontal region, internal capsule and cerebellar hemispheres respectively. These results might show that many cases of extra-pontine lesions could develop the syndrome of ataxic hemiparesis. However, the relation between responsible lesions for ataxic hemiparesis and electrophysiological findings are still uncertain. Further evidences including clinicopathological studies will be required to clarify this relation and to get the more accurate anatomical interpretation of ataxic hemiparesis from lesions besides the pontine region. (author).

  20. Labeling of the peptide DOTA-tyr3-octreotate with radioiodine and biodistribution and AR42J neuroendocrine tumor affinity study in mice

    International Nuclear Information System (INIS)

    Nagamati, Lucio Takeshi

    2006-01-01

    Neuroendocrine tumors are rare and affect mainly the gastrointestinal tract but other systems are also affected like the skin, lungs and the nervous system. They are rich in type 2 somatostatin (SM) receptors (SSTR2) and may secrete hormones in excess. Synthetic SM derivative peptides are of great utility because presented bigger half life when compared to SM and can be used to clinical improvement of these patients due to its tumoral inhibitory action. The labeling of these peptides with radioisotopes allowed the acquisition of images with favourable cost-efficiency relationship and use in therapy. The peptide, DOTATyr3- octreotate (DOTATATE), has much more affinity for the SSTR2 receptor than the peptide commercially used nowadays, is easily radioiodinated and has a favourable biodistribution for diagnosis and treatment due to the presence of the chelator DOTA. We have studied the influence of various factors on the radiochemical purity of the labeled compound as labeling stability, absorbed dose estimation and biodistribution in normal and AR42J cell tumor-bearing Swiss and Nude mice. We observed easy and stable peptide radioiodination at peptide/radioiodine ( 131 I) ratio of 2.73 that produced a radiochemical species with retention time of 22.7 minutes at high performance liquid chromatography and presented a favourable biodistribution and dosimetry for imaging and therapy of patients with neuroendocrine tumors, just the opposite result observed the radioiodinated compounds without a chelator as described in the literature. Other molar peptide/radioiodine ratios did not showed good results, with various radiochemical species and unfavourable biodistribution. A possible dosimetric study in patients with neuroendocrine tumors may be carried out in the near future. (author)

  1. A Comparison of Three Transarterial Lipiodol-Based Formulations for Hepatocellular Carcinoma: In Vivo Biodistribution Study in Humans

    International Nuclear Information System (INIS)

    Yu, Simon Chun Ho; Leung, Thomas Wai Tong; Lau, Wan Yee; Lee, Nelson; Hui, Edwin Pun; Yeo, Winnie; Lai, Paul Bo San; Mok, Tony Shu Kam

    2008-01-01

    This study aimed to evaluate and compare the biodistribution properties of three transarterial Lipiodol-based therapeutic regimens in human hepatocellular carcinoma (HCC). In this prospective study with 13 patients randomly allocated to one of three study groups, each of the patients received transcatheter intra-arterial administration into a solitary HCC with one of three different Lipiodol-based formulations: Lipiodol-ethanol mixture (LEM; Group A), Lipiodol alone (Group B), and Lipiodol and gelatin pledgets (Group C). With the use of radioactive iodine-131-labeled Lipiodol, each group was assessed for (1) pattern of Lipiodol accumulation in the lungs within the first 2 weeks as evaluated by single-photon emission computed tomography and (2) decomposition of Lipiodol formulation within the first 2 weeks as evaluated by radioactivity detected in peripheral blood and urine. The degree of Lipiodol retention in the tumor within the first 4 weeks was evaluated with CT. No statistically significant difference in Lipiodol accumulation in the lungs was detected among the three groups. However, the peak accumulation in the lungs was delayed 3 days for Group A compared to Groups B and C. The degree of Lipiodol retention within the tumor in Group A was significantly greater than that in Groups B and C on day 14 (p = 0.014) and day 28 (p = 0.013). This study showed that LEM is associated with a greater embolic effect in intrahepatic HCC at 4 weeks, and a comparable degree of lung shunting and decomposition rates, compared with ethanol-free Lipiodol formulations

  2. Effects of intraoperative irradiation and intraoperative hyperthermia on canine sciatic nerve: neurologic and electrophysiologic study

    International Nuclear Information System (INIS)

    Vujaskovic, Zeljko; Gillette, Sharon M.; Powers, Barbara E.; Stukel, Therese A.; LaRue, Susan M.; Gillette, Edward L.; Borak, Thomas B.; Scott, Robert J.; Weiss, Julia; Colacchio, Thomas A.

    1996-01-01

    Purpose: Late radiation injury to peripheral nerve may be the limiting factor in the clinical application of intraoperative radiation therapy (IORT). The combination of IORT with intraoperative hyperthermia (IOHT) raises specific concerns regarding the effects on certain normal tissues such as peripheral nerve, which might be included in the treatment field. The objective of this study was to compare the effect of IORT alone to the effect of IORT combined with IOHT on peripheral nerve in normal beagle dogs. Methods and Materials: Young adult beagle dogs were randomized into five groups of three to five dogs each to receive IORT doses of 16, 20, 24, 28, or 32 Gy to 5 cm of surgically exposed right sciatic nerve using 6 MeV electrons and six groups of four to five dogs each received IORT doses of 0, 12, 16, 20, 24, or 28 Gy simultaneously with 44 deg. C of IOHT for 60 min. IOHT was performed using a water circulating hyperthermia device with a multichannel thermometry system on the surgically exposed sciatic nerve. Neurologic and electrophysiologic examinations were done before and monthly after treatment for 24 months. Electrophysiologic studies included electromyographic (EMG) examinations of motor function, as well as motor nerve conduction velocities studies. Results: Two years after treatment, the effective dose for 50% complication (ED 50 ) for limb paresis in dogs exposed to IORT only was 22 Gy. The ED 50 for paresis in dogs exposed to IORT combined with IOHT was 15 Gy. The thermal enhancement ratio (TER) was 1.5. Electrophysiologic studies showed more prominent changes such as EMG abnormalities, decrease in conduction velocity and amplitude of the action potential, and complete conduction block in dogs that received the combination of IORT and IOHT. The latency to development of peripheral neuropathies was shorter for dogs exposed to the combined treatment. Conclusion: The probability of developing peripheral neuropathies in a large animal model was higher

  3. Comparative study of two different Bombesin derivates labeled with {sup 111}In and biodistribution in normal mice

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Ricardo S.; Alcarde, Lais F.; Correa, Beatriz L.; Massicano, Adriana V.F.; Couto, Renata M.; Mengatti, Jair; Araujo, Elaine B. de, E-mail: ricardooliveira@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Nuclear medicine is a medical speciality that uses radioactive compounds (radiopharmaceuticals), consisting of a substrate and a radioactive isotope, for diagnostic. Among the peptides of interest for Nuclear Medicine, bombesin (BBN), a 14 amino acid neuropeptide analog of human gastrin-releasing peptide, is one of the highlights. This is a comparative study aiming to establish the best condition to radiolabel two BBN derivatives, (DTPA-Phe-Gly{sub 5}-BBN{sub (6-14)}) and (DTPA-Phe-Gly{sub 2}-BBN{sub (6-14})) with 111-indium. Specific objectives of this study were evaluate a good condition of radiolabelling in search excellent specific activity the bombesin derivatives and determinate the biodistribution in health mice model. Ten micrograms (10μg) of the derivative DTPA-Phe-Gly2-BBN (6-14) was labeled with 18.5 MBq (0.5 mCi) of {sup 111}InCl{sub 3} at 25°C for different times (5, 15 and 30 minutes). The best condition was applied to peptide mass variation (10, 5, 2.5, 1, 0.5, 0.25 and 0.1 μg), keeping all other parameters fixed. Finally, the influence of {sup 111}InCl{sub 3} activity in the radiolabeling process (18.5, 37, 55.5, 74, 185 MBq) was evaluated. The best conditions were repeated for the second derivate, DTPA-Phe-Gly{sub 5}-BBN{sub (6-14}). The radiochemical purity was assessed by thin layer chromatography (TLC), using 0.2 M EDTA pH 5 as solvent, and high performance liquid chromatography (HPLC) with a C18 column with linear gradient 10% A to 90% A (v/v) (A: 0,1% of TFA in CH3CN; B: 0,1% of TFA in H2O) at a flow rate of 1 mL/minute for 15 minutes. Considering the reaction time, the higher radiochemical purity was obtained when 10μg of the peptide was labeled with 18.5 MBq (0.5 mCi) of {sup 111}In for 15 minutes at 25°C (97.33 ± 0.50%, n=3). In the mass variation study, the best results of radiochemical purity were obtained when 10 μg of the peptide was employed (97.69 ± 0.4%, n = 4). Finally, the maximum specific activity of the radiolabelled

  4. Fluorescent nanoparticles present in Coca-Cola and Pepsi-Cola: physiochemical properties, cytotoxicity, biodistribution and digestion studies.

    Science.gov (United States)

    Li, Shen; Jiang, Chengkun; Wang, Haitao; Cong, Shuang; Tan, Mingqian

    2018-02-01

    Foodborne nanoparticles (NPs) have drawn great attention due to human health concerns. This study reports the detection of the presence of fluorescent NPs, about 5 nm, in two of the most popular beverages, Coca-Cola (Coke) and Pepsi-Cola (Pepsi). The NPs contain H, C and O, three elements with a tunable emission and with a quantum yield of 3.3 and 4.3% for Coke and Pepsi, respectively. The presence of sp 3 -hybridized carbon atoms of alcohols and ethers bonds was confirmed by NMR analysis. The NPs can be taken up by living cells and accumulate within cell membrane and cytoplasm. Evaluation of the acute toxicity of the NPs revealed that the BALB/c mice appeared healthy after administration of a single dose of 2 g kg -1 body weight. Analysis of glutamate pyruvate transaminase (GPT), glutamic oxaloacetic transaminase (GOT), urea and creatinine showed that there were statistically, but not biologically, significant differences in some of these biochemical parameters between the test and control groups. No obvious organ damage or apparent histopathological abnormality was observed in the tested mice. The biodistribution study in major organs indicated that the NPs were easily accumulated in the digestive tract, and they were able to cross the blood-brain barrier and dispersed in the brain. In vitro digestion of the NPs showed a significant fluorescence quenching of the NPs. This work represents the first report of foodborne fluorescent NPs present in Coke and Pepsi, and provides valuable insights into physicochemical properties of these NPs and their toxicity characteristics both in vitro and in vivo.

  5. Preclinical Study of 68Ga-DOTATOC: Biodistribution Assessment in Syrian Rats and Evaluation of Absorbed Dose in Human Organs.

    Science.gov (United States)

    Naderi, Mojdeh; Zolghadri, Samaneh; Yousefnia, Hassan; Ramazani, Ali; Jalilian, Amir Reza

    2016-01-01

    Gallium-68 DOTA-DPhe 1 -Tyr 3 -Octreotide ( 68 Ga-DOTATOC) has been applied by several European centers for the treatment of a variety of human malignancies. Nevertheless, definitive dosimetric data are yet unavailable. According to the Society of Nuclear Medicine and Molecular Imaging, researchers are investigating the safety and efficacy of this radiotracer to meet Food and Drug Administration requirements. The aim of this study was to introduce the optimized procedure for 68 Ga-DOTATOC preparation, using a novel germanium-68 ( 68 Ge)/ 68 Ga generator in Iran and evaluate the absorbed doses in numerous organs with high accuracy. The optimized conditions for preparing the radiolabeled complex were determined via several experiments by changing the ligand concentration, pH, temperature and incubation time. Radiochemical purity of the complex was assessed, using high-performance liquid chromatography and instant thin-layer chromatography. The absorbed dose of human organs was evaluated, based on biodistribution studies on Syrian rats via Radiation Absorbed Dose Assessment Resource Method. 68 Ga-DOTATOC was prepared with radiochemical purity of >98% and specific activity of 39.6 MBq/nmol. The complex demonstrated great stability at room temperature and in human serum at 37°C at least two hours after preparation. Significant uptake was observed in somatostatin receptor-positive tissues such as pancreatic and adrenal tissues (12.83 %ID/g and 0.91 %ID/g, respectively). Dose estimations in human organs showed that the pancreas, kidneys and adrenal glands received the maximum absorbed doses (0.105, 0.074 and 0.010 mGy/MBq, respectively). Also, the effective absorbed dose was estimated at 0.026 mSv/MBq for 68 Ga-DOTATOC. The obtained results showed that 68 Ga-DOTATOC can be considered as an effective agent for clinical PET imaging in Iran.

  6. The Use of Brain Electrophysiology Techniques To Study Language: A Basic Guide for the Beginning Consumer of Electrophysiology Information.

    Science.gov (United States)

    Molfese, Dennis L.; Molfese, Victoria J.; Kelly, Spencer

    2001-01-01

    This article provides an introduction to the use of event-related potential (ERP) approaches to study language processes. First, a brief history of the emergence of this technology is presented, followed by definitions, a theoretical overview, and a practical guide to conducting ERP studies. Examples of language studies that use this technique are…

  7. Is isoproterenol really required during electrophysiological study in patients with Wolff-Parkinson-White syndrome?

    Science.gov (United States)

    Pauriah, Maheshwar; Cismaru, Gabriel; Sellal, Jean-Marc; De Chillou, Christian; Brembilla-Perrot, Béatrice

    2013-01-01

    We have studied the results of electrophysiological study (EPS) in patients with Wolff-Parkinson-White syndrome (WPW) and spontaneous adverse clinical presentation and determined whether isoproterenol added incremental value. EPS was performed in 63 patients with WPW and adverse clinical presentation at baseline. EPS was repeated after infusion of isoproterenol in 37 patients, including 25 without criteria for a malignant form at baseline. Atrioventricular orthodromic tachycardia was induced 44%, antidromic tachycardia in 11%, atrial fibrillation (AF) in 68% at baseline. At baseline EPS, criteria for a malignant form (AF induction and shortest CL <250 ms) were noted in 60%; tachycardia was not inducible in 16%. All the patients met the criteria for a malignant form after isoproterenol. EPS at baseline missed 16% of patients at risk of life-threatening arrhythmias who had no inducible tachyarrhythmia and 40% without classical criteria for malignant form. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Ion Channel ElectroPhysiology Ontology (ICEPO) - a case study of text mining assisted ontology development.

    Science.gov (United States)

    Elayavilli, Ravikumar Komandur; Liu, Hongfang

    2016-01-01

    Computational modeling of biological cascades is of great interest to quantitative biologists. Biomedical text has been a rich source for quantitative information. Gathering quantitative parameters and values from biomedical text is one significant challenge in the early steps of computational modeling as it involves huge manual effort. While automatically extracting such quantitative information from bio-medical text may offer some relief, lack of ontological representation for a subdomain serves as impedance in normalizing textual extractions to a standard representation. This may render textual extractions less meaningful to the domain experts. In this work, we propose a rule-based approach to automatically extract relations involving quantitative data from biomedical text describing ion channel electrophysiology. We further translated the quantitative assertions extracted through text mining to a formal representation that may help in constructing ontology for ion channel events using a rule based approach. We have developed Ion Channel ElectroPhysiology Ontology (ICEPO) by integrating the information represented in closely related ontologies such as, Cell Physiology Ontology (CPO), and Cardiac Electro Physiology Ontology (CPEO) and the knowledge provided by domain experts. The rule-based system achieved an overall F-measure of 68.93% in extracting the quantitative data assertions system on an independently annotated blind data set. We further made an initial attempt in formalizing the quantitative data assertions extracted from the biomedical text into a formal representation that offers potential to facilitate the integration of text mining into ontological workflow, a novel aspect of this study. This work is a case study where we created a platform that provides formal interaction between ontology development and text mining. We have achieved partial success in extracting quantitative assertions from the biomedical text and formalizing them in ontological

  9. Language effects in second-language learners: A longitudinal electrophysiological study of spanish classroom learning.

    Science.gov (United States)

    Soskey, Laura; Holcomb, Phillip J; Midgley, Katherine J

    2016-09-01

    How do the neural mechanisms involved in word recognition evolve over the course of word learning in adult learners of a new second language? The current study sought to closely track language effects, which are differences in electrophysiological indices of word processing between one's native and second languages, in beginning university learners over the course of a single semester of learning. Monolingual L1 English-speakers enrolled in introductory Spanish were first trained on a list of 228 Spanish words chosen from the vocabulary to be learned in class. Behavioral data from the training session and the following experimental sessions spaced over the course of the semester showed expected learning effects. In the three laboratory sessions participants read words in three lists (English, Spanish and mixed) while performing a go/no-go lexical decision task in which event-related potentials (ERPs) were recorded. As observed in previous studies there were ERP language effects with larger N400s to native than second language words. Importantly, this difference declined over the course of L2 learning with N400 amplitude increasing for new second language words. These results suggest that even over a single semester of learning that new second language words are rapidly incorporated into the word recognition system and begin to take on lexical and semantic properties similar to native language words. Moreover, the results suggest that electrophysiological measures can be used as sensitive measures for tracking the acquisition of new linguistic knowledge. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Behavioral and electrophysiological studies of radiation detection in a freshwater crustacean

    International Nuclear Information System (INIS)

    Rodriguez, A.; Kimeldorf, D.J.

    1976-01-01

    Behavioral and electrophysiological studies were done on the crayfish (Pacifastacus trowbridgii Stimpson) to determine its ability to detect exposure to 300 kVp x rays. Behavioral arousal responses were observed at exposure rates of 10 to 30 R/sec. Wholebody and partial-body exposures of eye-stalkless (blinded) animals also induced similar responses and indicated a radiation-sensitive receptor in the abdomen. Prolonged exposure under free choice of residence conditions induced an avoidance of the x-ray field. X-ray exposure of the dark-adapted compound eye evoked an electroretinogram (ERG) that was similar to the light-evoked ERG. The ERG amplitude was directly proportional to the total exposure with exposures less than 300 msec duration and related to the logarithm of the exposure rate with exposures greater than 300 msec. X-ray exposure of receptor sites on the medial branch of the antennule and the cheliped of the first walking-leg did not yield any significant chemoreceptor responses as judged by electrophysiological tests. X-irradiation of the sixth abdominal ganglion in both isolated and in vivo preparations elicited significant increases in neural impulse activity. The latency varied inversely with exposure rate. Spike potentials evoked by x rays were similar to those evoked by light; however, a supplemental increase in spikes of lower amplitude occurred that did not occur during light stimulation. It appears likely that the behavioral response in the crayfish, subjected to abdomen-only exposure, may be instigated by x-ray excitation of the sixth ganglion

  11. The biodistribution study of 99mTc labelled anti-CEA monoclonal antibody in tumor bearing nude mice

    International Nuclear Information System (INIS)

    Lou Zongxin

    1992-01-01

    The author report the optimal condition of 99m Tc labelling with anti-CEA monoclonal antibody using chelating of 99m Tc with dimethylformamide. The labelling rate of this method is 60%-80%, the radiochemical purity of labelling antibody over 90% and maintain its better immuno activity. The biodistribution of the tumor bearing nude mice demonstrates that as compared with the control group, 24 hours after the intraperitoneal injection the injected labelled antibody has its specific concentration in tumor tissue

  12. Biodistribution of [11C] methylaminoisobutyric acid, a tracer for PET studies on system A amino acid transport in vivo

    International Nuclear Information System (INIS)

    Sutinen, E.; Jyrkkioe, S.; Groenroos, T.; Haaparanta, M.; Lehikoinen, P.; Naagren, K.

    2001-01-01

    [N-methyl- 11 C]α-Methylaminoisobutyric acid ( 11 C-MeAIB) is a potentially useful tracer for positron emission tomography (PET) studies on hormonally regulated system A amino acid transport. 11 C-MeAIB is a metabolically stable amino acid analogue specific for system A amino acid transport. We evaluated the biodistribution of 11 C-MeAIB in rats and humans to estimate the usefulness of the tracer for in vivo human PET studies, for example, on regulation of system A amino acid transport and on tumour imaging. Healthy Sprague-Dawley rats (n=14) were killed 5, 20, 40 or 60 min after the injection of 11 C-MeAIB, and the tissue samples were weighed and counted for 11 C radioactivity. Ten lymphoma patients with relatively limited tumour burden underwent whole-body (WB) PET imaging with 11 C-MeAIB. In addition, three other patients had dynamic PET scanning of the head and neck area, and the tracer uptake was quantitated by calculating the kinetic influx constants (K i values) for the tracer. In animal studies, the highest activity was detected in the kidney, pancreas, adrenal gland and intestines. In humans, the highest activity was found in the salivary glands, and after that in the kidney and pancreas, similar to the results in animal studies. Rapid uptake was also detected in the skeletal muscle. In the graphical analysis, linear plots were obtained, and the mean fractional tracer uptake values (K i ) of the parotid glands (n=3) and cervical muscles (n=3) were 0.039±0.008 min -1 and 0.013±0.006 min -1 , respectively. The K i value of the tumour (n=1) was 0.064 min -1 . Higher uptake of 11 C-MeAIB into the tumour tissue was encountered. These results encourage further 11 C-MeAIB PET studies in humans on the physiology and pathology of system A amino acid transport and on tumour detection. (orig.)

  13. Radiosynthesis of 123I-labeled hesperetin for biodistribution study of orally administered hesperetin

    International Nuclear Information System (INIS)

    Jongho Jeon; So-Young Ma; Dae Seong Choi; Beom-Su Jang; Jung Ae Kang; You Ree Nam; Seonhye Yoon; Sang Hyun Park; Korea University of Science and Technology, Daejeon

    2015-01-01

    The purpose of this study is to synthesize 123 I-labeled hesperetin and to investigate its in vivo behavior. The optimized labeling condition provided two isomers of 123 I-labeled hesperetin with high radiochemical yields and radiochemical purities. Both 123 I-labeled products were orally administered to normal ICR mice, and the initial result showed that most of 123 I activity was detected in the stomach and the intestines. A part of 123 I-labeled hesperetin was absorbed from the small intestine to bloodstream and then it was distributed in normal organs. The results in the present study provided an efficient radiolabeling method of flavonoid and quantitative organ distribution of orally administered hesperetin. (author)

  14. Preclinical safety, pharmacokinetics, pharmacodynamics, and biodistribution studies with Ad35K++ protein: a novel rituximab cotherapeutic

    Directory of Open Access Journals (Sweden)

    Maximilian Richter

    2016-01-01

    Full Text Available Rituximab is a mouse/human chimeric monoclonal antibody targeted toward CD20. It is efficient as first-line therapy of CD20-positive B-cell malignancies. However, a large fraction of treated patients relapse with rituximab-resistant disease. So far, only modest progress has been made in treatment options for rituximab refractory patients. One of the mechanisms for rituximab resistance involves the upregulation of CD46, which is a key cell surface protein that blocks the activation of complement. We have recently developed a technology that depletes CD46 from the cell surface and thereby sensitizes tumor cells to complement-dependent cytotoxicity. This technology is based on a small recombinant protein, Ad35K++ that binds with high affinity to CD46. In preliminary studies using a 6 × histidinyl tagged protein, we had demonstrated that intravenous Ad35K++ injection in combination with rituximab was safe and increased rituximab-mediated killing of CD20-positive target cells in mice and nonhuman primates (NHPs. The presence of the tag, while allowing for easy purification by Ni-NTA chromatography, has the potential to increase the immunogenicity of the recombinant protein. For clinical application, we therefore developed an Ad35K++ protein without His-tag. In the present study, we performed preclinical studies in two animal species (mice and NHPs with this protein demonstrating its safety and efficacy. These studies estimated the Ad35K++ dose range and treatment regimen to be used in patients. Furthermore, we showed that intravenous Ad35K++ injection triggers the shedding of the CD46 extracellular domain in xenograft mouse tumor models and in macaques. Shed serum CD46 can be measured in the serum and can potentially be used as a pharmacodynamic marker for monitoring Ad35K++ activity in patient undergoing treatment with this agent. These studies create the basis for an investigational new drug application for the use of Ad35K++ in combination with

  15. Studies on the Th biodistribution in internal contamination by the fission track method using animals

    International Nuclear Information System (INIS)

    Ciubotariu, M.; Danis, A.; Dumitrescu, G.; Cucu, M.

    1998-01-01

    In our previous studies on the U internal contamination, qualitative and quantitative results were obtained by using the fission track methods. In order to obtain complete data on the fissionable element internal contamination using animals, we started a similar study using Th as contaminating element and Wistar London breed rats as laboratory animals. Different ways to obtain internal contaminations were investigated: ingestion, inhalation, absorption by skin and through wounds. In this stage, Wistar-London breed rats of the same sex, weight and age were internal contaminated by 1 ml Th solution ingestion for each rat corresponding to an Annual Limit Intake.The animals were kept in normal life conditions and under permanent medical surveillance up to their sacrifice. Also, their evacuations where sampled every 24 hours. They were sacrificed at different time intervals after their contamination: 2 days (RAT 1), 7 days (RAT 2) and 14 days (RAT 3). After sacrifice, their vital organs were sampled, weighed, calcined, reweighed and finally analysed by track detection using the fission track micromapping technique. This technique was used in the following conditions: - mica-muscovite as track detector pre-etched for fossil tracks 18 h in HF; - the neutron irradiations were performed in the nuclear reactor VVR-S Bucharest at the neutron fluences of 3x10 15 - 2x10 16 fast neutrons/cm 2 . In order to check whether there is any U contribution to the fission track densities obtained in track detectors, U existing in the rat body due to food and water, the neutron irradiations of the ensembles were performed with and without 1 mm Cd shielding; - the visualization of the Th induced fission tracks were obtained by chemical etching in HF, 3 h at room temperature; - the Th track micromappings obtained in track detectors were studied by optical microscopy using a stereomicroscope WILD M7S for ensemble study (X6-X31) and a binocular ZEISS JENA microscope for qualitative and

  16. In vitro radio autographic studies of the biodistribution of radiopharmaceuticals on blood elements

    International Nuclear Information System (INIS)

    Eipoll-Hamer, E.; De Paula, E.F.; Freitas, L.C.; Pereira, M.J.S.; Carvalho, J.J.; Porto, L.C.M.S.; Fonseca, L.M.; Gutfilen, B.; Bernardo Filho, M.

    1998-01-01

    In the present study we evaluated the binding of the radiopharmaceuticals sodium pertechnetate (Na 99m Tc O 4 ), methylene-diphosphonic acid ( 99m Tc-M D P) and glucoheptonate acid ( 99m Tc-G H A) to blood elements using centrifugation and radio autographic techniques. Heparinized blood was incubated with the labelled compounds for 0,1,2,3,4, 6 and 24 h. Plasma (P) and blood cells (B C) were isolated and precipitated with 5% trichloroacetic acid (TCA), and soluble (S F) and insoluble fractions (IF) were separated. Blood samples were prepared (0 and 24 h) and coated with Lm-1 radio autographic emulsions and percent radioactivity (%rad) in P and B C was determined. The binding of Na 99m Tc O 4 (5 rad) to P was 61.2 (0 h) and 46.0% (24 h), and radioautography showed 63.7% (0 h) and 43.3% (24 h). The binding to B C was 38.8% (0 h) and 54.0% (24 h), and radioautography showed 36.3% (0 h) and 56.7% (24 h). 99m Tc-M D P study presented 91.1% (0 h) to P and 87.2%(24 h), and radioautography showed presented 91.1% (0 h) to P and 87.2% (24 h), and radioautography showed 67.9% (0 h) and 67.4% (24 h). The binding to B C was 8.9% (0 h) and 12.8% (24 h), and radioautography showed 32.1% (0 h) and 32.6% (24 h). 99m Tc-G H A study was 90.1% (0 h) to P and 79.9% (24 h), and radioautography showed 67.2% (0 h) and 60.1% (24 h). The binding to B C was 9.9% (0 h) and 20.1% (24 h), and radioautography showed 32.8% (0 h) and 39.9% (24 h). The comparison of the obtained results suggests that the binding to plasma and blood cells in the two techniques used (radioautography and centrifugation) is qualitatively in accordance. (author)

  17. In vitro radioautographic studies of the biodistribution of radiopharmaceuticals on blood elements

    Directory of Open Access Journals (Sweden)

    Ripoll-Hamer E.

    1998-01-01

    Full Text Available In the present study we evaluated the binding of the radiopharmaceuticals sodium pertechnetate (Na 99mTcO4, methylenediphosphonic acid (99mTc-MDP and glucoheptonate acid (99mTc-GHA to blood elements using centrifugation and radioautographic techniques. Heparinized blood was incubated with the labelled compounds for 0, 1, 2, 3, 4, 6 and 24 h. Plasma (P and blood cells (BC were isolated and precipitated with 5% trichloroacetic acid (TCA, and soluble (SF and insoluble fractions (IF were separated. Blood samples were prepared (0 and 24 h and coated with LM-1 radioautographic emulsions and percent radioactivity (%rad in P and BC was determined. The binding of Na 99mTcO4 (%rad to P was 61.2% (0 h and 46.0% (24 h, and radioautography showed 63.7% (0 h and 43.3% (24 h. The binding to BC was 38.8% (0 h and 54.0% (24 h, and radioautography showed 36.3% (0 h and 56.7% (24 h. 99mTc-MDP study presented 91.1% (0 h to P and 87.2% (24 h, and radioautography showed 67.9% (0 h and 67.4% (24 h. The binding to BC was 8.9% (0 h and 12.8% (24 h, and radioautography showed 32.1% (0 h and 32.6% (24 h. 99mTc-GHA study was 90.1% (0 h to P and 79.9% (24 h, and radioautography showed 67.2% (0 h and 60.1% (24 h. The binding to BC was 9.9% (0 h and 20.1% (24 h, and radioautography showed 32.8% (0 h and 39.9% (24 h. The comparison of the obtained results suggests that the binding to plasma and blood cells in the two techniques used (radioautography and centrifugation is qualitatively in accordance

  18. Comparison of two methods of quantitation in human studies of biodistribution and radiation dosimetry

    International Nuclear Information System (INIS)

    Smith, T.

    1992-01-01

    A simple method of quantitating organ radioactivity content for dosimetry purposes based on relationships between organ count rate and the initial whole body count rate, has been compared with a more rigorous method of absolute quantitation using a transmission scanning technique. Comparisons were on the basis of organ uptake (% administered activity) and resultant organ radiation doses (mGy MBq -1 ) in 6 normal male volunteers given a 99 Tc m -labelled myocardial perfusion imaging agent intravenously at rest and following exercise. In these studies, estimates of individual organ uptakes by the simple method were in error by between +24 and -16% compared with the more accurate method. However, errors on organ dose values were somewhat less and the effective dose was correct to within 3%. (Author)

  19. Biodistribution study of carbogenic dots in cells and in vivo for optical imaging

    International Nuclear Information System (INIS)

    Li Nan; Liang Xiaofei; Wang Lili; Li Zonghai; Li Peiyong; Zhu Yihua; Song Jing

    2012-01-01

    Blue fluorescent carbon dots (C-dots) were synthesized and evaluated for their cytotoxicity and also for their optical imaging performance. The results showed that the C-dots could enter into the Hela cells in 15 min incubation and the uptake increased rapidly from 15 min to 2 h. In cytotoxicity study, C-dots were biocompatible and nontoxic to three human cells including two cancer cells (Hela and SMCC-7721) and one normal cell (HEK 293) in concentrations up to 500 μg/mL. Since the endocytic interference factors, including NaN 3 , MβCD, sucrose, and low temperature, could not play an inhibitory effect on C-dots entering into cells, the direct nonendocytic pathway for C-dots was speculated. The C-dots showed encouraging cell-imaging applications in vitro and in vivo. They entered into cells without any further functionalization, and the fluorescence property of these particles can be used for fluorescence-based cell-imaging applications.

  20. Study of {sup 99m}Tc-DMSA biodistribution in experimental animals

    Energy Technology Data Exchange (ETDEWEB)

    Castro, Thais O.M. de; Silva, Natanael G. da; Colturato, Maria T.; Felgueiras, Carlos F.; Mengatti, Jair; Fukumori, Neuza T.O.; Matsuda, Margareth M.N.; Araújo, Elaine B. de, E-mail: thais.castrom@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Radiofarmacia

    2017-11-01

    {sup 99m}Tc-DMSA, succimer ({sup 99m}Tc), is a radiopharmaceutical commonly used in nuclear medicine for renal function evaluation by imaging. In order to achieve adequate labeling of the product with good radiochemical yield and standardized biological distribution, the interval of 185 - 3700 MBq should be kept in a maximum volume of 3 mL for product labeling. Moreover, one should avoid exposing the reconstituted solution to oxygen and using the product after four hours post labeling. The aim of the study was to quantify and evaluate the influence of different DMSA complexes on biological distribution of the radiopharmaceutical in experimental animals, taking in account variations in the labeling parameters. Radiochemical purity was determined by paper and thin layer chromatography using both acetone/Whatman 3MM, 0.9% NaCl/TLC-SG and n-propanol/ H{sub 2}O/acetic acid (4:3:1 V/V/V)/TLC-SG systems respectively for quantification of {sup 99m}TcO{sub 4} - and {sup 99m}TcO{sub 2} plus some {sup 99m}Tc-DMSA complexes. The labeling activity did not significantly affect the extent of the main complex generation. The presence of oxygen and the concentration of {sup 99}Tc did not markedly change the percentage of the radiochemical impurities in the preparation. Radiochemical purity tests of the DMSA-{sup 99m}Tc based on IPEN-CNEN DMSA-TEC reagent and on another producer's reagent showed similar results. Although the routine method used by IPEN-CNEN to determine the radiochemical yield of {sup 99m}Tc-DMSA was not able to discriminate among {sup 99m}Tc-DMSA complexes, the renal uptake and the kidney to liver plus spleen uptake ratio in rats met the official compendia criteria for the radiopharmaceutical. (author)

  1. Study of "9"9"mTc-DMSA biodistribution in experimental animals

    International Nuclear Information System (INIS)

    Castro, Thais O.M. de; Silva, Natanael G. da; Colturato, Maria T.; Felgueiras, Carlos F.; Mengatti, Jair; Fukumori, Neuza T.O.; Matsuda, Margareth M.N.; Araújo, Elaine B. de

    2017-01-01

    "9"9"mTc-DMSA, succimer ("9"9"mTc), is a radiopharmaceutical commonly used in nuclear medicine for renal function evaluation by imaging. In order to achieve adequate labeling of the product with good radiochemical yield and standardized biological distribution, the interval of 185 - 3700 MBq should be kept in a maximum volume of 3 mL for product labeling. Moreover, one should avoid exposing the reconstituted solution to oxygen and using the product after four hours post labeling. The aim of the study was to quantify and evaluate the influence of different DMSA complexes on biological distribution of the radiopharmaceutical in experimental animals, taking in account variations in the labeling parameters. Radiochemical purity was determined by paper and thin layer chromatography using both acetone/Whatman 3MM, 0.9% NaCl/TLC-SG and n-propanol/ H_2O/acetic acid (4:3:1 V/V/V)/TLC-SG systems respectively for quantification of "9"9"mTcO_4 - and "9"9"mTcO_2 plus some "9"9"mTc-DMSA complexes. The labeling activity did not significantly affect the extent of the main complex generation. The presence of oxygen and the concentration of "9"9Tc did not markedly change the percentage of the radiochemical impurities in the preparation. Radiochemical purity tests of the DMSA-"9"9"mTc based on IPEN-CNEN DMSA-TEC reagent and on another producer's reagent showed similar results. Although the routine method used by IPEN-CNEN to determine the radiochemical yield of "9"9"mTc-DMSA was not able to discriminate among "9"9"mTc-DMSA complexes, the renal uptake and the kidney to liver plus spleen uptake ratio in rats met the official compendia criteria for the radiopharmaceutical. (author)

  2. Quantum dots in axillary lymph node mapping: Biodistribution study in healthy mice

    Directory of Open Access Journals (Sweden)

    Guillemin François

    2008-04-01

    Full Text Available Abstract Background Breast cancer is the first cause of cancer death among women and its incidence doubled in the last two decades. Several approaches for the treatment of these cancers have been developed. The axillary lymph node dissection (ALND leads to numerous morbidity complications and is now advantageously replaced by the dissection and the biopsy of the sentinel lymph node. Although this approach has strong advantages, it has its own limitations which are manipulation of radioactive products and possible anaphylactic reactions to the dye. As recently proposed, these limitations could in principle be by-passed if semiconductor nanoparticles (quantum dots or QDs were used as fluorescent contrast agents for the in vivo imaging of SLN. QDs are fluorescent nanoparticles with unique optical properties like strong resistance to photobleaching, size dependent emission wavelength, large molar extinction coefficient, and good quantum yield. Methods CdSe/ZnS core/shell QDs emitting around 655 nm were used in our studies. 20 μL of 1 μM (20 pmol QDs solution were injected subcutaneously in the anterior paw of healthy nude mice and the axillary lymph node (ALN was identified visually after injection of a blue dye. In vivo fluorescence spectroscopy was performed on ALN before the mice were sacrificed at 5, 15, 30, 60 min and 24 h after QDs injection. ALN and all other organs were removed, cryosectioned and observed in fluorescence microscopy. The organs were then chemically made soluble to extract QDs. Plasmatic, urinary and fecal fluorescence levels were measured. Results QDs were detected in ALN as soon as 5 min and up to 24 h after the injection. The maximum amount of QDs in the ALN was detected 60 min after the injection and corresponds to 2.42% of the injected dose. Most of the injected QDs remained at the injection site. No QDs were detected in other tissues, plasma, urine and feces. Conclusion Effective and rapid (few minutes detection of

  3. Radiohalogenation of biomolecules. An experimental study on radiohalogen preparation, precursor synthesis, radiolabeling and biodistribution

    International Nuclear Information System (INIS)

    Koziorowski, J.

    1998-01-01

    Radiohalogens are widely used in nuclear medicine, both as tool for diagnostic in vivo imaging, and in radionuclide therapy. This study deals with the use of radiohalogens; separation, precursor synthesis, labeling and biological behavior. The focus is on 211 At and 124 I, the former being a candidate for nuclide therapy and the latter potentially useful for diagnostic imaging and Auger-electron based radiotherapy. For astatine the separation, labeling and some biological behavior is described, and for iodine the latter two. Astatine was separated from an irradiated bismuth target by dry distillation. A novel cryotrap was developed for the isolation of astatine and subsequent synthesis of radiolabeled compounds. 5-[ 211 At]astato-2'-deoxyuridine (AUdR) and N-succinimidyl-4-[ 211 At]astatobenzoate (SAB) were synthesized in 95% respectively 90% radiochemical yields. The former is incorporated into DNA of proliferating cells and can therefore be used as an endoradiotherapeutic agent. The latter is a conjugate for the astatination of proteins. Human epidermal growth factor (hEGF) was tagged with astatine using three approaches: a) direct labeling of native hEGF, b) conjugation with SAB, and c) direct labeling of an hEGF - 7-(3-aminopropyl)-7,8-dicarba-nido-undecaborate(1-) conjugate. The overall labeling yields were 3.5% for direct labeling, 44% for SAB and 70% for the hEGF-nido-carborane conjugate. A new route to N-succinimidyl 3- and 4- [ 124 I]iodobenzoate, two reagents for radioiodination of proteins is described affording 90% radiochemical yield. Three radioiodinated analogs of PK11195, 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)isoquinoline-3-carboxyam ide, a peripheral-type benzodiazepine receptor antagonist, were synthesized. All three analogs were obtained in >90% radiochemical yield. Synthesis and application of 5-[ 124 I]iodo-2'-deoxyuridine (IUdR) is presented. The closo-dodecaborate anion was evaluated as prosthetic group for radioiodination of

  4. Quantum dots in axillary lymph node mapping: Biodistribution study in healthy mice

    International Nuclear Information System (INIS)

    Robe, Anne; Pic, Emilie; Lassalle, Henri-Pierre; Bezdetnaya, Lina; Guillemin, François; Marchal, Frédéric

    2008-01-01

    Breast cancer is the first cause of cancer death among women and its incidence doubled in the last two decades. Several approaches for the treatment of these cancers have been developed. The axillary lymph node dissection (ALND) leads to numerous morbidity complications and is now advantageously replaced by the dissection and the biopsy of the sentinel lymph node. Although this approach has strong advantages, it has its own limitations which are manipulation of radioactive products and possible anaphylactic reactions to the dye. As recently proposed, these limitations could in principle be by-passed if semiconductor nanoparticles (quantum dots or QDs) were used as fluorescent contrast agents for the in vivo imaging of SLN. QDs are fluorescent nanoparticles with unique optical properties like strong resistance to photobleaching, size dependent emission wavelength, large molar extinction coefficient, and good quantum yield. CdSe/ZnS core/shell QDs emitting around 655 nm were used in our studies. 20 μL of 1 μM (20 pmol) QDs solution were injected subcutaneously in the anterior paw of healthy nude mice and the axillary lymph node (ALN) was identified visually after injection of a blue dye. In vivo fluorescence spectroscopy was performed on ALN before the mice were sacrificed at 5, 15, 30, 60 min and 24 h after QDs injection. ALN and all other organs were removed, cryosectioned and observed in fluorescence microscopy. The organs were then chemically made soluble to extract QDs. Plasmatic, urinary and fecal fluorescence levels were measured. QDs were detected in ALN as soon as 5 min and up to 24 h after the injection. The maximum amount of QDs in the ALN was detected 60 min after the injection and corresponds to 2.42% of the injected dose. Most of the injected QDs remained at the injection site. No QDs were detected in other tissues, plasma, urine and feces. Effective and rapid (few minutes) detection of sentinel lymph node using fluorescent imaging of quantum dots was

  5. BOPP revisited. A study on the toxicity, biodistribution and convection enhanced delivery of BOPP in the 9L intracerebral rat glioma model

    International Nuclear Information System (INIS)

    Kahl, S.B.; Koo, M.-S.; Ozawa, T.; Afzal, J.; Lamborn, K.R.; Deen, D.F.; Bollen, A.W.; Bauer, W.F.

    2006-01-01

    To evaluate and compare the toxicity and boron biodistribution of the boronated porphyrin BOPP when administered by either intravenous or convection enhanced delivery (CED). For the toxicity study, Fischer 344 rats were injected with graded concentrations of BOPP into the tail vein. For boron biodistribution studies, 9L tumor-bearing rats received BOPP either systematically or by CED. When given i.v. BOPP showed unacceptable toxicity in normal rats receiving doses of ≥60 mg/kg. In contrast, tumor bearing rats receiving BOPP by CED showed no evidence of toxic effects whatsoever. In the biodistribution study, the maximum tumor boron concentration was ∼21 μ/g at 48 h after i.v. injection, at which time the tumor/blood ratio was ∼1.2. Neither of these values is optimal. However, when BOPP was delivered directly into intracerebral tumors with CED, we obtained tumor boron concentrations much greater than those obtained by i.v. injection. For example, convection enhanced delivery of 1.5 mg BOPP produced an average tumor boron level of 519 μg/g and a tumor/blood ratio of ∼1850:1. Tumor/brain ratios of ∼9:1 (ipsilateral) and ∼41:1 (contralateral) were also found at this dose. We conclude that changing the method of BOPP delivery from i.v. to CED significantly enhances the boron concentration in tumors and produces very favorable tumor/blood and tumor/brain ratios with no concomittant systemic toxicity. (author)

  6. Liposome-encapsulated EF24-HPβCD inclusion complex: a preformulation study and biodistribution in a rat model

    International Nuclear Information System (INIS)

    Agashe, H.; Lagisetty, P.; Sahoo, K.; Bourne, D.; Grady, B.; Awasthi, V.

    2011-01-01

    3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a “drug-in-CD-in liposome” approach. An aqueous solution of EF24 and hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze–thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HPβCD mixture provided k 1:1 value of 9.9 M −1 . The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HPβCD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 ± 2.6 nm) by dehydration–rehydration technique. With extrusion technique, the size of 177 ± 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 μM dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an α-t 1/2 of 21.4 min and β-t 1/2 of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using “drug-in-CD-in liposome” approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

  7. Liposome-encapsulated EF24-HPβCD inclusion complex: a preformulation study and biodistribution in a rat model

    Science.gov (United States)

    Agashe, H.; Lagisetty, P.; Sahoo, K.; Bourne, D.; Grady, B.; Awasthi, V.

    2011-06-01

    3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a "drug-in-CD-in liposome" approach. An aqueous solution of EF24 and hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze-thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HPβCD mixture provided k 1:1 value of 9.9 M-1. The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HPβCD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 ± 2.6 nm) by dehydration-rehydration technique. With extrusion technique, the size of 177 ± 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 μM dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an α- t 1/2 of 21.4 min and β- t 1/2 of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using "drug-in-CD-in liposome" approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

  8. Liposome-encapsulated EF24-HP{beta}CD inclusion complex: a preformulation study and biodistribution in a rat model

    Energy Technology Data Exchange (ETDEWEB)

    Agashe, H; Lagisetty, P; Sahoo, K; Bourne, D [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States); Grady, B [School of Chemical, Biological and Materials Engineering (United States); Awasthi, V [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States)

    2011-06-15

    3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a 'drug-in-CD-in liposome' approach. An aqueous solution of EF24 and hydroxypropyl-{beta}-cyclodextrin (HP{beta}CD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze-thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HP{beta}CD mixture provided k{sub 1:1} value of 9.9 M{sup -1}. The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HP{beta}CD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 {+-} 2.6 nm) by dehydration-rehydration technique. With extrusion technique, the size of 177 {+-} 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 {mu}M dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an {alpha}-t{sub 1/2} of 21.4 min and {beta}-t{sub 1/2} of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using 'drug-in-CD-in liposome' approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

  9. Biodistribution and receptor imaging studies of insulin labelled with radioiodine in mice bearing H22 hepatocellular cacinoma

    International Nuclear Information System (INIS)

    Tang Gongshun; Kuang Anren; Liang Zenlu

    2004-01-01

    Objectives: It has been demonstrated that insulin receptor of hepatocellular carcinoma cells is overexpression. The biodistribution of 125I-insulin and receptor imaging studies of 131I-insulin in mice bearing solid liver tumor comprised of hepatic carcinoma H22 cells were performed to develop insulin as a carder of radioiodine. Methods: 1 )Insulin was radiolabeled with iodine-125 or iodine-131 using a Chloramines T method. Twenty mice bearing tumor were divided into 4 groups (n = 5 each) randomly. They were killed at 5, 15, 30, 60 min after 125I-insulin administered intravenously. The percentage of injected dose of 125I-insulin per gram of tissue(%ID/gdis) in mice bearing tumor were determined. 2) Another ten mice bearing tumor were selected to be as a inhibition group. They received cold insulin 2 mg intravenously 2 min ahead of administration of 125I-insulin and they were killed at 30 min (n=5) and 60 rain (n=5) randomly post 125I-insulin injection. The %ID/ginh and the inhibited rates[(%ID/gdis-%iD/ginh) %ID/gdis 100%] were obtained. 3) One tumor-mouse received 7.4 Mbq 13II-insulin intravenously, another received cold insulin 2 mg injection before 13II-insulin injection. Whole body images were carded out and the radioactivity ratios of tumor/normal were accounted at 60 min. Results: 1) The radiochemical purities of 125I-insulin and 13II-insulin were 96.7%-98.9%. The tumors uptake of the 125I-insulin increased gradually, its peak (%ID/gdis) was 3.44% 0.42% at 30 min, when the normal tissues uptake decreased sharply post-injection. The radioactivity ratio of the tumor/blood and tumor/muscle reached to 1.44 and 3.62 respectively at 60 min. 2)The tumor-inhibition rate was 32.07% at 30 min and 37.42% at 60 min. 3) A high radioactivity accumulation in tumor region could be seen in the mouse at 60 min post 131I-insulin injection. The radioactivity ratio of the tumor/normal tissue was 2.13 and it declined to 1.37 after received insulin 2 mg intervention. Conclusions

  10. Liposome-encapsulated EF24-HP{beta}CD inclusion complex: a preformulation study and biodistribution in a rat model

    Energy Technology Data Exchange (ETDEWEB)

    Agashe, H.; Lagisetty, P.; Sahoo, K.; Bourne, D. [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States); Grady, B. [School of Chemical, Biological and Materials Engineering (United States); Awasthi, V., E-mail: vawasthi@ouhsc.edu [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States)

    2011-06-15

    3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a 'drug-in-CD-in liposome' approach. An aqueous solution of EF24 and hydroxypropyl-{beta}-cyclodextrin (HP{beta}CD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze-thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HP{beta}CD mixture provided k{sub 1:1} value of 9.9 M{sup -1}. The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HP{beta}CD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 {+-} 2.6 nm) by dehydration-rehydration technique. With extrusion technique, the size of 177 {+-} 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 {mu}M dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an {alpha}-t{sub 1/2} of 21.4 min and {beta}-t{sub 1/2} of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using 'drug-in-CD-in liposome' approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

  11. Boron neutron capture therapy for clear cell sarcoma (CCS): biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models.

    Science.gov (United States)

    Andoh, T; Fujimoto, T; Sudo, T; Fujita, I; Imabori, M; Moritake, H; Sugimoto, T; Sakuma, Y; Takeuchi, T; Kawabata, S; Kirihata, M; Akisue, T; Yayama, K; Kurosaka, M; Miyatake, S; Fukumori, Y; Ichikawa, H

    2011-12-01

    Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake l-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of (10)B (45-74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg). Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Boron neutron capture therapy for clear cell sarcoma (CCS): Biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models

    Energy Technology Data Exchange (ETDEWEB)

    Andoh, T. [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Fujimoto, T. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Sudo, T. [Section of Translational Research, Hyogo Cancer Center, Akashi 673-0021 (Japan); Fujita, I.; Imabori, M. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Moritake, H. [Department of Pediatrics, Miyazaki University, Kiyotake 889-1692 (Japan); Sugimoto, T. [Department of Pediatrics, Saiseikai Shigaken Hospital, Ritto 520-3046 (Japan); Sakuma, Y. [Department of Pathology, Hyogo Cancer Center, Akashi 673-0021 (Japan); Takeuchi, T. [Department of Pathology, Kochi University, Nangoku 783-8505 (Japan); Kawabata, S. [Department of Neurosurgery, Osaka Medical College, Osaka 569-8686 (Japan); Kirihata, M. [Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai 599-8531 (Japan); Akisue, T. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Yayama, K. [Laboratory of Cardiovascular Pharmacology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Kurosaka, M. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Miyatake, S. [Department of Neurosurgery, Osaka Medical College, Osaka 569-8686 (Japan); Fukumori, Y. [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Ichikawa, H., E-mail: ichikawa@pharm.kobegakuin.ac.jp [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan)

    2011-12-15

    Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake L-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of {sup 10}B (45-74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg).

  13. Boron neutron capture therapy for clear cell sarcoma (CCS): Biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models

    International Nuclear Information System (INIS)

    Andoh, T.; Fujimoto, T.; Sudo, T.; Fujita, I.; Imabori, M.; Moritake, H.; Sugimoto, T.; Sakuma, Y.; Takeuchi, T.; Kawabata, S.; Kirihata, M.; Akisue, T.; Yayama, K.; Kurosaka, M.; Miyatake, S.; Fukumori, Y.; Ichikawa, H.

    2011-01-01

    Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake L-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of 10 B (45–74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg).

  14. Biodistribution and toxicological study of PEGylated single-wall carbon nanotubes in the zebrafish (Danio rerio) nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Gisele E.B.; Dal Bosco, Lidiane [Laboratório de Neurociências, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande (FURG), Rio Grande, RS, 96210-900 (Brazil); Programa de Pós-graduação em Ciências Fisiológicas–Fisiologia Animal Comparada, FURG, Rio Grande, RS, 96210-900 (Brazil); Gonçalves, Carla O.F.; Santos, Adelina P. [Laboratório de Química de Nanoestruturas, Centro de Desenvolvimento da Tecnologia Nuclear, Belo Horizonte, MG, 31270-901 (Brazil); Fantini, Cristiano [Instituto de Ciências Exatas, Departamento de Física, Belo Horizonte, MG, 31270-901 (Brazil); Furtado, Clascídia A. [Laboratório de Química de Nanoestruturas, Centro de Desenvolvimento da Tecnologia Nuclear, Belo Horizonte, MG, 31270-901 (Brazil); Parfitt, Gustavo M.; Peixoto, Carolina [Laboratório de Neurociências, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande (FURG), Rio Grande, RS, 96210-900 (Brazil); Programa de Pós-graduação em Ciências Fisiológicas–Fisiologia Animal Comparada, FURG, Rio Grande, RS, 96210-900 (Brazil); Romano, Luis Alberto [Instituto de Oceanografía, Universidade Federal do Rio Grande, Rio Grande, RS, 96210-030 (Brazil); and others

    2014-11-01

    Nanotechnology has been proven to be increasingly compatible with pharmacological and biomedical applications. Therefore, we evaluated the biological interactions of single-wall carbon nanotubes functionalized with polyethylene glycol (SWNT-PEG). For this purpose, we analyzed biochemical, histological, behavioral and biodistribution parameters to understand how this material behaves in vitro and in vivo using the fish Danio rerio (zebrafish) as a biological model. The in vitro results for fish brain homogenates indicated that SWNT-PEG had an effect on lipid peroxidation and GSH (reduced glutathione) content. However, after intraperitoneal exposure, SWNT-PEG proved to be less biocompatible and formed aggregates, suggesting that the PEG used for the nanoparticle functionalization was of an inappropriate size for maintaining product stability in a biological environment. This problem with functionalization may have contributed to the low or practically absent biodistribution of SWNT-PEG in zebrafish tissues, as verified by Raman spectroscopy. There was an accumulation of material in the abdominal cavity that led to inflammation and behavioral disturbances, as evaluated by a histological analysis and an open field test, respectively. These results provide evidence of a lack of biocompatibility of SWNTs modified with short chain PEGs, which leads to the accumulation of the material, tissue damage and behavioral alterations in the tested subjects. - Highlights: • In vitro brain exposure diminished lipid peroxidation. • In vitro brain exposure depletes the GSH content. • SWNT-PEG was not biocompatible and formed aggregates after the exposure. • Practically absent biodistribution of SWNT-PEG was observed by Raman spectroscopy. • SWNT-PEG exposure lead to tissue damage and inflammatory responses.

  15. Biodistribution and toxicological study of PEGylated single-wall carbon nanotubes in the zebrafish (Danio rerio) nervous system

    International Nuclear Information System (INIS)

    Weber, Gisele E.B.; Dal Bosco, Lidiane; Gonçalves, Carla O.F.; Santos, Adelina P.; Fantini, Cristiano; Furtado, Clascídia A.; Parfitt, Gustavo M.; Peixoto, Carolina; Romano, Luis Alberto

    2014-01-01

    Nanotechnology has been proven to be increasingly compatible with pharmacological and biomedical applications. Therefore, we evaluated the biological interactions of single-wall carbon nanotubes functionalized with polyethylene glycol (SWNT-PEG). For this purpose, we analyzed biochemical, histological, behavioral and biodistribution parameters to understand how this material behaves in vitro and in vivo using the fish Danio rerio (zebrafish) as a biological model. The in vitro results for fish brain homogenates indicated that SWNT-PEG had an effect on lipid peroxidation and GSH (reduced glutathione) content. However, after intraperitoneal exposure, SWNT-PEG proved to be less biocompatible and formed aggregates, suggesting that the PEG used for the nanoparticle functionalization was of an inappropriate size for maintaining product stability in a biological environment. This problem with functionalization may have contributed to the low or practically absent biodistribution of SWNT-PEG in zebrafish tissues, as verified by Raman spectroscopy. There was an accumulation of material in the abdominal cavity that led to inflammation and behavioral disturbances, as evaluated by a histological analysis and an open field test, respectively. These results provide evidence of a lack of biocompatibility of SWNTs modified with short chain PEGs, which leads to the accumulation of the material, tissue damage and behavioral alterations in the tested subjects. - Highlights: • In vitro brain exposure diminished lipid peroxidation. • In vitro brain exposure depletes the GSH content. • SWNT-PEG was not biocompatible and formed aggregates after the exposure. • Practically absent biodistribution of SWNT-PEG was observed by Raman spectroscopy. • SWNT-PEG exposure lead to tissue damage and inflammatory responses

  16. Boron nitride nanotubes radiolabeled with ⁹⁹mTc: preparation, physicochemical characterization, biodistribution study, and scintigraphic imaging in Swiss mice.

    Science.gov (United States)

    Soares, Daniel Crístian Ferreira; Ferreira, Tiago Hilário; Ferreira, Carolina de Aguiar; Cardoso, Valbert Nascimento; de Sousa, Edésia Martins Barros

    2012-02-28

    In the present study, boron nitride nanotubes (BNNTs) were synthesized from an innovative process and functionalized with a glycol chitosan polymer in CDTN (Centro de Desenvolvimento da Tecnologia Nuclear) laboratories. As a means of studying their in vivo biodistribution behavior, these nanotubes were radiolabeled with (99m)Tc and injected in mice. Their size, distribution, and homogeneity were determined by photon correlation spectroscopy (PCS), while their zeta potential was determined by laser Doppler anemometry. The morphology and structural organization were evaluated by scanning electron microscopy (SEM). The functionalization in the nanotubes was evaluated by thermogravimetry analysis (TGA) and Fourier transformer infrared spectroscopy. The results showed that BNNTs were obtained and functionalized successfully, reaching a mean size and dispersity deemed adequate for in vivo studies. The BNNTs were also evaluated by ex vivo biodistribution studies and scintigraphic imaging in healthy mice. The results showed that nanostructures, after 24h, having accumulated in the liver, spleen and gut, and eliminated via renal excretion. The findings from this study reveal a potential application of functionalized BNNTs as new potential drugs or radioisotope nanocarriers to be applied in therapeutic procedures. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. [Electrophysiological study on rat conduit pulmonary artery smooth muscle cells under normoxia and acute hypoxia].

    Science.gov (United States)

    Hu, Ying; Zou, Fei; Cai, Chun-Qing; Wu, Hang-Yu; Yun, Hai-Xia; Chen, Yun-Tian; Jin, Guo-En; Ge, Ri-Li

    2006-10-25

    The present study was designed to investigate the electrophysiological characteristics of rat conduit pulmonary artery smooth muscle cells (PASMCs) and the response to acute hypoxia. PASMCs of the 1st to 2nd order branches in the conduit pulmonary arteries were obtained by enzymatic isolation. The PASMCs were divided into acute hypoxia preconditioned group and normoxia group. Hypoxia solutions were achieved by bubbling with 5% CO2 plus 95% N2 for at least 30 min before cell perfusion. Potassium currents were compared between these two groups using whole-cell patch clamp technique. The total outward current of PASMCs was measured under normoxia condition when iBTX [specific blocking agent of large conductance Ca-activated K(+) (BK(Ca)) channel] and 4-AP [specific blocking agent of delayed rectifier K(+) (K(DR)) channel] were added consequently into bath solution. PASMCs were classified into three types according to their size, shape and electrophysiological characteristics. Type I cells are the smallest with spindle shape, smooth surface and discrete perinuclear bulge. Type II cells show the biggest size with banana-like appearance. Type III cells have the similar size with type I, and present intermediary shape between type I and type II. iBTX had little effect on the total outward current in type I cells, while 4-AP almost completely blocked it. Most of the total outward current in type II cells was inhibited by iBTX, and the remaining was sensitive to 4-AP. In type III cells, the total outward current was sensitive to both iBTX and 4-AP. Acute hypoxia reduced the current in all three types of cells: (1614.8+/-62.5) pA to (892.4+/-33.6) pA for type I cells (Ppotassium current and improves the E(m) in PASMCs. These effects may be involved in the modulation of constriction/relaxation of conduit artery under acute hypoxia. Different distribution of K(DR) and BK(Ca) channels in these three types of PASMCs might account for their different constriction

  18. Cognitive training and selective attention in the aging brain: an electrophysiological study.

    Science.gov (United States)

    O'Brien, Jennifer L; Edwards, Jerri D; Maxfield, Nathan D; Peronto, Carol L; Williams, Victoria A; Lister, Jennifer J

    2013-11-01

    Age-related deficits in selective attention are hypothesized to result from decrements in inhibition of task-irrelevant information. Speed of processing (SOP) training is an adaptive cognitive intervention designed to enhance processing speed for attention tasks. The effectiveness of SOP training to improve cognitive and everyday functional performance is well documented. However, underlying mechanisms of these training benefits are unknown. Participants completed a visual search task evaluated using event-related potentials (ERPs) before and after 10 weeks of SOP training or no contact. N2pc and P3b components were evaluated to determine SOP training effects on attentional resource allocation and capacity. Selective attention to a target was enhanced after SOP training compared to no training. N2pc and P3b amplitudes increased after training, reflecting attentional allocation and capacity enhancement, consistent with previous studies demonstrating behavioral improvements in selective attention following SOP training. Changes in ERPs related to attention allocation and capacity following SOP training support the idea that training leads to cognitive enhancement. Specifically, we provide electrophysiological evidence that SOP training may be successful in counteracting age-related declines in selective attention. This study provides important evidence of the underlying mechanisms by which SOP training improves cognitive function in older adults. Published by Elsevier Ireland Ltd.

  19. Synthesis and study of bio-distribution of a piperidine derivative marked by the technetium 99m

    International Nuclear Information System (INIS)

    Guizani, Sihem

    2008-01-01

    With the increase in life expectancy and ageing, the cerebral diseases, became among the first causes of mortality of the population. However, the prevention and the treatment of these diseases depend on the diagnosis and an early and reliable assessment. The radio pharmaceutics used are very few. The object of our work concerns the development of a new radiotracer labelled with the Tc 99m, it's a piperidine derivative (the 1 piperidine-1-yl ferrocene-1-one), then to follow the kinetics and its biodistribution in rats to detect its targets. The follow-up of kinetics and the biodistribution of the lately synthesized molecule after their injection, revealed a cerebral activity of 0.82 pour cent. This value represents a sufficient quantity to be detected by an external device of acquisition of radioactivity like gamma camera without health threatens of the patient. The method of labelling developed opens a new way of synthesis of characterized by radiochemical stability and a very promising biochemical behavior for the cerebral radiodiagnosis. (Author)

  20. Site of anticonvulsant action on sodium channels: autoradiographic and electrophysiological studies in rat brain

    International Nuclear Information System (INIS)

    Worley, P.F.; Baraban, J.M.

    1987-01-01

    The anticonvulsants phenytoin and carbamazepine interact allosterically with the batrachotoxin binding site of sodium channels. In the present study, we demonstrate an autoradiographic technique to localize the batrachotoxin binding site on sodium channels in rat brain using [ 3 H]batrachotoxinin-A 20-alpha-benzoate (BTX-B). Binding of [ 3 H]BTX-B to brain sections is dependent on potentiating allosteric interactions with scorpion venom and is displaced by BTX-B (Kd approximately 200 nM), aconitine, veratridine, and phenytoin with the same rank order of potencies as described in brain synaptosomes. The maximum number of [ 3 H]BTX-B binding sites in forebrain sections also agrees with biochemical determinations. Autoradiographic localizations indicate that [ 3 H]BTX-B binding sites are not restricted to cell bodies and axons but are present in synaptic zones throughout the brain. For example, a particularly dense concentration of these sites in the substantia nigra is associated with afferent terminals of the striatonigral projection. By contrast, myelinated structures possess much lower densities of binding sites. In addition, we present electrophysiological evidence that synaptic transmission, as opposed to axonal conduction, is preferentially sensitive to the action of aconitine and veratridine. Finally, the synaptic block produced by these sodium channel activators is inhibited by phenytoin and carbamazepine at therapeutic anticonvulsant concentrations

  1. Is there a prognostic relevance of electrophysiological studies in bundle branch block patients?

    Science.gov (United States)

    Bogossian, Harilaos; Frommeyer, Gerrit; Göbbert, Kornelius; Hasan, Fuad; Nguyen, Quy Suu; Ninios, Ilias; Mijic, Dejan; Bandorski, Dirk; Hoeltgen, Reinhard; Seyfarth, Melchior; Lemke, Bernd; Eckardt, Lars; Zarse, Markus

    2017-08-01

    The present European guidelines suggest a diagnostic electrophysiological (EP) study to determine indication for cardiac pacing in patients with bundle branch block and unexplained syncope. We evaluated the prognostic relevance of an EP study for mortality and the development of permanent complete atrioventricular (AV) block in patients with symptomatic bifascicular block and first-degree AV block. The HV interval is a poor prognostic marker to predict the development of permanent AV block in patients with symptomatic bifascicular block (BFB) and AV block I°. Thirty consecutive patients (mean age, 74.8 ± 8.6 years; 25 males) with symptomatic BFB and first-degree AV block underwent an EP study before device implantation, according to current guidelines. For 53 ± 31 months, patients underwent yearly follow-up screening for syncope or higher-degree AV block. Thirty patients presented with prolonged HV interval during the EP study (mean, 82.2 ± 20.1 ms; range, 57-142 ms), classified into 3 groups: group 1, 70 to ≤100 ms (mean, 80 ± 8 ms; range, 70-97 ms; n = 18), and group 3, >100 ms (mean, 119 ± 14 ms; range, 107-142 ms; n = 5). According to the guidelines, patients in groups 2 and 3 received a pacemaker. The length of the HV interval was not associated with the later development of third-degree AV block or with increased mortality. Our present study suggests that an indication for pacemaker implantation based solely on a diagnostic EP study with prolongation of the HV interval is not justified. © 2017 Wiley Periodicals, Inc.

  2. Wolff-Parkinson-White syndrome type B and left bundle-branch block: electrophysiologic and radionuclide study

    Energy Technology Data Exchange (ETDEWEB)

    Rakovec, P.; Kranjec, I.; Fettich, J.J.; Jakopin, J.; Fidler, V.; Turk, J.

    1985-01-01

    Coinciding left bundle-branch block and Wolff-Parkinson-White syndrome type B, a very rare electrocardiographic occurrence, was found in a patient with dilated cardiomyopathy. Electrophysiologic study revealed eccentric retrograde atrial activation during ventricular pacing, suggesting right-sided accessory pathway. At programmed atrial pacing, effective refractory period of the accessory pathway was 310 ms; at shorter pacing coupling intervals, normal atrioventricular conduction with left bundle-branch block was seen. Left bundle-branch block was seen also with His bundle pacing. Radionuclide phase imaging demonstrated right ventricular phase advance and left ventricular phase delay; both right and left ventricular phase images revealed broad phase distribution histograms. Combined electrophysiologic and radionuclide investigations are useful to disclose complex conduction abnormalities and their mechanical correlates.

  3. Wolff-Parkinson-White syndrome type B and left bundle-branch block: electrophysiologic and radionuclide study

    International Nuclear Information System (INIS)

    Rakovec, P.; Kranjec, I.; Fettich, J.J.; Jakopin, J.; Fidler, V.; Turk, J.

    1985-01-01

    Coinciding left bundle-branch block and Wolff-Parkinson-White syndrome type B, a very rare electrocardiographic occurrence, was found in a patient with dilated cardiomyopathy. Electrophysiologic study revealed eccentric retrograde atrial activation during ventricular pacing, suggesting right-sided accessory pathway. At programmed atrial pacing, effective refractory period of the accessory pathway was 310 ms; at shorter pacing coupling intervals, normal atrioventricular conduction with left bundle-branch block was seen. Left bundle-branch block was seen also with His bundle pacing. Radionuclide phase imaging demonstrated right ventricular phase advance and left ventricular phase delay; both right and left ventricular phase images revealed broad phase distribution histograms. Combined electrophysiologic and radionuclide investigations are useful to disclose complex conduction abnormalities and their mechanical correlates

  4. Use of magnetic resonance to study biodistribution of dextran-coated magnetic fluid intravenously administered in mice

    International Nuclear Information System (INIS)

    Lacava, L.M.; Lacava, Z.G.M.; Azevedo, R.B.; Chaves, S.B.; Garcia, V.A.P.; Silva, O.; Pelegrini, F.; Buske, N.; Gansau, C.; Da Silva, M.F.; Morais, P.C.

    2002-01-01

    Magnetic resonance was used to investigate the kinetic disposition and the subsequent biodistribution of dextran-coated magnetite nanoparticles (9.4 nm core diameter) after intravenous injection of a bolus dose in female Swiss mice. The X-band spectra show a broad single-line at g∼2, typical of nanomagnetic particles suspended in a non-magnetic matrix. In the first 90 min the time-decay of the nanoparticle concentration in the bloodstream follows the one-exponential (one-compartment) model with a half-life of 6.9 min. With respect to blood the clearance (90 μl/min) and the volume of distribution (900 μl) were obtained from the magnetic resonance data. Magnetite nanoparticles were found 90 min after administration in liver and spleen with a typical absorption half-life of 14 min

  5. Electrophysiological effects of desflurane in children with Wolff-Parkinson-White syndrome: a randomized crossover study.

    Science.gov (United States)

    Hino, H; Oda, Y; Yoshida, Y; Suzuki, T; Shimada, M; Nishikawa, K

    2018-02-01

    We hypothesized that, compared with propofol, desflurane prolongs the antegrade accessory pathway effective refractory period (APERP) in children undergoing radiofrequency catheter ablation for Wolff-Parkinson-White (WPW) syndrome. In this randomized crossover study, children aged 4.1-16.1 years undergoing radiofrequency catheter ablation for WPW syndrome were randomly divided into four groups according to the concentration of desflurane and anesthetics used in the first and the second electrophysiological studies (EPS). After induction of general anesthesia with propofol and tracheal intubation, they received one of the following regimens: 0.5 minimum alveolar concentration (MAC) desflurane (first EPS) and propofol (second EPS) (Des0.5-Prop group, n = 8); propofol (first EPS) and 0.5 MAC desflurane (second EPS) (Prop-Des0.5 group, n = 9); 1 MAC desflurane (first EPS) and propofol (second EPS) (Des1.0-Prop group, n = 10); propofol (first EPS) and 1 MAC desflurane (second EPS) (Prop-Des1.0 group, n = 9). Radiofrequency catheter ablation was performed upon completion of EPS. Sample size was determined to detect a difference in the APERP. Desflurane at 1.0 MAC significantly prolonged the APERP compared with propofol, but did not affect the sinoatrial conduction time, atrio-His interval or atrioventricular node effective refractory period. Supraventricular tachycardia was induced in all children receiving propofol, but not induced in 1 and 4 children receiving 0.5 MAC and 1.0 MAC desflurane, respectively. Desflurane enhances the refractoriness and may block the electrical conduction of the atrioventricular accessory pathway, and is therefore not suitable for use in children undergoing radiofrequency catheter ablation for WPW syndrome. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  6. Electrophysiological evaluation of phrenic nerve injury during cardiac surgery – a prospective, controlled, clinical study

    Directory of Open Access Journals (Sweden)

    Ege Turan

    2004-01-01

    Full Text Available Abstract Background According to some reports, left hemidiaphragmatic paralysis due to phrenic nerve injury may occur following cardiac surgery. The purpose of this study was to document the effects on phrenic nerve injury of whole body hypothermia, use of ice-slush around the heart and mammary artery harvesting. Methods Electrophysiology of phrenic nerves was studied bilaterally in 78 subjects before and three weeks after cardiac or peripheral vascular surgery. In 49 patients, coronary artery bypass grafting (CABG and heart valve replacement with moderate hypothermic (mean 28°C cardiopulmonary bypass (CPB were performed. In the other 29, CABG with beating heart was performed, or, in several cases, peripheral vascular surgery with normothermia. Results In all patients, measurements of bilateral phrenic nerve function were within normal limits before surgery. Three weeks after surgery, left phrenic nerve function was absent in five patients in the CPB and hypothermia group (3 in CABG and 2 in valve replacement. No phrenic nerve dysfunction was observed after surgery in the CABG with beating heart (no CPB or the peripheral vascular groups. Except in the five patients with left phrenic nerve paralysis, mean phrenic nerve conduction latency time (ms and amplitude (mV did not differ statistically before and after surgery in either group (p > 0.05. Conclusions Our results indicate that CPB with hypothermia and local ice-slush application around the heart play a role in phrenic nerve injury following cardiac surgery. Furthermore, phrenic nerve injury during cardiac surgery occurred in 10.2 % of our patients (CABG with CPB plus valve surgery.

  7. Confocal microscopy and electrophysiological study of single patient corneal endothelium cell cultures

    Science.gov (United States)

    Tatini, Francesca; Rossi, Francesca; Coppi, Elisabetta; Magni, Giada; Fusco, Irene; Menabuoni, Luca; Pedata, Felicita; Pugliese, Anna Maria; Pini, Roberto

    2016-04-01

    The characterization of the ion channels in corneal endothelial cells and the elucidation of their involvement in corneal pathologies would lead to the identification of new molecular target for pharmacological treatments and to the clarification of corneal physiology. The corneal endothelium is an amitotic cell monolayer with a major role in preserving corneal transparency and in regulating the water and solute flux across the posterior surface of the cornea. Although endothelial cells are non-excitable, they express a range of ion channels, such as voltage-dependent Na+ channels and K+ channels, L-type Ca2 channels and many others. Interestingly, purinergic receptors have been linked to a variety of conditions within the eye but their presence in the endothelium and their role in its pathophysiology is still uncertain. In this study, we were able to extract endothelial cells from single human corneas, thus obtaining primary cultures that represent the peculiarity of each donor. Corneas were from tissues not suitable for transplant in patients. We characterized the endothelial cells by confocal microscopy, both within the intact cornea and in the primary endothelial cells cultures. We also studied the functional role of the purinergic system (adenosine, ATP and their receptors) by means of electrophysiological recordings. The experiments were performed by patch clamp recordings and confocal time-lapse microscopy and our results indicate that the application of purinergic compounds modulates the amplitude of outward currents in the isolated endothelial cells. These findings may lead to the proposal of new therapies for endothelium-related corneal diseases.

  8. Electrophysiological study for comparing the effect of biological activity between type A botulinum toxins in rat gastrocnemius muscle.

    Science.gov (United States)

    Kim, C-S; Jang, W S; Son, I P; Nam, S H; Kim, Y I; Park, K Y; Kim, B J; Kim, M N

    2013-09-01

    New cosmetic applications and products based on the effects of botulinum toxin (BTX) treatment have stimulated demand for this class of natural compounds. This demand generates the need for appropriate standardized protocols to test and compare the effectiveness of new BTX preparations. Based on the previously described electrophysiological methods, we measured and compared the inhibitory effects of two BTX type A (BTX-A) preparations on neuromuscular transmission through split-body test. The effectiveness was evaluated in terms of the compound muscle action potential (CMAP) and conduction velocity after BTX-A injection. We used a split-body method to compare two different BTX-As in the rat. Based on the changes in the CMAP, the two different BTX-As induced paralytic effect on the rat tibialis anterior muscle. However, the two different BTX-A preparations did not differ significantly in effectiveness and did not induce a delay in conduction velocity. The new BTX-A preparation used in this electrophysiological study had similar effect compared with the previously marketed BTX-A.[AQ: Please approve the edits made to the sentence "The new BTX-A preparation…") We propose that a split-body electrophysiological protocol will be useful in establishing the comparative effectiveness of new BTX products.

  9. Biodistribution of radiolabeled lymphocytes

    International Nuclear Information System (INIS)

    Fawwaz, R.A.; Oluwole, S.; Wang, T.S.; Kuromoto, N.; Iga, C.; Hardy, M.A.; Alderson, P.O.

    1985-01-01

    Factors that might affect the biodistribution and clinical utility of radiolabeled lymphocytes were evaluated in experimental animals. Indium-111 (In-111) labeled lymphocytes obtained from peripheral blood, lymph node, or spleen were found in significant amounts in the lymphoid tissues of Lewis rats as early as 3 hours after infusion. A progressive increase in nodal activity with concomitant fall of activity in other organs followed, indicating active recirculation of the lymphocytes. In vitro irradiation of the In-111 labeled lymphocytes resulted in no detectable lymphocyte recirculation and/or reduced localization in lymphoid tissue. Splenectomized animals and those sensitized to an organ allograft before cell infusion showed increased activity in their bone marrow. These results suggest that the source of the injected cells, cell irradiation dose level and host sensitization should be considered when radiolabeled lymphocytes are being prepared for use in clinical diagnosis and therapy

  10. A low-energy x-ray irradiator for electrophysiological studies

    International Nuclear Information System (INIS)

    Schauer, D.A.; Zeman, G.H.; Pellmar, T.C.

    1989-01-01

    A 50 kVp molybdenum target/filter x-ray tube has been installed inside a lead-shielded Faraday cage. High-dose rates of up to 1.54 Gy min -1 (17.4 keV weighted average photons) have been used to conduct local in vitro irradiations of the hippocampal region of guinea pig brains. Electrophysiological recordings of subtle changes in neuronal activity indicate this system is suitable for this application. (author)

  11. Clinical variables in radiotracer biodistributions

    International Nuclear Information System (INIS)

    Lentle, B.C.; Scott, J.R.; Schmidt, R.P.; Noujaim, A.A.

    1981-01-01

    Numerous iatrogenic causes of altered radiotracer biodistributions have been described. Cancer chemotherapy is a particularly potent cause of changed biodistributions while even a trivial matter such as preparing the skin with an iodine containing antiseptic may cause displacement of technetium from its compounds. In the blocking of thyroid uptake of radioiodines, there is good precedent for the manipulation of regional tissue dosimetry. It is possible to go beyond the mere cataloguing of these effects to look creatively at the subject of comparative tissue biodistributions and hence comparative dosimetry. Effects such as the clinical observation of the interference by cis-platinum with the usual biodistribution of radio-gallium suggests that such compounds can be used as probes each to lead to a better understanding of the mechanism of action of the other

  12. Preclinical acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of ["1"8F]fluorocholine in mice

    International Nuclear Information System (INIS)

    Silveira, Marina B.; Ferreira, Soraya M.Z.M.D.; Nascimento, Leonardo T.C.; Costa, Flávia M.; Mendes, Bruno M.; Ferreira, Andrea V.; Malamut, Carlos; Silva, Juliana B.; Mamede, Marcelo

    2016-01-01

    ["1"8F]Fluorocholine (["1"8F]FCH) has been proven to be effective in prostate cancer. Since ["1"8F]FCH is classified as a new radiopharmaceutical in Brazil, preclinical safety and efficacy data are required to support clinical trials and to obtain its approval. The aim of this work was to perform acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of ["1"8F]FCH. The results could support its use in nuclear medicine as an important piece of work for regulatory in Brazil. - Highlights: • Data demonstrated the high quality, safety and effectiveness of ["1"8F]FCH. • ["1"8F]FCH preclinical profile is in accordance with previously published. • Toxicity, distribution, kinetics and radiation dosimetry were well characterized. • The results are important for regulatory issues in Brazil and other countries.

  13. Technetium-99m radiolabeling of a recombinant dermonecrotic protein (recLiD1) from the Loxosceles venom for biodistribution study

    International Nuclear Information System (INIS)

    Valadares, D.; Felicori, L.; Olortegui, C.C.; Simal, C.; Gouvea dos Santos, R.

    2007-01-01

    In the present study the recombinant form (recLiD1) of a dermonecrotic protein present in the Brazilian brown spider Loxosceles intermedia venom was labeled with technetium-99m using stannous chloride and sodium borohydride as reducing agents. 99mTc-recLiD 1 kept its biological activity evoking dermonecrotic activity in rabbits. In vivo biodistribution in mice with the radiolabeled recLiD 1 showed high kidney uptake followed by stomach and liver uptakes. Also, we can see that 20% of toxin remaining in the skin after 120 min and once absorbed, 99mTc-recLiD 1 is rapidly cleared from the blood with long-lasting. We also observed one displacement of 99mTc-recLiD 1 by one monoclonal antibody raised against L. intermedia venom that indicates specific interaction with kidney tissue. (author)

  14. Lyophilization and rehydration of polymer-coated lipid vesicles containing a lipophilic chelator in the presence of sucrose: Labeling with99m Tc and biodistribution studies

    International Nuclear Information System (INIS)

    Szucs, Margaret; Tilcock, Colin

    1995-01-01

    In this paper we describe studies of the effect of lyophilization and rehydration of polymer-coated lipid vesicles bearing a lipophilic surface chelator upon subsequent labeling with technetium-99m and in vivo biodistribution behavior. Unilamellar vesicles of average diameter 100 nm were prepared containing 2 mol% of the lipophilic chelator phosphatidylethanolamine-diethylenetriaminetetraacetic acid (PE-DTTA) and either 0 or 3 mol% of the lipid-polymer conjugate, dipalmitoyl-phosphatidylethanolamine-monomethoxy polyethylene glycol 5000 (PE-MPEG) in 0.9% sodium chloride to which was added varying amounts of sucrose to a final concentration of 100-500 mM. The size of the vesicles in sucrose was determined before lyophilization and after rehydration and the effect of sucrose on the ability to label the vesicles with pertechnetate in the presence of stannous chloride was determined. Biodistribution studies were done in rabbits with vesicles before lyophilization and after rehydration in order to determine whether the rate of clearance from the blood pool was affected by the lyophilization/rehydration procedure. Results demonstrate that vesicles containing PE-DTTA and without PE-MPEG can be lyophilized and rehydrated with no change in average size or size distribution so long as the external sucrose concentration is greater than approx. 250 mM. When PE-MPEG is also present in the membrane the average vesicle size increases from approx. 140 to 200 nm, consistent with vesicle fusion. However, this small change in vesicle size makes no difference to the resulting circulation half-life. In no case does the presence of sucrose on the exterior of the vesicle interfere with technetium labeling of the vesicle surface

  15. Design, synthesis, and evaluation of gadolinium cationic lipids as tools for biodistribution studies of gene delivery complexes.

    Science.gov (United States)

    Leclercq, Francoise; Cohen-Ohana, Mirit; Mignet, Nathalie; Sbarbati, Andrea; Herscovici, Jean; Scherman, Daniel; Byk, Gerardo

    2003-01-01

    Gadolinium-chelating cationic lipids have been synthesized to obtain lipoplexes with MRI contrast properties. These compounds were designed to follow the biodistribution of synthetic DNA for gene delivery by nuclear magnetic resonance imaging. The lipid MCO-I-68 was synthesized, and chelate complexes with gadolinium were formed and characterized in terms of physicochemical and DNA binding properties. The transfection activity of MCO-I-68-Gd/DNA complexes was assayed in vitro on NIH 3T3. Different formulations of the product were tested. When up to 5% of the gadolinium lipid complexes were co-formulated with the cationic lipid RPR120535 used as a reference, the transfection levels were maintained as compared to RPR120535 alone. To date, only a liposomal formulation of a gadolinium-cationic lipid chelate without DNA had been observed using magnetic resonance imaging. In vivo intratumoral administration of MCO-I-68-Gd/DNA lipoplexes to tumor model led to an important increase of the NMR signal. It was demonstrated that the new complexes also acted as transfection carriers when they were formulated from liposomes.

  16. Radiation dose electrophysiology procedures

    International Nuclear Information System (INIS)

    Hernandez-Armas, J.; Rodriguez, A.; Catalan, A.; Hernandez Armas, O.; Luque Japon, L.; Moral, S.; Barroso, L.; Rfuez-Hdez, R.

    2006-01-01

    The aim of this paper has been to measure and analyse some of the parameters which are directly related with the doses given to patients in two electrophysiology procedures: diagnosis and ablation with radiofrequency. 16 patients were considered in this study. 13 them had an ablation with radiofrequency at the Unit of Electrophysiology at the University Hospital of the Canaries, La Laguna., Tenerife. The results of skin doses, in the ablation cases, were higher than 2 Gy (threshold of some deterministic effects). The average value was 1.1 Gy. The personal doses, measured under the lead apron, for physician and nurses were 4 and 3 micro Sievert. These results emphasised the necessity of radiation protection measures in order to reduce, ad much as possible, the doses to patients. (Author)

  17. [Comparative study of the biodistribution of (99m)Tc-HYNIC-Lys3-Bombesin obtained with the EDDA/tricine and NA/tricine as coligands].

    Science.gov (United States)

    Hernández-Cairo, A; Perera-Pintado, A; Prats-Capote, A; Batista-Cuellar, J F; Casacó-Santana, C

    2012-01-01

    The aim of present investigation was to evaluate biodistribution in healthy animals and in tumor models of the radiopharmaceuticals (99m)Tc-EDDA/tricine-HYNIC-Lys3-Bombesin (HYNIC-Lys3-BN) and (99m)Tc-NA/tricine-HYNIC-Lys3-BN. Biodistribution and pharmacokinetics were carried out over 24 hours. To do so, 24 healthy Wistar rats were used and were administered 37.0 ± 0.8 MBq/rat of each radiopharmaceutical. For the tumor model study, 20 CD-1 nude mice were used and prostate tumors (PC3) were implanted in all the mice. Ten days later, tumor volumes were calculated and 40.00 ± 0.04 MBq/mice of each radiopharmaceutical were injected. Both showed high radiochemical purity: 98.08 ± 0.25% for EDDA/tricine product and 95.1 ± 0.3% for the conjugate with NA/tricine. Uptake of the radiopharmaceutical with NA/tricine was significantly higher in organs of the reticulo-endothelial system of healthy Wistar rats during 24h, specifically in the liver and spleen. Both labeled compounds showed no significant differences between their blood elimination half lives. Average of tumor growth was 0.93 ± 0.02 cm(3) and affinity for tumors showed a growing and specific binding of both radiopharmaceuticals, although it was significantly higher for the EDDA/tricine conjugate. This outcome made it possible to corroborate the direct relationship between the density of gastrin releasing peptide and its receptors (GRPr) and the variation of the accumulation of the radiopharmaceuticals in the tumor. Use of EDDA/tricine as coligand is more appropriate than NA/tricine for labeling of HYNIC-Lys3-BN with (99m)Tc. Copyright © 2011 Elsevier España, S.L. y SEMNIM. All rights reserved.

  18. Radiosynthesis of N-¹¹C-Methyl-Taurine-Conjugated Bile Acids and Biodistribution Studies in Pigs by PET/CT.

    Science.gov (United States)

    Schacht, Anna Christina; Sørensen, Michael; Munk, Ole Lajord; Frisch, Kim

    2016-04-01

    During cholestasis, accumulation of conjugated bile acids may occur in the liver and lead to hepatocellular damage. Inspired by our recent development of N-(11)C-methyl-glycocholic acid-that is, (11)C-cholylsarcosine-a tracer for PET of the endogenous glycine conjugate of cholic acid, we report here a radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids and biodistribution studies in pigs by PET/CT. A radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids was developed and used to prepare N-(11)C-methyl-taurine conjugates derived from cholic, chenodeoxycholic, deoxycholic, ursodeoxycholic, and lithocholic acid. The lipophilicity of these new tracers was determined by reversed-phase thin-layer chromatography. The effect of lipophilicity and structure on the biodistribution was investigated in pigs by PET/CT using the tracers derived from cholic acid (3α-OH, 7α-OH, 12α-OH), ursodeoxycholic acid (3α-OH, 7β-OH), and lithocholic acid (3α-OH). The radiosyntheses of the N-(11)C-methyl-taurine-conjugated bile acids proceeded with radiochemical yields of 61% (decay-corrected) or greater and radiochemical purities greater than 99%. PET/CT in pigs revealed that the tracers were rapidly taken up by the liver and secreted into bile. There was no detectable radioactivity in urine. Significant reflux of N-(11)C-methyl-taurolithocholic acid into the stomach was observed. We have successfully developed a radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids. These tracers behave in a manner similar to endogenous taurine-conjugated bile acids in vivo and are thus promising for functional PET of patients with cholestatic diseases. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  19. Clinical variables in radiotracer biodistributions

    International Nuclear Information System (INIS)

    Lentle, B.C.; Scott, J.R.; Schmidt, R.P.; Noujaim, A.A.

    1981-01-01

    Radionuclide dosimetry must, by its nature, define tissue irradiation in terms of mean exposure in a population of a statistically acceptable size. In the daily practice of clinical nuclear medicine there are, however, quite large variations in the biodistribution of tracers and thus in resulting radiation doses. Age is a variable, particularly in respect of bone-seeking tracers. Sex imposes variations in radiation dose on account of the differing anatomical configurations of the gonads. Breast uptake and excretion of certain tracers in women are additional variables. Activity and occupation are occasional variables. Numerous iatrogenic causes of altered radiotracer biodistributions have been described. Cancer chemotherapy is a particularly potent cause of changed biodistributions while even a trivial matter such as preparing the skin with an iodine containing antiseptic may cause displacement of technetium from its compounds. In the blocking of thyroid uptake of radioiodines, there is good precedent for the manipulation of regional tissue dosimetry. It is possible to go beyond the mere cataloguing of these effects to look creatively at the subject of comparative tissue biodistributions and hence comparative dosimetry. Effects such as the clinical observation of the interference by cis-platinum with the usual biodistribution of radio-gallium suggest that such compounds can be used as probes each to lead to a better understanding of the mechanism of action of the other

  20. Estudio electrofisiologico en la neuropatia por Vincristina Vincristine neuropathy: an electrophysiological study

    Directory of Open Access Journals (Sweden)

    Olga P. Sanz

    1975-12-01

    Full Text Available Diez pacientes afectados por diversas patologías que requerían tratamiento crónico con Vincristina, fueron sometidos a estudios electrofisiológicos en los que se valoró: el número de unidades motoras (UM funcionantes en los músculos de la eminencia tenar, los valores de los incrementos medios de UM, velocidad de conducción motora y su latencia residual en el nervio mediano, la velocidad de conducción sensitiva del mismo nervio y el estado de la transmisión neuromuscular. Los valores obtenidos fueron comparados con grupos controles. Los resultados mostraron disminución del número de UM; las UM remanentes presentaron amplitud reducida junto a otras cuyo tamaño no superaba el del grupo control, hecho que sugiere la incapacidad de lograr una reinervación adecuada. Las velocidades de conducción motora y sensitiva mostraron valores diminuídos, con mayor compromiso en los segmentos distales. Junto a estos datos se halló respuesta miasteniforme al estímulo repetitivo. Todos estos resultados permiten postular la existencia de un compromiso de la unidad motora, abarcando todos sus segmentos, en pacientes intoxicados con Vincristina.Ten patients treated with vincristine were submitted for electrophysiological examination. It was investigated the number of motor units within the thenar muscle following a technique described previously (Sica et al. — 1974; motor and sensitive conduction velocities as well as motor distal latencies in the median nerve were studied following conventional techniques. The behaviour of the evoked muscle potential with repetitive supramaximal stimulation over the median nerve was also investigated. The findings were compared with control groups. The estimated number of motor units was disminished in eight of ten patients and the average number was significantly different from the control group (control 318 ± 71 UM; patients 174 ± 84 UM; P < 0.001. The potential amplitudes in most of the surviving units were

  1. Heterogeneity of Monosymptomatic Resting Tremor in a Prospective Study: Clinical Features, Electrophysiological Test, and Dopamine Transporter Positron Emission Tomography.

    Science.gov (United States)

    Zheng, Hua-Guang; Zhang, Rong; Li, Xin; Li, Fang-Fei; Wang, Ya-Chen; Wang, Xue-Mei; Lu, Ling-Long; Feng, Tao

    2015-07-05

    The relationship between monosymptomatic resting tremor (mRT) and Parkinson's disease (PD) remains controversial. In this study, we aimed to assess the function of presynaptic dopaminergic neurons in patients with mRT by dopamine transporter positron emission tomography (DAT-PET) and to evaluate the utility of clinical features or electrophysiological studies in differential diagnosis. Thirty-three consecutive patients with mRT were enrolled prospectively. The Unified Parkinson's Disease Rating Scale and electromyography were tested before DAT-PET. Striatal asymmetry index (SAI) was calculated, and a normal DAT-PET was defined as a SAI of hygiene score, walking in motor experiences of daily living (Part II) and motor examination (Part III) were significant different between two groups (P postural tremor tend to be higher in the SWEDDs group (P = 0.08 and P = 0.05, respectively). mRT is heterogeneous in presynaptic nigrostriatal dopaminergic degeneration, which can be determined by DAT-PET brain imaging. Clinical and electrophysiological features may provide clues to distinguish PD from SWEDDs.

  2. Experimental Studies of Boronophenylalanine ({sup 10}BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Carpano, Marina; Perona, Marina; Rodriguez, Carla [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); Nievas, Susana; Olivera, Maria; Santa Cruz, Gustavo A. [Department of Boron Neutron Capture Therapy, National Atomic Energy Commission, San Martín (Argentina); Brandizzi, Daniel; Cabrini, Romulo [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); School of Dentistry, University of Buenos Aires, Buenos Aires (Argentina); Pisarev, Mario [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); National Research Council of Argentina, Buenos Aires (Argentina); Department of Human Biochemistry, School of Medicine, University of Buenos Aires, Buenos Aires (Argentina); Juvenal, Guillermo Juan [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); National Research Council of Argentina, Buenos Aires (Argentina); Dagrosa, Maria Alejandra, E-mail: dagrosa@cnea.gov.ar [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); National Research Council of Argentina, Buenos Aires (Argentina)

    2015-10-01

    Purpose: Patients with the same histopathologic diagnosis of cutaneous melanoma treated with identical protocols of boron neutron capture therapy (BNCT) have shown different clinical outcomes. The objective of the present studies was to evaluate the biodistribution of boronophenilalanina ({sup 10}BPA) for the potential application of BNCT for the treatment of melanoma on an individual basis. Methods and Materials: The boronophenilalanine (BPA) uptake was evaluated in 3 human melanoma cell lines: MEL-J, A375, and M8. NIH nude mice were implanted with 4 10{sup 6} MEL-J cells, and biodistribution studies of BPA (350 mg/kg intraperitoneally) were performed. Static infrared imaging using a specially modified infrared camera adapted to measure the body infrared radiance of small animals was used. Proliferation marker, Ki-67, and endothelial marker, CD31, were analyzed in tumor samples. Results: The in vitro studies demonstrated different patterns of BPA uptake for each analyzed cell line (P<.001 for MEL-J and A375 vs M8 cells). The in vivo studies showed a maximum average boron concentration of 25.9 ± 2.6 μg/g in tumor, with individual values ranging between 11.7 and 52.0 μg/g of {sup 10}B 2 hours after the injection of BPA. Tumor temperature always decreased as the tumors increased in size, with values ranging between 37°C and 23°C. A significant correlation between tumor temperature and tumor-to-blood boron concentration ratio was found (R{sup 2} = 0.7, rational function fit). The immunohistochemical studies revealed, in tumors with extensive areas of viability, a high number of positive cells for Ki-67, blood vessels of large diameter evidenced by the marker CD31, and a direct logistic correlation between proliferative status and boron concentration difference between tumor and blood (R{sup 2} = 0.81, logistic function fit). Conclusion: We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT

  3. Synthesis and biodistribution study of 3-iodo-4-hydroxyphenyl-cysteamine for detection of malignant melanoma based on specific enzyme of melanin formation

    International Nuclear Information System (INIS)

    Nishii, R.; Nagamachi, S.; Tamura, S.; Kawai, K.; Nishimura, K.; Kinuya, S.; Uehara, T.; Tonami, N.; Arano, Y.

    2002-01-01

    Purpose: The aim of our study is to develop a new radiopharmaceutical labeled with radioiodine for detection and therapy of tumors, which have affinity to a characteristic metabolism in tumor. 3-Iodo-4-hydroxyphenyl-L-cysteine (I- L-PC), which we have reported previously, was found to have an interaction for tyrosinase, an essential and rate-limiting enzyme to melanin biosynthesis. In this study, considering higher affinity for tyrosinase, we synthesized 3-iodo-4-hydroxyphenylcysteamine (I-PCA) that was an amine derivative of I-L-PC and examined biodistribution study in melanoma-bearing mice. Method/Materials: 4-Hydroxyphenylcysteamine (4-PCA) was synthesized and radioiodinated in our laboratory. Synthesis of 4-PCA was confirmed by 1 H-NMR, mass spectrometry and elemental analysis. 125 I-PCA was prepared by conventional chloramine-T method under a no-carrier added condition. 125 I-PCA was purified by Sep-Pak-C-18 cartridge and the labeling efficiency and radiochemical purity were examined by TLC analysis. Biodistribution study of I-PCA was performed using B16 melanoma-bearing C57BL6 mice. The radioactivities of each organ were measured and % injected dose / g wet tissue was determined. Moreover, the tumor-to-blood ratio (T/B ratio) and tumor-to-muscle ratios (T/M ratio) of 125 I-PCA were also evaluated and were compared with 125 I-L-PC, 67 Ga-citrate, 125 I-L-AMT and 123 I-MIBG. Results: Radiosynthesis of 125 I-PCA was carried out conveniently and efficiently within only 15 min. A labeling efficiency of more than 73 % resulted in the labeling of 4-PCA to 125 I-PCA. After the simple Sep-Pak purification, no-carrier added 125 I-PCA with radiochemical purity greater than 90 % was obtained. The biodistribution of 125 I-PCA showed rapid blood clearance, renal excretion and low accumulation in normal tissue, while increase of accumulation in the tumor for 30 min. As a consequence, T/B ratio reached approximately 1.6 ± 0.3 and T/M ratio increased up to 8.7 ± 3.2 at 60

  4. Whole-body biodistribution and brain PET imaging with [{sup 18}F]AV-45, a novel amyloid imaging agent - a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Lin, K.-J. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taiwan (China); Hsu, W.-C. [Department of Neurology, Chang Gung Memorial Hospital, Taiwan (China); Hsiao, I.-T.; Wey, S.-P. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taiwan (China); Jin, L.-W. [M.I.N.D. Institute and Department of Pathology, University of California, Davis, CA (United States); Skovronsky, Daniel [Avid Radiopharmaceuticals, Inc., Philadelphia, PA (United States); Wai, Y.-Y. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Radiology, Chang Gung Memorial Hospital, Taiwan (China); Chang, H.-P.; Lo, C.-W.; Yao, C.H.; Yen, T.-C. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Kung, M.-P. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Radiology, University of Pennsylvania, Philadelphia, PA (United States)

    2010-05-15

    Purpose: The compound (E)-4-(2-(6-(2-(2-(2-{sup 18}F-fluoroethoxy)ethoxy)ethoxy) pyridin-3-yl)vinyl)-N-methylbenzenamine ([{sup 18}F]AV-45) is a novel radiopharmaceutical capable of selectively binding to {beta}-amyloid (A{beta}) plaques. This pilot study reports the safety, biodistribution, and radiation dosimetry of [{sup 18}F]AV-45 in human subjects. Methods: In vitro autoradiography and fluorescent staining of postmortem brain tissue from patients with Alzheimer's disease (AD) and cognitively healthy subjects were performed to assess the specificity of the tracer. Biodistribution was assessed in three healthy elderly subjects (mean age: 60.0{+-}5.2 years) who underwent 3-h whole-body positron emission tomography (PET)/computed tomographic (CT) scans after a bolus injection of 381.9{+-}13.9 MBq of [{sup 18}F]AV-45. Another six subjects (three AD patients and three healthy controls, mean age: 67.7{+-}13.6 years) underwent brain PET studies. Source organs were delineated on PET/CT. All subjects underwent magnetic resonance imaging (MRI) for obtaining structural information. Results: In vitro autoradiography revealed exquisitely high specific binding of [{sup 18}F]AV-45 to postmortem AD brain sections, but not to the control sections. There were no serious adverse events throughout the study period. The peak uptake of the tracer in the brain was 5.12{+-}0.41% of the injected dose. The highest absorbed organ dose was to the gallbladder wall (184.7{+-}78.6 {mu}Gy/MBq, 4.8 h voiding interval). The effective dose equivalent and effective dose values for [{sup 18}F]AV-45 were 33.8{+-}3.4 {mu}Sv/MBq and 19.3{+-}1.3 {mu}Sv/MBq, respectively. Conclusion: [{sup 18}F]AV-45 binds specifically to A{beta} in vitro, and is a safe PET tracer for studying A{beta} distribution in human brain. The dosimetry is suitable for clinical and research application.

  5. Exploration of dopamine transporter and D2 receptors in morphine dependent rats through 125I-β-CTT, 125I-IBZM cerebral autoradiography and the biodistribution study

    International Nuclear Information System (INIS)

    Lin Yansong; Fang Ping; Ding Shiyu; Chen Zhengping; Zhou Xiang; Hu Mingyang; Wang Bocheng; Zhang Manda; Wang Shizhen

    2001-01-01

    Objective: To explore the variation of cerebral dopamine (DA) transmitting system in morphine dependent (MD) rats using dopamine transporter (DAT) and D 2 receptors imaging agent. Methods: MD model rats were established by using a two-compartment (C1 and C2-morphine conditioned compartment) apparatus for assessing morphine conditioned place preferences in rats. 125 I-2β-carbomethoxy-3β-(4-iodophenyl) tropane ( 125 I-β-CIT) and 125 I-3-iodo-2-hydroxy-6-methoxy-N[(1-ethyl-2-pyrrolidinyl) methyl] benzamide ( 125 I-IBZM) cerebral DAT and D 2 receptor autoradiography and biodistribution study were used to evaluate the variation of DAT and D 2 receptors in morphine dependent rats. Results: The mean time of MD rats entering from C1 to C2 was (0.84 +- 0.50) min after 6 days' conditioned place preference training, shorter than that of the control group [(2.40 +- 1.10) min, P 125 I-β-CIT uptake ratio of striatum (ST)/cerebellum (CB) and nucleus acumens (NAC)/CB in MD group were 4.76 +- 0.92 and 2.72 +- 0.96, significantly lower than that of control group (5.92 +- 0.67 and 4.16 +- 0.56, P 125 I-IBZM uptake ratio in MD group were 4.11 +- 0.56 and 2.64 +- 0.25, lower than that in control group (5.43 +- 0.74 and 3.49 +- 0.65, P 125 I-β-CIT, 125 I-IBZM biodistribution study also showed that the DAT and D 2 binding sites were reduced in ST of MD group by (21.68 +- 11.11)% and (18.69 +- 9.97)% comparing to the controls, respectively. Conclusions: The DAT and D 2 receptors in both ST and NAC were all involved and reduced to some extent in morphine dependent model rats, the DAT and D 2 receptor imaging agent could reflect the variation of DAT and D 2 receptors, this would afford the theoretical basis for D 2 receptors and DAT imaging in study on preventing drug addiction and on its abstinence

  6. Biodistribution, pharmacokinetic, and imaging studies with 186Re-labeled NR-LU-10 whole antibody in LS174T colonic tumor-bearing mice

    International Nuclear Information System (INIS)

    Goldrosen, M.H.; Biddle, W.C.; Pancook, J.; Bakshi, S.; Vanderheyden, J.L.; Fritzberg, A.R.; Morgan, A.C. Jr.; Foon, K.A.

    1990-01-01

    Biodistribution, pharmacokinetic, and radioimaging studies were performed with 186Re-labeled NR-LU-10 whole antibody in athymic nude mice bearing the LS174T tumor growing either s.c. or in an experimental hepatic metastasis model. NR-LU-10 is an IgG2b murine monoclonal antibody (MAb) that reacts with virtually all human tumors of epithelial origin. NR-BC-1, a IgG2b murine MAb that reacts with normal human B-cell and B malignancies, was used as an isotype-matched control. These MAbs were radiolabeled with 186Re by a preformed chelate approach by using the triamide thiolate ligand system. 186Re-labeled NR-LU-10 (50 microCi) was injected into nude mice bearing LS174T tumors growing s.c. Biodistribution studies revealed that the LS174T tumor retained the highest concentration of 186Re-labeled NR-LU-10 at day 6. The tumor:blood ratio ranged from 0.1:1 to 10.8:1 by day 6, the last day of analysis. In contrast the tumor:blood ratio of 186Re-labeled NR-BC-1, the isotype-matched MAb control, was 1:1 on day 6. Pharmacokinetic analysis indicated that the t1/2 beta of NR-LU-10 for blood and other tissues ranged from 21 to 25 h, while the t1/2 beta for the LS174T tumor averaged 52 h. The area under the curve for tumor compared to blood was 2.8- to 5.7-fold higher than the area under the curve for all other tissues and organs. The mean residence time for NR-LU-10 in blood and all other organs ranged from 23 to 26 h, while the mean residence time for NR-LU-10 in the LS174T tumor was 72 h. Scintigraphic images revealed selective uptake of the 186Re-labeled NR-LU-10, but not of the 186Re-labeled NR-BC-1, at the LS174T tumor site. Studies in an experimental model of hepatic metastasis revealed a similar selective pattern of 186Re-labeled NR-LU-10 accumulation. Scintigraphic images of the LS174T tumor growing within the athymic nude mouse liver were obtained

  7. The experimental study on biodistribution and radioimmunoimaging of 131I labeled anti-lymphoma Fab antibody in nude mice bearing human B cell lymphoma

    International Nuclear Information System (INIS)

    Yang Xiaochun; Zhang Meihua; Shen Junkang; Shen Yongmei; Shi Yizhen; Liu Zengli

    2008-01-01

    Objective: Radioimmunoimaging is still an interesting study in the domain of nuclear medicine. The aim of this study was to evaluate the biodistribution and radioimmunoimaging of 131 I-Fab anti- body in nude mice beating human B cell lymphoma. Methods: The immunoreactivity of Fab antibody to Raji cells was analyzed by immunohistochemistry and flow cytometry. Fab antibody and CD20 monoclonal antibody (as control) were labeled with 131 I using Iodogen method. 131 I-Fab antibody or 131 I-CD20 was injected into nude mice bearing B cell lymphoma via tail veins. The biodistribution and radioimmunoimaging results were obtained at 2, 4, 8 and 24 h postinjection, respectively. Results: The results of immunohistochemistry and flow cytometry indicated that both Fab antibody and 131 I-Fab antibody could bind strongly with membrane antigens on Raji cells, and the binding rate reached above 87%. Clear tumor image was obtained at 8 h after injection with 131 I-Fab and elimination was observed at 24 h postinjection. The clear tumor image for 131 I-CD20 antibody was obtained at 24 h post injection. The biodistribution in vivo showed that the percentage activities of injection dose per gram of tumor (% ID/g) of 131 I-Fab group at 2, 4, 8 h postinjection were higher than that of 131 I-CD20 antibody [(1.37±0.28), (1.84±0.13), (2.21±0.15)% ID/g vs (0.33±0.06), (0.62±0.08), (1.46±0.24)% ID/g, respectively; F=52.22, 278.42 and 29.00, all P 131 I-Fad and 131 I-CD20 groups at 2, 4, 8 and 24 h were [(0.22±0.03)-(5.44± 0.31)] vs[(0.04±0.01)-(3.10±0.29)], [(0.43±0.11) - (21.01±3.97)] vs [(0.11±0.05) - (7.99±1.81)], [(1.09±0.07) -(20.28±2.77)] vs [(0.48±0.06) - (23.55±1.69)], [(1.12± 0.02) - (10.29±1.78)] vs [(2.32 ± 0.34) - (33.23±6.83)], respectively. Conclusion: 131 I-Fab anti- body has advantages of small molecular weight, excellent targeting characteristics, early imaging and fast elimination, which indicates the potential application value in diagnosing B cell

  8. Preparation and standardization of an 'in vitro' labeling methodology and study of [99mTc]-EDDA/tricine/HYNIC-[Tyr3]-octreotide biodistribution

    International Nuclear Information System (INIS)

    Hernandes Melero, Laura Terumi Ueda

    2008-01-01

    -HYNIC, 10 mg of EDDA, 20 mg of tricine, 150 g of Sn C 12 .2H 2 O in a final pH 8.0, and activity up to 3700 MBq (100 mCi). This formulation can be an alternative for the administration of more than one patient per labeling procedure, using a lyophilized reagent. The biodistribution performed by invasive method in the intervals of 1.5 and 4 hours after intravenous administration of the radiopharmaceutical in Swiss mice determined the percentage of the activity administered in the blood and the various organs. The biodistribution data in Swiss and Nude mice bearing AR42J tumor (rat pancreatic adenocarcinoma) were compatible with the distribution of the labeled peptide: fast blood clearance, high uptake in the kidneys due to the elimination by the urinary tract, and high uptake in organs with high density of somatostatin receptors like lung, stomach, pancreas and tumor in the case of Nude mice. The uptake of the radiolabeled peptide in the abdominal region was not significant and represents an advantage related to the diagnosis of neuroendocrine tumors, frequently found in this region. The labeling and biodistribution results described in this study showed the potential of the 99m Tc-labeled peptide to be applied in diagnostic procedures in nuclear medicine. (author)

  9. Preparation and standardization of an 'in vitro' labelling methodology and study of [99m Tc]-EDDA/Tricine/Hynic-[Tyr3]-octreotide biodistribution

    International Nuclear Information System (INIS)

    Hernandes Melero, Laura Terumi Ueda

    2008-01-01

    g octreotide-HYNIC, 10 mg of EDDA, 20 mg of tricine, 150 μg of SnCI 2 .2H 2 0 in a final pH 8.0, and activity up to 3700 MBq (100 mCi). This formulation can be an alternative for the administration of more than one patient per labeling procedure, using a lyophilized reagent. The biodistribution performed by invasive method in the intervals of 1.5 and 4 hours after intravenous administration of the radiopharmaceutical in Swiss mice determined the percentage of the activity administered in the blood and the various organs. The biodistribution data in Swiss and Nude mice bearing AR42J tumor (rat pancreatic adenocarcinoma) were compatible with the distribution of the labeled peptide: fast blood clearance, high uptake in the kidneys due to the elimination by the urinary tract, and high uptake in organs with high density of somatostatin receptors like lung, stomach, pancreas and tumor in the case of Nude mice. The uptake of the radiolabeled peptide in the abdominal region was not significant and represents an advantage related to the diagnosis of neuroendocrine tumors, frequently found in this region. The labeling and biodistribution results described in this study showed the potential of the 99m Tc-labeled peptide to be applied in diagnostic procedures in nuclear medicine. (author)

  10. A study of the uptake and biodistribution of nano-titanium dioxide using in vitro and in vivo models of oral intake

    Energy Technology Data Exchange (ETDEWEB)

    MacNicoll, Alan; Kelly, Mick [The Food and Environment Research Agency (United Kingdom); Aksoy, Hatice [TÜBİTAK Marmara Research Center, Food Institute (Turkey); Kramer, Evelien; Bouwmeester, Hans [RIKILT - Institute of Food Safety (Netherlands); Chaudhry, Qasim, E-mail: qasim.chaudhry@fera.gsi.gov.uk [The Food and Environment Research Agency (United Kingdom)

    2015-02-15

    Certain food additives may contain a sizeable fraction of particles in the nanoscale. However, little is known about the fate, behaviour and toxicological effects of orally-ingested nanoparticles. This study investigated the uptake and biodistribution of nano- and larger-sized titanium dioxide (TiO{sub 2}) using an in vitro model of gut epithelium and in vivo in rat. The results of the in vivo study showed that oral administration of 5 mg/kg body weight of TiO{sub 2} nano- or larger particles did not lead to any significant translocation of TiO{sub 2} (measured as titanium) either to blood, urine or to various organs in rat at any of the time intervals studied over a 96 h post-administration period. Different methods used for dispersing particles did not affect the uptake, and orally administered TiO{sub 2} was found excreted in the faeces over a period of time. The in vitro study provided further evidence for the lack of translocation of TiO{sub 2} across the gut epithelium model. The overall evidence from both in vivo and in vitro studies did not support that oral ingestion of nano- or larger particles of TiO{sub 2} via food would result in any significant internal exposure of the consumer to the nanoparticles. The dietary TiO{sub 2} nanoparticles are likely to be excreted in the faeces.

  11. A study of the uptake and biodistribution of nano-titanium dioxide using in vitro and in vivo models of oral intake

    Science.gov (United States)

    MacNicoll, Alan; Kelly, Mick; Aksoy, Hatice; Kramer, Evelien; Bouwmeester, Hans; Chaudhry, Qasim

    2015-02-01

    Certain food additives may contain a sizeable fraction of particles in the nanoscale. However, little is known about the fate, behaviour and toxicological effects of orally-ingested nanoparticles. This study investigated the uptake and biodistribution of nano- and larger-sized titanium dioxide (TiO2) using an in vitro model of gut epithelium and in vivo in rat. The results of the in vivo study showed that oral administration of 5 mg/kg body weight of TiO2 nano- or larger particles did not lead to any significant translocation of TiO2 (measured as titanium) either to blood, urine or to various organs in rat at any of the time intervals studied over a 96 h post-administration period. Different methods used for dispersing particles did not affect the uptake, and orally administered TiO2 was found excreted in the faeces over a period of time. The in vitro study provided further evidence for the lack of translocation of TiO2 across the gut epithelium model. The overall evidence from both in vivo and in vitro studies did not support that oral ingestion of nano- or larger particles of TiO2 via food would result in any significant internal exposure of the consumer to the nanoparticles. The dietary TiO2 nanoparticles are likely to be excreted in the faeces.

  12. A study of the uptake and biodistribution of nano-titanium dioxide using in vitro and in vivo models of oral intake

    International Nuclear Information System (INIS)

    MacNicoll, Alan; Kelly, Mick; Aksoy, Hatice; Kramer, Evelien; Bouwmeester, Hans; Chaudhry, Qasim

    2015-01-01

    Certain food additives may contain a sizeable fraction of particles in the nanoscale. However, little is known about the fate, behaviour and toxicological effects of orally-ingested nanoparticles. This study investigated the uptake and biodistribution of nano- and larger-sized titanium dioxide (TiO 2 ) using an in vitro model of gut epithelium and in vivo in rat. The results of the in vivo study showed that oral administration of 5 mg/kg body weight of TiO 2 nano- or larger particles did not lead to any significant translocation of TiO 2 (measured as titanium) either to blood, urine or to various organs in rat at any of the time intervals studied over a 96 h post-administration period. Different methods used for dispersing particles did not affect the uptake, and orally administered TiO 2 was found excreted in the faeces over a period of time. The in vitro study provided further evidence for the lack of translocation of TiO 2 across the gut epithelium model. The overall evidence from both in vivo and in vitro studies did not support that oral ingestion of nano- or larger particles of TiO 2 via food would result in any significant internal exposure of the consumer to the nanoparticles. The dietary TiO 2 nanoparticles are likely to be excreted in the faeces

  13. Preclinical safety, toxicology, and biodistribution study of adenoviral gene therapy with sVEGFR-2 and sVEGFR-3 combined with chemotherapy for ovarian cancer.

    Science.gov (United States)

    Tuppurainen, Laura; Sallinen, Hanna; Kokki, Emmi; Koponen, Jonna; Anttila, Maarit; Pulkkinen, Kati; Heikura, Tommi; Toivanen, Pyry; Hämäläinen, Kirsi; Kosma, Veli-Matti; Heinonen, Seppo; Alitalo, Kari; Ylä-Herttuala, Seppo

    2013-03-01

    Abstract Antiangiogenic and antilymphangiogenic gene therapy with soluble vascular endothelial growth factor receptor-2 (VEGFR-2) and soluble VEGFR-3 in combination with chemotherapy is a potential new treatment for ovarian carcinoma. We evaluated the safety, toxicology, and biodistribution of intravenous AdsVEGFR-2 and AdsVEGFR-3 combined with chemotherapy in healthy rats (n=90) before entering a clinical setting. The study groups were: AdLacZ and AdLacZ with chemotherapy as control groups, low dose AdsVEGFR-2 and AdsVEGFR-3, high dose AdsVEGFR-2 and AdsVEGFR-3, combination of low dose AdsVEGFR-2 and AdsVEGFR-3 with chemotherapy, combination of high dose AdsVEGFR-2 and AdVEGFR-3 with chemotherapy, and chemotherapy only. The follow-up time was 4 weeks. Safety and toxicology were assessed by monitoring the clinical status of the animals and by histological, hematological, and clinical chemistry parameters. For the biodistribution studies, quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used. Low dose (2×10(10) vp) AdsVEGFR-2 and AdsVEGFR-3 gene therapy was well tolerated, even when gene therapy was combined with chemotherapy. Notably, only transient elevation of liver enzymes and mild regenerative changes were seen in liver after the gene transfer in the groups that received high doses (2×10(11) vp) of AdsVEGFR-2 and AdsVEGFR-3 with or without chemotherapy. No life-threatening adverse effects were noticed in any of the treatment groups. The highest protein concentration of soluble VEGFR-2 (sVEGFR-2) in circulation was seen 1 week after the gene transfer. The combination of chemotherapy to gene therapy seemed to prolong the time of detectable transgene protein at least 1 week in the circulation. The expression of AdsVEGFR-2 and AdsVEGFR-3 transgenes was mainly seen in the liver and spleen as detected by qRT-PCR. According to these results, AdsVEGFR-2 and AdsVEGFR-3 gene therapy combined with

  14. Preparation and biodistribution in mice of ( sup 11 C)carfentanil; A radiopharmaceutical for studying brain. mu. -opioid receptors by positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Saji, Hideo; Tsutsumi, Daisuke; Iida, Yasuhiko; Yokoyama, Akira (Kyoto Univ. (Japan). Faculty of Pharmaceutical Science); Magata, Yasuhiro; Konishi, Junji

    1992-02-01

    A potent {mu}-opioid agonist, ({sup 11}C)carfentanil, was prepared by the methylation of carfentanil carboxylic acid with ({sup 11}C)methyl iodide in order to study brain {mu}-opioid receptors by positron emission tomography. Synthesis (including purification) was completed within 25 min and the radiochemical yield was approximately 40%. The radiochemical purity of the product was more than 99% and its specific activity was 3.7-7.4 GBq/{mu}mol. Biodistribution studies performed in mice after intravenous injection showed a high brain uptake and rapid blood clearance, so a high brain/blood ratio of 1.5-1.8 was found from 5 to 30 min. Regional cerebral distribution studies in the mouse showed a significantly higher uptake of ({sup 11}C)carfentanil by the thalamus and striatum than by the cerebellum, with the radioactivity in the striatum disappearing more rapidly than that in the thalamus. Treatment with naloxone significantly reduced the uptake of ({sup 11}C)carfentanil by the thalamus and striatum. These results indicate that ({sup 11}C)carfentanil binds specifically to brain {mu}-opioid receptors. (author).

  15. In vivo anti-psoriatic activity, biodistribution, sub-acute and sub-chronic toxicity studies of orally administered methotrexate loaded chitin nanogel in comparison with methotrexate tablet.

    Science.gov (United States)

    Panonnummal, Rajitha; Jayakumar, R; Anjaneyan, Gopikrishnan; Sabitha, M

    2018-04-15

    The anti-psoriatic efficacy of orally administered methotrexate loaded chitin nanogel (MCNG) was evaluated (two doses- 2.715 mg/kg and 5.143 mg/kg) and compared against orally administered methotrexate tablet MTX (5.143 mg/kg). MCNG at both dose levels of 2.715 mg/kg and 5.143 mg/kg exhibited significant anti-psoriatic activity which is very much comparable with MTX, caused normalization of histological features and inflammatory score associated with induced psoriasis. Biodistribution studies revealed the presence of drug in serum and in vital organs at all the three cases with highest amount in MCNG at 5.143 mg/kg dose, followed by MTX tablet and are lowest in MCNG at 2.715 mg/kg dose. MCNG at the highest dose of 5.143 mg/kg caused liver, lung and kidney toxicities on sub acute toxicity studies and MTX tablet was found to be toxic on liver and lung on sub chronic toxicity studies. MCNG 2.715 mg/kg was found to be safe on both sub acute and sub chronic administrations, suggesting that it can provide sufficient serum and tissue level of methotrexate necessary to clear psoriatic lesions, without inducing systemic toxicity and expected to be a better alternative for orally administered conventional methotrexate tablet for patients who need systemic medications for psoriasis. Copyright © 2018. Published by Elsevier B.V.

  16. Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies.

    Science.gov (United States)

    Nour, Samia A; Abdelmalak, Nevine S; Naguib, Marianne J; Rashed, Hassan M; Ibrahim, Ahmed B

    2016-11-01

    Clonazepam (CZ) is an anti-epileptic drug used mainly in status epilepticus (SE). The drug belongs to Class II according to BCS classification with very limited solubility and high permeability and it suffers from extensive first-pass metabolism. The aim of the present study was to develop CZ-loaded polymeric micelles (PM) for direct brain delivery allowing immediate control of SE. PM were prepared via thin film hydration (TFH) technique adopting a central composite face-centered design (CCFD). The seventeen developed formulae were evaluated in terms of entrapment efficiency (EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and in vitro release. For evaluating the in vivo behavior of the optimized formula, both biodistrbution using 99m Tc-radiolabeled CZ and pharmacodynamics studies were done in addition to ex vivo cytotoxicty. At a drug:Pluronic® P123:Pluronic® L121 ratio of 1:20:20 (PM7), a high EE, ZP, Q8h, and a low PDI was achieved. The biodistribution studies revealed that the optimized formula had significantly higher drug targeting efficiency (DTE = 242.3%), drug targeting index (DTI = 144.25), and nose-to-brain direct transport percentage (DTP = 99.30%) and a significant prolongation of protection from seizures in comparison to the intranasally administered solution with minor histopathological changes. The declared results reveal the ability of the developed PM to be a strong potential candidate for the emergency treatment of SE.

  17. Iodine-123 labelled nor-{beta}-CIT binds to the serotonin transporter in vivo as assessed by biodistribution studies in rats

    Energy Technology Data Exchange (ETDEWEB)

    Booij, J.; Knol, R.J.J.; Reneman, L.; De Bruin, K.; Van Royen, E.A. [Dept. of Nuclear Medicine, Univ. of Amsterdam (Netherlands); Janssen, A.G.M. [Amersham Cygne and Eindhoven University of Technology (Netherlands)

    1998-12-01

    Iodine-123 labelled 2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)nortropane (nor-{beta}-CIT), a radioiodinated cocaine analogue, was evaluated as an agent for the in vivo labelling of serotonin transporters by biodistribution studies in rats. Intravenous injection of [{sup 123}I]nor-{beta}-CIT resulted in high accumulation of radioactivity in brain areas with high densities of serotonin (hypothalamus) and dopamine transporters (striatum), although the binding was less pronounced in the hypothalamus. While binding of [{sup 123}I]nor-{beta}-CIT in the hypothalamus was blocked significantly by fluvoxamine (a selective serotonin transporter blocker) but not by GBR12,909 (a selective dopamine transporter blocker), the opposite was observed in the striatum. The results of this study indicate that [{sup 123}I]nor-{beta}-CIT, although not being a selective radioligand, binds specifically to serotonin transporters in the hypothalamus in vivo and thus suggest that [{sup 123}I]nor-{beta}-CIT promises to be a suitable radioligand for single-photon emission tomography imaging of serotonin transporters in humans. (orig.) With 1 fig., 2 tabs., 15 refs.

  18. N-[11C]methyl-3,4-methylenedioxyamphetamine (Ecstasy) and 2-methyl-N-[11C]methyl-4,5-methylenedioxyamphetamine. Synthesis and biodistribution studies

    International Nuclear Information System (INIS)

    Patt, M.; Machulla, H.J.; Guendisch, D.; Kovar, K.A.; Wuellner, U.; Blocher, A.

    1999-01-01

    In order to evaluate the neurobiological mechanism causing the psychogenic effects of methylenedioxy-derivatives of amphetamine, the carbon-11 labeled analogues of 3,4-methylenedioxymethamphetamine (MDMA), 2 and 2,N-dimethyl-4,5-methylenedioxyamphetamine (MADAM-6) 4 were prepared for application in in-vivo PET studies by methylation of 3,4-methylenedioxyamphetamine (MDA) 1 and 2-methyl-4,5-methylenedioxyamphetamine 3 with [ 11 C]CH 3 I. The radiochemical yield was determined in dependence on time, temperature and amount of precursor. The best conditions for a fast labeling reaction with carbon-11 on a preparative scale were found to be a reaction time of 10 min using 1 mg of the corresponding dimethyl-precursors 1 or 3, thus obtaining radiochemical yields of 60% (based on produced [ 11 C]CH 3 I). Biodistribution studies were performed in rats, a high brain to blood ratio of 7.5 was observed for [ 11 C]MDMA in contrast to a ratio of 3.7 for [ 11 C]MADAM-6. (author)

  19. Iodine-123 labelled nor-β-CIT binds to the serotonin transporter in vivo as assessed by biodistribution studies in rats

    International Nuclear Information System (INIS)

    Booij, J.; Knol, R.J.J.; Reneman, L.; De Bruin, K.; Van Royen, E.A.; Janssen, A.G.M.

    1998-01-01

    Iodine-123 labelled 2β-carbomethoxy-3β-(4-iodophenyl)nortropane (nor-β-CIT), a radioiodinated cocaine analogue, was evaluated as an agent for the in vivo labelling of serotonin transporters by biodistribution studies in rats. Intravenous injection of [ 123 I]nor-β-CIT resulted in high accumulation of radioactivity in brain areas with high densities of serotonin (hypothalamus) and dopamine transporters (striatum), although the binding was less pronounced in the hypothalamus. While binding of [ 123 I]nor-β-CIT in the hypothalamus was blocked significantly by fluvoxamine (a selective serotonin transporter blocker) but not by GBR12,909 (a selective dopamine transporter blocker), the opposite was observed in the striatum. The results of this study indicate that [ 123 I]nor-β-CIT, although not being a selective radioligand, binds specifically to serotonin transporters in the hypothalamus in vivo and thus suggest that [ 123 I]nor-β-CIT promises to be a suitable radioligand for single-photon emission tomography imaging of serotonin transporters in humans. (orig.)

  20. Toxicology and Biodistribution Studies for MGH2.1, an Oncolytic Virus that Expresses Two Prodrug-activating Genes, in Combination with Prodrugs

    Directory of Open Access Journals (Sweden)

    Kazue Kasai

    2013-01-01

    Full Text Available MGH2.1 is a herpes simplex virus type 1 (HSV1 oncolytic virus that expresses two prodrug-activating transgenes: the cyclophosphamide (CPA-activating cytochrome P4502B1 (CYP2B1 and the CPT11-activating secreted human intestinal carboxylesterase (shiCE. Toxicology and biodistribution of MGH2.1 in the presence/absence of prodrugs was evaluated in mice. MGH2.1 ± prodrugs was cytotoxic to human glioma cells, but not to normal cells. Pharmacokinetically, intracranial MGH2.1 did not significantly alter the metabolism of intraperitoneally (i.p. administered prodrugs in mouse plasma, brain, or liver. MGH2.1 did not induce an acute inflammatory reaction. MGH2.1 DNA was detected in brains of mice inoculated with 108 pfus for up to 60 days. However, only one animal showed evidence of viral gene expression at this time. Expression of virally encoded genes was restricted to brain. Intracranial inoculation of MGH2.1 did not induce lethality at 108 pfus in the absence of prodrugs and at 106 pfus in the presence of prodrugs. This study provides safety and toxicology data justifying a possible clinical trial of intratumoral injection of MGH2.1 with peripheral administration of CPA and/or CPT11 prodrugs in humans with malignant gliomas.

  1. Biodistribution Study of the Anaesthetic Sodium Phenobarbital Labelled with Technetium-99m in Swiss Mice Infected with Schistosoma mansoni Sambon, 1907

    Directory of Open Access Journals (Sweden)

    Susana Balmant Emerique Simões

    1997-09-01

    Full Text Available Technetium-99m (99mTc is a radionuclide that has negligible enviromnental impact, is easily available, inexpensive and can be used as a radioactive tracer in biological experiences. In order to know the mode of action of sodium phenobarbital in moving adult Schistosoma mansoni worms from mesenteric veins to the liver, we labelled sodium phenobarbital (PBBT with 99mTc and a biodistribution study in infected and non-infected Swiss mice was performed. The PBBT was incubated with stannous chloride used as reducing agent and with 99mTc, as sodium pertechnetate. The radioactivity labelling (% was determined by paper ascending chromatography perfomed with acetone (solvent. The 99mTc-PBBT was administered by intraperitoneal route to Swiss mice infected eight weeks before. The animals were perfused after diferent periods of time (0,1,2,3,4 hr when blood, spleen, liver, portal vein, mesenteric veins, stomach, kidneys and adult worms were isolated. The radioactivity present in these samples was counted in a well counter and the percentage was determined. The radioactivity was mainly taken up by the blood, kidney, liver and spleen. No radioactivity was found on the adult worms. We concluded that the worm shift was due to an action on the host of the sodium phenobarbital

  2. Electrophysiological and biochemical studies of slow responses to serotonin and dopamine of snail identified neurons. Mediating role of the cyclic AMP

    International Nuclear Information System (INIS)

    Deterre, Philippe

    1983-01-01

    In this research thesis, the electrophysiological study of slow incoming currents induced in some identified neurons of the Helix aspersa snail by serotonin and dopamine shows that they are associated with a decrease of a potassium conductance involved in the modulation of the action potential duration. By means of enzymatic tests performed on a single cell, and of electrophysiological experiments, the author shows that the cyclic AMP is an intracellular mediator involved in the genesis of these slow responses. Moreover, the obtained results show that serotonin and dopamine act by binding to specific receptors, and that these receptors activate the adenylate-cyclase through a GTP binding protein [fr

  3. Vdrive Evaluation of Remote Steering and Testing in Lasso Electrophysiology Procedures Study: The VERSATILE Study in Atrial Fibrillation Ablation.

    Science.gov (United States)

    Nölker, Georg; Schwagten, Bruno; Deville, J Brian; Burkhardt, J David; Horton, Rodney P; Sha, Qun; Tomassoni, Gery

    2016-03-01

    Circular mapping catheters (CMC) are an essential tool in most atrial fibrillation ablation procedures. The Vdrive™ with V-Loop™ system enables a physician to remotely manipulate a CMC during electrophysiology studies. Our aim was to compare the clinical performance of the system to conventional CMC navigation according to efficiency and safety endpoints. A total of 120 patients scheduled to undergo a CMC study followed by pulmonary vein isolation (PVI) were included. Treatment allocation was randomized 2:1, remote navigation:manual navigation. The primary effectiveness endpoint was assessed based on both successful navigation to the targeted pulmonary vein (PV) and successful recording of PV electrograms. All PVs were treated independently within and between patients. The primary safety endpoint was assessed based on the occurrence of major adverse events (MAEs) through seven days after the study procedure. Primary effectiveness endpoints were achieved in 295/302 PVs in the Vdrive arm (97.7%) and 167/167 PVs in the manual arm (100%). Effectiveness analysis indicates Vdrive non-inferiority (pnon-inferiority = 0.0405; δ = -0.05) per the Cochran-Mantel-Haenszel test adjusted for PV correlation. Five MAEs related to the ablation procedure occurred (three in the Vdrive arm-3.9%; two in the manual arm-2.33%). No device-related MAEs were observed; safety analysis indicates Vdrive non-inferiority (pnon-inferiority = 0.0441; δ = 0.07) per the normal Z test. Remote navigation of a CMC is equivalent to manual in PVI in terms of safety and effectiveness. This allows for single-operator procedures in conjunction with a magnetically guided ablation catheter. © 2016 Wiley Periodicals, Inc.

  4. Electrophysiologic studies of cutaneous nerves of the forelimb of the cat.

    Science.gov (United States)

    Kitchell, R L; Canton, D D; Johnson, R D; Maxwell, S A

    1982-10-01

    The cutaneous innervation of the forelimb was investigated in 20 barbiturate-anesthetized cats by using electrophysiological techniques. The cutaneous area (CA) innervated by each cutaneous nerve was delineated in at least six cats by brushing the hair in the CA with a small watercolor brush while recording from the nerve. Mapping of adjacent CA revealed larger overlap zones (OZ) than were noted in the dog. Remarkable findings were that the brachiocephalic nerve arose from the axillary nerve and the CA comparable to that supplied by the cutaneous branch of the brachiocephalic nerve in the dog was supplied by a cutaneous branch of the suprascapular nerve. The CA supplied by the communicating branch from the musculocutaneous to the median nerve was similar in both species except that the communicating branch arose proximal to any other branches of the musculocutaneous nerve in the cat, whereas it was a terminal branch in the dog. The superficial branch of the radial nerve gave off cutaneous brachial branches in the cat proximal to the lateral cutaneous antebrachial nerve. The CA of the palmar branches of the ulnar nerve did not completely overlap the CA of the palmar branches of the median nerve as occurred in the dog; thus an autonomous zone (AZ) for the CA of the palmar branches of the median nerve is present in the cat, whereas no AZ existed for the CA of this nerve in the dog.

  5. Electrophysiologic studies of cutaneous nerves of the thoracic limb of the dog.

    Science.gov (United States)

    Kitchell, R L; Whalen, L R; Bailey, C S; Lohse, C L

    1980-01-01

    The cutaneous innervation of the thoracic limb was investigated in 36 barbiturate-anesthetized dogs, using electrophysiologic techniques. The cutaneous area (CA) innervated by each cutaneous nerve was delineated in at least five dogs by stroking the hair in the area with a small watercolor brush while recording from the nerve. Mapping of adjacent CA revealed areas of considerable overlapping. The part of the CA of a given nerve supplied by only that nerve is referred to as its autonomous zone. Of all nerves arising from the brachial plexus, only the suprascapular, subscapular, lateral thoracic, thoracodorsal, and cranial and caudal pectoral nerves lacked cutaneous afferents. The dorsal cutaneous branch of C6 had a CA, but no grossly demonstrable dorsal cutaneous branches for C7 C8, or T1 were found. The cervical nerves had ventral cutaneous branches, but no lateral cutaneous branches. Thoracic nerves T2-T4 had dorsal, ventral, and lateral cutaneous branches. The cutaneous branches of the brachiocephalic, axillary, musculocutaneous, radial, median, and ulnar nerves all had CA which were overlapped by adjacent CA, thus their autonomous zones were much smaller than the cutaneous areas usually depicted for these nerves in anatomy and neurology textbooks.

  6. Electrophysiological study of transport systems in isolated perfused pancreatic ducts: properties of the basolateral membrane

    DEFF Research Database (Denmark)

    Novak, I; Greger, R

    1988-01-01

    - concentration from 0 to 25 mmol/l produced fast and sustained depolarization of PDbl by 8.5 +/- 1.0 mV (n = 149). It was investigated whether the effect of HCO3- was due to a Na+-dependent transport mechanism on the basolateral membrane, where the ion complex transferred into the cell would be positively...... was monitored by electrophysiological techniques. In this report some properties of the basolateral membrane of pancreatic duct cells are described. The transepithelial potential difference (PDte) in ducts bathed in HCO3(-)-free and HCO3(-)-containing solution was -0.8 and -2.6 mV, respectively. The equivalent...... short circuit current (Isc) under similar conditions was 26 and 50 microA . cm-2. The specific transepithelial resistance (Rte) was 88 omega cm2. In control solutions the PD across the basolateral membrane (PDbl) was -63 +/- 1 mV (n = 314). Ouabain (3 mmol/l) depolarized PDbl by 4.8 +/- 1.1 mV (n = 6...

  7. Language specificity of lexical-phonological therapy in bilingual aphasia: A clinical and electrophysiological study.

    Science.gov (United States)

    Radman, Narges; Spierer, Lucas; Laganaro, Marina; Annoni, Jean-Marie; Colombo, Françoise

    2016-08-01

    Based on findings for overlapping representations of bilingual people's first (L1) and second (L2) languages, unilingual therapies of bilingual aphasia have been proposed to benefit the untrained language. However, the generalisation patterns of intra- and cross-language and phonological therapy and their neural bases remain unclear. We tested whether the effects of an intensive lexical-phonological training (LPT) in L2 transferred to L1 word production in a Persian-French bilingual stroke patient with Broca's aphasia. Language performance was assessed using the Bilingual Aphasia Test, a 144-item picture naming (PN) task and a word-picture verification (WPV) task. Electroencephalography (EEG) was recorded during PN and WPV in both languages before and after an LPT in French on a wordlist from the PN task. After the therapy, naming improved only for the treated L2 items. The naming performance improved neither in the untrained L2 items nor in the corresponding items in L1. EEG analyses revealed a Language x Session topographic interaction at 540 ms post-stimulus, driven by a modification of the electrophysiological response to the treated L2 but not L1 items. These results indicate that LPT modified the brain networks engaged in the phonological-phonetic processing during naming only in the trained language for the trained items.

  8. Heterogeneity of Monosymptomatic Resting Tremor in a Prospective Study: Clinical Features, Electrophysiological Test, and Dopamine Transporter Positron Emission Tomography

    Institute of Scientific and Technical Information of China (English)

    Hua-Guang Zheng; Rong Zhang; Xin Li; Fang-Fei Li; Ya-Chen Wang; Xue-Mei Wang; Ling-Long Lu

    2015-01-01

    Background:The relationship between monosymptomatic resting tremor (mRT) and Parkinson's disease (PD) remains controversial.In this study,we aimed to assess the function ofpresynaptic dopaminergic neurons in patients with mRT by dopamine transporter positron emission tomography (DAT-PET) and to evaluate the utility of clinical features or electrophysiological studies in differential diagnosis.Methods:Thirty-three consecutive patients with mRT were enrolled prospectively.The Unified Parkinson's Disease Rating Scale and electromyography were tested before DAT-PET.Striatal asymmetry index (SAI) was calculated,and a normal DAT-PET was defined as a SAI of <15%.Scans without evidence of dopaminergic deficits (SWEDDs) were diagnosed in patients with a subsequent normal DAT-PET and structural magnetic resonance imaging.Results:Twenty-eight mRT patients with a significant reduction in uptake of DAT binding in the striatum were diagnosed with PD,while the remained 5 with a normal DAT-PET scan were SWEDDs.As for UPRDS,the dressing and hygiene score,walking in motor experiences of daily living (Part Ⅱ) and motor examination (Part Ⅲ) were significant different between two groups (P < 0.05 andP< 0.01,respectively).Bilateral tremor was more frequent in the SWEDDs group (P < 0.05).The frequency of resting tremor and the amplitude of postural tremor tend to be higher in the SWEDDs group (P =0.08 and P =0.05,respectively).Conclusions:mRT is heterogeneous in presynaptic nigrostriatal dopaminergic degeneration,which can be determined by DAT-PET brain imaging.Clinical and electrophysiological features may provide clues to distinguish PD from SWEDDs.

  9. Carpal tunnel syndrome assessed with diffusion tensor imaging: Comparison with electrophysiological studies of patients and healthy volunteers

    International Nuclear Information System (INIS)

    Wang, Chien-Kuo; Jou, I-Ming; Huang, Han-Wei; Chen, Pei-Yin; Tsai, Hong-Ming; Liu, Yi-Sheng; Lin, Chou-Ching K.

    2012-01-01

    The main goal of this study was to investigate the applicability of parameters derived from diffusion tension imaging (DTI) in diagnosing carpal tunnel syndrome (CTS). Forty subjects were recruited, of which 19 were normal controls and 21 belonged to the CTS group. DTI of median nerves evaluated at 4 levels of the wrist (distal radius, pisiform bone, middle portion of the carpal tunnel, and hamate bone) and conventional MRI of the wrist was performed in normal and CTS subjects in two finger postures (extension and flexion). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were derived from DTI, and parameters related to abnormal hyperintensity of the median nerve were derived from conventional MRI. Electrophysiological tests, including nerve conduction velocity and F wave were also performed for comparison. The results of FA and ADC measurements did not depend on the measuring location and finger posture. Mean FA was decreased while mean ADC was increased by CTS. FA and ADC at the middle portion of the carpal tunnel was 0.47 ± 0.05 and 1.37 ± 0.12 (×10 −3 mm 2 /s) for the control group and 0.42 ± 0.04 and 1.50 ± 0.15 (×10 −3 mm 2 /s) for the CTS group, respectively. The linear correlations of FA and ADC versus electrophysiological indicators of CTS were significant (R 2 ranged from 0.09 to 0.36), indicating FA and ADC from DTI had significant correlation with the existence and severity of CTS.

  10. Dopaminergic modulation of mitral cell activity in the frog olfactory bulb: a combined radioligand binding-electrophysiological study

    International Nuclear Information System (INIS)

    Duchamp, A.; Moyse, E.; Delaleu, J.-C.; Coronas, V.; Duchamp-Viret, P.

    1997-01-01

    Dopamine content in the amphibian olfactory bulb is supplied by interneurons scattered among mitral cells in the external plexiform/mitral cell layer. In mammals, dopamine has been found to be involved in various aspects of bulbar information processing by influencing mitral cell odour responsiveness. Dopamine action in the bulb depends directly on the localization of its receptor targets, found to be mainly of the D 2 type in mammals. The present study assessed, in the frog, both the anatomical localization of D 2 -like, radioligand-labelled receptors of dopamine and the in vivo action of dopamine on unitary mitral cell activity in response to odours delivered over a wide range of concentrations. The [ 125 I]iodosulpride-labelled D 2 binding sites were visualized on frozen sagittal sections of frog brains by film radioautography. The sites were found to be restricted to the external plexiform/mitral cell layer; other layers of the olfactory bulb were devoid of specific labelling. Electrophysiological recordings of mitral unit activity revealed that dopamine or its agonist apomorphine induced a drastic reduction of spontaneous firing rate of mitral cells in most cases without altering odour intensity coding properties of these cells. Moreover, pre-treatment with the D 2 antagonist eticlopride blocked the dopamine-induced reduction of mitral cell spontaneous activity.In the frog olfactory bulb, both anatomical localization of D 2 -like receptors and functional data on dopamine involvement in information processing differ from those reported in mammals. This suggests a phylogenetic evolution of dopamine action in the olfactory bulb. In the frog, anatomical data perfectly corroborate electrophysiological results, together strongly suggesting a direct action of dopamine on mitral cells. In a physiologically operating system, such an action would result in a global improvement of signal-to-noise ratio. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights

  11. An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats.

    Science.gov (United States)

    Souza, Deise Elizabeth; Pereira, Marcia Oliveira; Bernardo, Luciana Camargo; Carmo, Fernanda Santos; Fonseca, Adenilson de Souza da; Bernardo-Filho, Mario

    2011-01-01

    Cassia angustifolia Vahl (senna) is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid) lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-⁹⁹m (⁹⁹mTc) and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na⁹⁹mTcO₄)in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na⁹⁹mTcO₄ and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na⁹⁹mTcO₄ in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na⁹⁹mTcO₄ are conducted in patients who are using senna extract.

  12. An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats

    Directory of Open Access Journals (Sweden)

    Deise Elizabeth Souza

    2011-01-01

    Full Text Available Cassia angustifolia Vahl (senna is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-99m (99mTc and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na99mTcO4in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na99mTcO4 and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na99mTcO4 in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na99mTcO4 are conducted in patients who are using senna extract.

  13. An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Deise Elizabeth; Pereira, Marcia Oliveira; Bernardo, Luciana Camargo; Carmo, Fernanda Santos, E-mail: marciaoliveira.13@terra.com.b [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Lab. de Radiofarmacia Experimental; Fonseca, Adenilson de Souza da [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. Biomedico. Dept. de Ciencias Fisiologicas; Bernardo-Filho, Mario [Instituto Nacional do Cancer (INCA), Rio de Janeiro, RJ (Brazil). Coordenadoria de Pesquisa

    2011-07-01

    Cassia angustifolia Vahl (senna) is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid) lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-99m ({sup 99m}Tc) and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na{sup 99m}TcO{sub 4}) in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na{sup 99m}TcO{sub 4} and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na{sup 99m}TcO{sub 4} in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na{sup 99m}TcO{sub 4} are conducted in patients who are using senna extract. (author)

  14. An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats

    International Nuclear Information System (INIS)

    Souza, Deise Elizabeth; Pereira, Marcia Oliveira; Bernardo, Luciana Camargo; Carmo, Fernanda Santos; Fonseca, Adenilson de Souza da; Bernardo-Filho, Mario

    2011-01-01

    Cassia angustifolia Vahl (senna) is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid) lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-99m ( 99m Tc) and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na 99m TcO 4 ) in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na 99m TcO 4 and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na 99m TcO 4 in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na 99m TcO 4 are conducted in patients who are using senna extract. (author)

  15. [Clinical and electrophysiologic studies on epileptic negative myoclonus in atypical benign partial epilepsy of childhood].

    Science.gov (United States)

    Yang, Zhi-xian; Liu, Xiao-yan; Qin, Jiong; Zhang, Yue-hua; Bao, Xin-hua; Chang, Xing-zhi; Wu, Ye; Xiong, Hui

    2008-12-01

    To investigate the clinical, neurophysiologic characteristics and therapeutic considerations of epileptic negative myoclonus (ENM) in atypical benign partial epilepsy of childhood (ABPE). Video-EEG monitoring with outstretched arm tests were carried out in 17 patients, and 9 of them were examined with simultaneous electromyography (EMG). The ENM manifestations, electrophysiologic features and responses to antiepileptic drugs (AED) were analyzed. Seventeen patients were diagnosed as having benign childhood epilepsy with centrotemporal spikes (BECT) during the early course of the disease and were treated with AED. During the course of the disease, hand trembling, objects dropping, head nodding and instability during standing might be clues for ENM occurrence. ENM had been confirmed in our patients by outstretched arm tests during video-EEG recording. The ictal EEG showed that high-amplitude spikes followed by a slow wave over the contralateral motor areas. This was further confirmed by time-locked silent EMG in 9 patients. During ENM occurrence or recurrence, the habitual seizures and interictal discharges were exaggerated. Atypical absence seizures also occurred in 6 patients. The alteration of therapeutic options of AED relating to ENM appearance in some patients included the add-on therapy with carbamazepine (CBZ), oxcarbazepine, phenobarbital, or withdrawal of valproate (VPA). ENM was controlled in most cases by using VPA, clonazepam (CZP) and corticosteroid with different combination. ENM could occur during the course of ABPE. Outstretching arm tests during video-EEG monitoring in combination with EMG was essential to confirm ENM. The ENM occurrence was always associated with the frequency increasing of habitual seizures and the aggravation of interictal discharges. Some AED such as CBZ might induce ENM. VPA, benzodiazepines and corticosteroid with different combination were relatively effective in treatment of ENM.

  16. Brain tumor magnetic targeting and biodistribution of superparamagnetic iron oxide nanoparticles linked with 70-kDa heat shock protein study by nonlinear longitudinal response

    International Nuclear Information System (INIS)

    Shevtsov, Maxim A.; Nikolaev, Boris P.; Ryzhov, Vyacheslav A.; Yakovleva, Ludmila Y.; Dobrodumov, Anatolii V.; Marchenko, Yaroslav Y.; Margulis, Boris A.; Pitkin, Emil; Guzhova, Irina V.

    2015-01-01

    Brain tumor targeting efficiency and biodistribution of the superparamagnetic nanoparticles conjugated with heat shock protein Hsp70 (SPION–Hsp70) were evaluated in experimental glioma model. Synthesized conjugates were characterized using the method of longitudinal nonlinear response of magnetic nanoparticles to a weak ac magnetic field with measurements of second harmonic of magnetization (NLR-M 2 ). Cellular interaction of magnetic conjugates was analyzed in 9L glioma cell culture. The biodistribution of the nanoparticles and their accumulation in tumors was assessed by the latter approach as well. The efficacy of Hsp70-conjugates for contrast enhancement in the orthotopic model of 9L glioma was assessed by MR imaging (11 T). Magnetic nanoparticles conjugated with Hsp70 had the relaxivity properties of the MR-negative contrast agents. Morphological observation and cell viability test demonstrated good biocompatibility of Hsp70-conjugates. Analysis of the T 2 -weighted MR scans in tumor-bearing rats demonstrated the high efficacy of Hsp70-conjugates in contrast enhancement of the glioma in comparison to non-conjugated nanoparticles. High contrast enhancement of the glioma was provided by the accumulation of the SPION–Hsp70 particles in the glioma tissue (as shown by the histological assay). Biodistribution analysis by NLR-M 2 measurements evidenced the many-fold increase (~40) in the tumor-to-normal brain uptake ratio in the Hsp70-conjugates treated animals. Biodistribution pattern of Hsp70-decorated nanoparticles differed from that of non-conjugated SPIONs. Coating of the magnetic nanoparticles with Hsp70 protein enhances the tumor-targeting ability of the conjugates that could be applied in the MR imaging of the malignant brain tumors. - Highlights: • Second-harmonic nonlinear magnetic response is used for biodistribution analysis. • NLR-M 2 ensures high sensibility in detection of SPIONs in tissue. • SPION–Hsp70 conjugates effectively target the

  17. Effects of anesthetics on vesicular monoamine transporter type 2 binding to 18F-FP-(+)-DTBZ: a biodistribution study in rat brain

    International Nuclear Information System (INIS)

    Chen, Zhengping; Tang, Jie; Liu, Chunyi; Li, Xiaomin; Huang, Hongbo; Xu, Xijie; Yu, Huixin

    2016-01-01

    Objectives: The in vivo binding analysis of vesicular monoamine transporter type 2 (VMAT2) to radioligand has provided a means of investigating related disorders. Anesthesia is often inevitable when the investigations are performed in animals. In the present study, we tested effects of four commonly-used anesthetics: isoflurane, pentobarbital, chloral hydrate and ketamine, on in vivo VMAT2 binding to 18 F-FP-(+)-DTBZ, a specific VMAT2 radioligand, in rat brain. Methods: The transient equilibrium time window for in vivo binding of 18 F-FP-(+)-DTBZ after a bolus injection was firstly determined. The brain biodistribution studies under anesthetized and awake rats were then performed at the equilibrium time. Standard uptake values (SUVs) of the interest brain regions: the striatum (ST), hippocampus (HP), cortex (CX) and cerebellum (CB) were obtained; and ratios of tissue to cerebellum were calculated. Results: Isoflurane and pentobarbital did not alter distribution of 18 F-FP-(+)-DTBZ in the brain relative to the awake group; neither SUVs nor ratios of ST/CB and HP/CB were altered significantly. Chloral hydrate significantly increased SUVs of all the brain regions, but did not significantly alter ratios of ST/CB and HP/CB. Ketamine significantly increased SUVs of the striatum, hippocampus and cortex, and insignificantly increased the SUV of the cerebellum; consequently, ketamine significantly increased ratios of ST/CB and HP/CB. Conclusions: It is concluded that in vivo VMAT2 binding to 18 F-FP-(+)-DTBZ are not altered by isoflurane and pentobarbital, but altered by chloral hydrate and ketamine. Isoflurane and pentobarbital may be promising anesthetic compounds for investigating in vivo VMAT2 binding. Further studies are warranted to investigate the interactions of anesthetics with VMAT2 binding potential with in vivo PET studies.

  18. Studies of the radiolabeling and biodistribution of substance P using lutetium-177 as a radiotracer; Estudo da marcacao e biodistribuicao da substancia P utilizando lutecio-177 como radiotracador

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Clarice Maria de

    2011-07-01

    -DOTA-SP, radiolabeled in the absence and presence of methionine, using human M059J U-87 MG glioma cells and, showed the effect of oxidation of methionine on the cells binding. Biodistribution studies were performed in Nude mice with tumor model and Balb-c mice. Highest radiochemical purity (> 95%) associated with the highest specific activity of '1{sup 77}Lu-DOTA-SP when the reaction time was 30 minutes, temperature of 90 degree C, 10 g{mu} of DOTA-SP, and the activity of {sup 177}Lu of 185 MBq. The radiolabeled SP in optimized conditions remained stable at 2-8 degree C and in human serum for 4 hours. In vitro studies showed the binding to cell receptors and this binding was reduced when the peptide was presented in its oxidized form. The addition of methionine combined with gentisic acid prevented the oxidation of peptide and increased the stability of the labeled compound, particularly with high activity of {sup 177}Lu, when using larger mass of DOTA-SP. In vivo studies results showed a favorable biodistribution kinetics of the compound and ability to bind to tumor cells. {sup 177}Lu-DOTA-SP can be a useful tool for in vivo studies due to ease preparation, high stability and affinity for tumor cells. (author)

  19. Stealth lipid polymer hybrid nanoparticles loaded with rutin for effective brain delivery - comparative study with the gold standard (Tween 80): optimization, characterization and biodistribution.

    Science.gov (United States)

    Ishak, Rania A H; Mostafa, Nada M; Kamel, Amany O

    2017-11-01

    The blood-brain barrier is considered the leading physiological obstacle hindering the transport of neurotherapeutics to brain cells. The application of nanotechnology coupled with surfactant coating is one of the efficacious tactics overcoming this barrier. The aim of this study was to develop lipid polymer hybrid nanoparticles (LPHNPs), composed of a polymeric core and a phospholipid shell entangled, for the first time, with PEG-based surfactants (SAA) viz. TPGS or Solutol HS 15 in comparison with the gold standard Tween 80, aiming to enhance brain delivery and escape opsonization. LPHNPs were successfully prepared using modified single-step nanoprecipitation technique, loaded with the flavonoid rutin (RU), extracted from the flowers of Calendula officinalis L., and recently proved as a promising anti-Alzheimer. The effect of the critical process parameters (CPP) viz. PLGA amount, W lecithin /W PLGA ratio, and Tween 80 concentration on critical quality attributes (CQA); entrapment, size and size distribution, was statistically analyzed via design of experiments, and optimized using the desirability function. The optimized CPP were maintained while substituting Tween 80 with other PEG-SAA. All hybrid particles exhibited spherical shape with perceptible lipid shells. The biocompatibility of the prepared NPs was confirmed by hemolysis test. The pharmacokinetic assessments, post-intravenous administration to rats, revealed a significant higher RU bioavailability for NPs relative to drug solution. Biodistribution studies proved non-significant differences in RU accumulation within brain, but altered phagocytic uptake among various LPHNPs. The present study endorses the successful development of LPHNPs using PEG-SAA, and confirms the prospective applicability of TPGS and Solutol in enhancing brain delivery.

  20. Heterogeneity of Monosymptomatic Resting Tremor in a Prospective Study: Clinical Features, Electrophysiological Test, and Dopamine Transporter Positron Emission Tomography

    Directory of Open Access Journals (Sweden)

    Hua-Guang Zheng

    2015-01-01

    Conclusions: mRT is heterogeneous in presynaptic nigrostriatal dopaminergic degeneration, which can be determined by DAT-PET brain imaging. Clinical and electrophysiological features may provide clues to distinguish PD from SWEDDs.

  1. Two anti-angiogenic TKI-PET tracers, [11C]axitinib and [11C]nintedanib: Radiosynthesis, in vivo metabolism and initial biodistribution studies in rodents

    International Nuclear Information System (INIS)

    Slobbe, Paul; Poot, Alex J.; Haumann, Rianne; Schuit, Robert C.; Windhorst, Albert D.; Dongen, Guus A.M.S. van

    2016-01-01

    Introduction: Tyrosine kinase inhibitors (TKIs) are very attractive targeted drugs, although a large portion of patients remains unresponsive. PET imaging with EGFR targeting TKIs ([ 11 C]erlotinib and [ 18 F]afatinib) showed promise in identifying treatment sensitive tumors. The aim of this study was to synthesize two anti-angiogenic TKI tracers, [ 11 C]axitinib and [ 11 C]nintedanib, and to evaluate their potential for PET. Methods: Following successful tracer synthesis, biodistribution studies in VU-SCC-OE and FaDu xenograft bearing mice were performed. Furthermore, tracer stability studies in mice were performed employing (radio-)HPLC and LC–MS/MS techniques. For [ 11 C]nintedanib an LC–MS/MS method was developed to detect the primary carboxylic acid metabolite, resulting from methylester cleavage, in plasma and tumors, because this metabolite is postulated to be important for nintedanib efficacy. LC–MS/MS was also explored to assess the metabolic fate of [ 11 C]axitinib in vivo, since axitinib has an isomerizable double bond. Results: [ 11 C]axitinib and [ 11 C]nintedanib were successfully synthesized with 10.5 ± 2.6% and 25.6 ± 3.3% radiochemical yield (corrected for decay), respectively. Biodistribution studies only demonstrated tumor uptake of [ 11 C]nintedanib in FaDu xenografts of 1.66 ± 0.02% ID/g at 60 min p.i. In vivo stability analysis of [ 11 C]axitinib at 45 min p.i. revealed the formation of predominantly non-polar metabolites (36.6 ± 6.8% vs 47.1 ± 8.4% of parent tracer and 16.3 ± 2.1% of polar metabolites), while for [ 11 C]nintedanib mostly polar metabolites were found (70.9 ± 4.1 vs 26.7 ± 3.9% of parent tracer and only 2.4 ± 1.6 of a non-polar metabolites). No isomerization of [ 11 C]axtinib was observed in vivo; however, a sulfoxide metabolite could be detected using LC–MS/MS. For [ 11 C]nintedanib, LC–MS/MS revealed formation of the reported primary carboxylic acid metabolite when in vitro plasma incubations were performed

  2. Biodistribution of 99Mo in rats

    International Nuclear Information System (INIS)

    Souza, Raphael Sancho Sisley de; Ribeiro, Bianca da Silva; Dantas, Ana Leticia Almeida; Dantas, Bernardo Maranhao; Bernardo Filho, Mario

    2009-01-01

    The modification of 99 Mo standard metabolism in the presence of MDP would alter the dosimetry of this radionuclide in nuclear medicine patients. Therefore, the objective of this work is to evaluate the influence of MDP in the biodistribution of 99 Mo. Wistar rats were divided in two groups of six animals, being inoculated respectively 99 Molibdate and 99 Mo+MDP via plex ocular. The biodistribution study was carried out after 10 and 120 minutes respectively. The organs were counted with a NaI(Tl) detector. The uptake values did not present significant differences among the groups. An in vitro study through planar chromatography was carried out to determine the affinity between molybdenum and MDP. The results show that 99 Mo has low affinity both to propanone and NaCl-0.9% solution. However, 99 Mo in the presence of MDP presented affinity to NaCl-0.9% solution and low affinity to propanone suggesting that 99 Mo was bound to MDP under the conditions of the experiment. (author)

  3. Electrosteric stealth Rivastigmine loaded liposomes for brain targeting: preparation, characterization, ex vivo, bio-distribution and in vivo pharmacokinetic studies.

    Science.gov (United States)

    Nageeb El-Helaly, Sara; Abd Elbary, Ahmed; Kassem, Mohamed A; El-Nabarawi, Mohamed A

    2017-11-01

    Being one of the highly effective drugs in treatment of Alzheimer's disease, Rivastigmine brain targeting is highly demandable, therefore liposomal dispersion of Rivastigmine was prepared containing 2 mol% PEG-DSPE added to Lecithin, Didecyldimethyl ammonium bromide (DDAB), Tween 80 in 1:0.02:0.25 molar ratio. A major challenge during the preparation of liposomes is maintaining a stable formulation, therefore the aim of our study was to increase liposomal stability by addition of DDAB to give an electrostatic stability and PEG-DSPE to increase stability by steric hindrance, yielding what we called an electrosteric stealth (ESS) liposomes. A medium nano-sized liposome (478 ± 4.94 nm) with a nearly neutral zeta potential (ZP, -8 ± 0.2 mV) and an entrapment efficiency percentage of 48 ± 6.22 was prepared. Stability studies showed no major alteration after three months storage period concerning particle size, polydispersity index, ZP, entrapment efficiency and in vitro release study confirming the successful formation of a stable liposomes. No histopathological alteration was recorded for ESS liposomes of the sheep nasal mucosa. While ESS liposomes showed higher % of drug permeating through the sheep nasal mucosa (48.6%) than the drug solution (28.7%). On completing the in vivo pharmacokinetic studies of 36 rabbits showed 424.2% relative bioavailability of the mean plasma levels of the formula ESS compared to that of RHT intranasal solution and 486% relative bioavailability of the mean brain levels.

  4. IND-directed safety and biodistribution study of intravenously injected cetuximab-IRDye800 in cynomolgus macaques.

    Science.gov (United States)

    Zinn, Kurt R; Korb, Melissa; Samuel, Sharon; Warram, Jason M; Dion, David; Killingsworth, Cheryl; Fan, Jinda; Schoeb, Trenton; Strong, Theresa V; Rosenthal, Eben L

    2015-02-01

    The use of receptor-targeted antibodies conjugated to fluorophores is actively being explored for real-time imaging of disease states; however, the toxicity of the bioconjugate has not been assessed in non-human primates. To this end, the in vivo toxicity and pharmacokinetics of IRDye800 conjugated to cetuximab (cetuximab-IRDye800; 21 mg/kg; equivalent to 250 mg/m(2) human dose) were assessed in male cynomolgus monkeys over 15 days following intravenous injection and compared with an unlabeled cetuximab-dosed control group. Cetuximab-IRDye800 was well tolerated. There were no infusion reactions, adverse clinical signs, mortality, weight loss, or clinical histopathology findings. The plasma half-life for the cetuximab-IRDye800 and cetuximab groups was equivalent (2.5 days). The total recovered cetuximab-IRDye800 in all tissues at study termination was estimated to be 12 % of the total dose. Both cetuximab-IRDye800 and cetuximab groups showed increased QTc after dosing. The QTc for the cetuximab-dosed group returned to baseline by day 15, while the QTc of the cetuximab-IRDye800 remained elevated compared to baseline. IRDye800 in low molar ratios does not significantly impact cetuximab half-life or result in organ toxicity. These studies support careful cardiac monitoring (ECG) for human studies using fluorescent dyes.

  5. Combined chelation based on glycosyl-mono- and bis-hydroxypyridinones for aluminium mobilization: solution and biodistribution studies.

    Science.gov (United States)

    Chaves, Sílvia; Dron, Paul I; Danalache, Florina A; Sacoto, Diana; Gano, Lurdes; Santos, M Amélia

    2009-11-01

    Taking into account the recognized interest of a poly-pharmacological strategy in chelation therapy, a study of aluminium combined chelation based on 3-hydroxy-4-pyridinone (3,4-HP) compounds with complementary properties, associated to different denticity, size and extrafunctionality, is presented herein. In particular, Al-chelation has been explored, using a tetradentate IDA bis-(3,4-HP) ligand, L, and two N-glycosyl mono-(3,4-HP) derivatives (A or B). Combined complexation studies with the tetradentate and the most promising bidentate ligand (A) evidenced the formation of ternary complexes with high thermodynamic stability (Al-L-A) being the predominant species at physiological pH. In vivo studies on the ability for radiotracer ((67)Ga) removal from loaded mice, as a model of aluminium accumulation in body, have shown that the simultaneous administration to (67)Ga-loaded mice of a mono- and a bis-(3,4-HP) chelator (e.g. A and L) leads to a rapid metal elimination from main organs and whole animal model. This may be rationalized by coadjuvation and eventual synergistic effects, due to complementary accessibility of the chelators to different cellular compartments.

  6. Current concepts in nuclear pore electrophysiology.

    Science.gov (United States)

    Bustamante, José Omar

    2006-01-01

    Over 4 decades ago, microelectrode studies of in situ nuclei showed that, under certain conditions, the nuclear envelope (NE) behaves as a barrier opposing the nucleocytoplasmic flow of physiological ions. As the nuclear pore complexes (NPCs) of the NE are the only pathways for direct nucleocytoplasmic flow, those experiments implied that the NPCs are capable of restricting ion flow. These early studies validated electrophysiology as a useful approach to quantify some of the mechanisms by which NPCs mediate gene activity and expression. Since electron microscopy (EM) and other non-electrophysiological investigations, showed that the NPC lumen is a nanochannel, the opinion prevailed that the NPC could not oppose the flow of ions and, therefore, that electrophysiological observations resulted from technical artifacts. Consequently, the initial enthusiasm with nuclear electrophysiology faded out in less than a decade. In 1990, nuclear electrophysiology was revisited with patch-clamp, the most powerful electrophysiological technique to date. Patch-clamp has consistently demonstrated that the NE has intrinsic ion channel activity. Direct demonstrations of the NPC on-off ion channel gating behavior were published for artificial conditions in 1995 and for intact living nuclei in 2002. This on-off switching/gating behavior can be interpreted in terms of a metastable energy barrier. In the hope of advancing nuclear electrophysiology, and to complement the other papers contained in this special issue of the journal, here I review some of the main technical, experimental, and theoretical issues of the field, with special focus on NPCs.

  7. Brain tumor magnetic targeting and biodistribution of superparamagnetic iron oxide nanoparticles linked with 70-kDa heat shock protein study by nonlinear longitudinal response

    Energy Technology Data Exchange (ETDEWEB)

    Shevtsov, Maxim A., E-mail: shevtsov-max@mail.ru [Institute of Cytology of the Russian Academy of Sciences (RAS), Tikhoretsky Ave. 4, St. Petersburg 194064 (Russian Federation); A.L. Polenov Russian Research Scientific Institute of Neurosurgery, Mayakovsky str. 12, St. Petersburg 191014 (Russian Federation); Nikolaev, Boris P. [Research Institute of Highly Pure Biopreparations, Pudozhskaya str. 12, St. Petersburg 197110 (Russian Federation); Ryzhov, Vyacheslav A. [Petersburg Nuclear Physics Institute, NRC Kurchatov Institute, Gatchina 188300 (Russian Federation); Yakovleva, Ludmila Y. [Research Institute of Highly Pure Biopreparations, Pudozhskaya str. 12, St. Petersburg 197110 (Russian Federation); Dobrodumov, Anatolii V. [Institute of Macromolecular Compounds of the Russian Academy of Sciences (RAS), Bolshoi pr. 31, St. Petersburg 199004 (Russian Federation); Marchenko, Yaroslav Y. [Research Institute of Highly Pure Biopreparations, Pudozhskaya str. 12, St. Petersburg 197110 (Russian Federation); Margulis, Boris A. [Institute of Cytology of the Russian Academy of Sciences (RAS), Tikhoretsky Ave. 4, St. Petersburg 194064 (Russian Federation); Pitkin, Emil [The Wharton School, University of Pennsylvania, 3730 Walnut St., Philadelphia, PA 19104 (United States); Guzhova, Irina V. [Institute of Cytology of the Russian Academy of Sciences (RAS), Tikhoretsky Ave. 4, St. Petersburg 194064 (Russian Federation)

    2015-08-15

    Brain tumor targeting efficiency and biodistribution of the superparamagnetic nanoparticles conjugated with heat shock protein Hsp70 (SPION–Hsp70) were evaluated in experimental glioma model. Synthesized conjugates were characterized using the method of longitudinal nonlinear response of magnetic nanoparticles to a weak ac magnetic field with measurements of second harmonic of magnetization (NLR-M{sub 2}). Cellular interaction of magnetic conjugates was analyzed in 9L glioma cell culture. The biodistribution of the nanoparticles and their accumulation in tumors was assessed by the latter approach as well. The efficacy of Hsp70-conjugates for contrast enhancement in the orthotopic model of 9L glioma was assessed by MR imaging (11 T). Magnetic nanoparticles conjugated with Hsp70 had the relaxivity properties of the MR-negative contrast agents. Morphological observation and cell viability test demonstrated good biocompatibility of Hsp70-conjugates. Analysis of the T{sub 2}-weighted MR scans in tumor-bearing rats demonstrated the high efficacy of Hsp70-conjugates in contrast enhancement of the glioma in comparison to non-conjugated nanoparticles. High contrast enhancement of the glioma was provided by the accumulation of the SPION–Hsp70 particles in the glioma tissue (as shown by the histological assay). Biodistribution analysis by NLR-M{sub 2} measurements evidenced the many-fold increase (~40) in the tumor-to-normal brain uptake ratio in the Hsp70-conjugates treated animals. Biodistribution pattern of Hsp70-decorated nanoparticles differed from that of non-conjugated SPIONs. Coating of the magnetic nanoparticles with Hsp70 protein enhances the tumor-targeting ability of the conjugates that could be applied in the MR imaging of the malignant brain tumors. - Highlights: • Second-harmonic nonlinear magnetic response is used for biodistribution analysis. • NLR-M{sub 2} ensures high sensibility in detection of SPIONs in tissue. • SPION–Hsp70 conjugates

  8. Biodistribution dosimetric study of radiopharmaceutical 99mTc Ixolaris in mice for melanoma diagnosis by molecular image and translational model for human beings

    International Nuclear Information System (INIS)

    Soriano, Sarah Canuto Silva

    2015-01-01

    The labeling of Ixolaris with 99m Tc was developed by Barboza et.al. (2013) aiming its use primarily in glioblastoma and after in melanoma diagnosis, a less common but very aggressive cancer and with high mortality rate. Preliminary tests on animals have proven its effectiveness of labeling but a dosimetric study to human clinical trials should be performed. This study aimed to: (1) determine the biokinetic model for the radiotracer 99m Tc-Ixolaris in mice by imaging dosimetry method; and (2) estimate the absorbed and effective dose resulting from the use of a new radiopharmaceutical for melanoma and metastases diagnosis in human beings, since a dosimetric study of new radiopharmaceuticals in animals is necessary to test them subsequently in humans and apply for registration in ANVISA. According to SPECT images, was found a latency period of 15 to 21 days for the development of lung metastasis in mice. Three C57BL6 mice, one control animal, and two animals with induced cell line B16-F10 murine melanoma were tested. The 99m Tc-Ixolaris radiopharmaceutical was administered intravenously in a caudal vein, and SPECT images were acquired 0.5 h, 1.5 h, 2.5 h, 3.5 h and 24 h post-administration for analysis and biodistribution quantification. The biokinetic model was determined and thus, obtained cumulative activity in order to estimate the absorbed dose in each organ. The mass and metabolic differences between mice and humans were considered and used to extrapolate the data acquired at different scales. Based on dose factors provided by the software MIRDOSE and Olinda (S factor), absorbed doses in irradiated target organs were calculated for the source organs, and finally the effective dose was estimated. The results indicate that for diagnostic exams conducted in human melanoma patients by administering approximately 25.7 MBq the estimated effective dose was 4.3 mSv. Comparing with effective doses obtained in other diagnostic techniques with 99m Tc, a range of effective

  9. Study of labeling, biodistribution and scintilographic images in dog of the 15-p- iodophenyl pentadecanoic acid labeling with 131I

    International Nuclear Information System (INIS)

    Oliveira, Ione Caselato

    1997-01-01

    The myocardium scintigraphy obtained after a radioactive tracer administration is a way to identify and quantify ischemic or infarct areas. The acid 15-p-iodophenyl pentadecanoic is marked with 131 I (IPPA - 131 I), through the isotopic exchange methodology in copper sulfate and ascorbic acid presence. The radiochemical purity will be evaluated by high performance liquid chromatography (HPLC) and rising chromatography in paper. The optimization of the mark conditions was done by varying time and marking temperatures where it was shown considerable mark revenue with high radiochemical purity at 120 deg C in 30 minutes. The marked mixture stays stable up the seventh day after marking. In the biological distribution studies is observed that right after the intravenous administration of the IPPA - 131 I it is achieved a considerable capitation by the cardiac muscle. The radiopharmaceutical displays a fast blood metabolizing. The scintigraphy images obtained in dogs indicates that there is a stay in heart, allowing the identification of the cardiac muscle. (author)

  10. Experimental Study of the Effects of EIPA, Losartan, and BQ-123 on Electrophysiological Changes Induced by Myocardial Stretch.

    Science.gov (United States)

    Chorro, Francisco J; Canto, Irene Del; Brines, Laia; Such-Miquel, Luis; Calvo, Conrado; Soler, Carlos; Zarzoso, Manuel; Trapero, Isabel; Tormos, Álvaro; Such, Luis

    2015-12-01

    Mechanical response to myocardial stretch has been explained by various mechanisms, which include Na(+)/H(+) exchanger activation by autocrine-paracrine system activity. Drug-induced changes were analyzed to investigate the role of these mechanisms in the electrophysiological responses to acute myocardial stretch. Multiple epicardial electrodes and mapping techniques were used to analyze changes in ventricular fibrillation induced by acute myocardial stretch in isolated perfused rabbit hearts. Four series were studied: control (n = 9); during perfusion with the angiotensin receptor blocker losartan (1 μM, n = 8); during perfusion with the endothelin A receptor blocker BQ-123 (0.1 μM, n = 9), and during perfusion with the Na(+)/H(+) exchanger inhibitor EIPA (5-[N-ethyl-N-isopropyl]-amiloride) (1 μM, n = 9). EIPA attenuated the increase in the dominant frequency of stretch-induced fibrillation (control=40.4%; losartan=36% [not significant]; BQ-123=46% [not significant]; and EIPA=22% [PII receptor antagonist losartan and the endothelin A receptor blocker BQ-123 did not modify these effects. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  11. Protective Effects of Proline-Rich Peptide in a Rat Model of Alzheimer Disease: An Electrophysiological Study.

    Science.gov (United States)

    Khalaji, Naser; Sarkissian, John; Chavushyan, Vergine; Sarkisian, Vaghinak

    2017-01-01

    Alzheimer disease (AD) is the most common form of dementia in the elderly that slowly destroys memory and cognitive functions. The disease has no cure and leads to significant structural and functional brain abnormalities. To facilitate the treatment of this disease, we aimed to investigate proline-rich peptide (PRP-1) action of hypothalamus on hippocampal (HP) neurons and dynamics of their recovery, after intracerebroventricular (ICV) injection of amyloid-β (Aβ). Experiments were carried out on 24 adult, male Albino rats (average weight: 230±30 g). The animals were randomly divided into 3 groups (control, Aβ, and Aβ plus PRP-1). Electrophysiological patterns of hippocampal neurons in response to stimulation of entorhinal cortex (EC) with high frequency stimulation (50 Hz) were studied. It was found that Aβ (25-35) suppresses the electrical activity of hippocampal neurons. The PRP-1 would return this activity to normal levels. In general, PRP-1 has protective effect against AD-related alterations induced by amyloid peptides. This protective effect is probably due to stimulation of the immune and glia system.

  12. Study on Electrophysiological Signal Monitoring of Plant under Stress Based on Integrated Op-Amps and Patch Electrode

    Directory of Open Access Journals (Sweden)

    Weiming Cai

    2017-01-01

    Full Text Available Electrophysiological signal in plant is a weak electrical signal, which can fluctuate with the change of environment. An amplification detection system was designed for plant electrical signal acquisition by using integrated op-amps (CA3140, AD620, and INA118, patch electrode, data acquisition card (NI USB-6008, computer, and shielded box. Plant electrical signals were also studied under pressure and flooding stress. The amplification detection system can make nondestructive acquisition for Aquatic Scindapsus and Guaibcn with high precision, high sensitivity, low power consumption, high common mode rejection ratio, and working frequency bandwidth. Stress experiments were conducted through the system; results show that electrical signals were produced in the leaf of Aquatic Scindapsus under the stress of pressure. Electrical signals in the up-leaf surface of Aquatic Scindapsus were stronger than the down-leaf surface. Electrical signals produced in the leaf of Guaibcn were getting stronger when suffering flooding stress. The more the flooding stress was severe, the faster the electrical signal changed, the longer the time required for returning to a stable state was, and the greater the electrical signal got at the stable state was.

  13. Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential

    International Nuclear Information System (INIS)

    Nigg, David W.

    2012-01-01

    Boron neutron capture therapy (BNCT) combines selective accumulation of 10B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1) MAC: liposomes incorporating K(nido-7-CH3(CH2)15-7,8-C2B9H11) in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K(nido-7-CH3(CH2)15-7,8-C2B9H11) in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na3 (ae-B20H17NH3), administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 ± 16.1 ppm at 48 h and to 43.9 ± 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.

  14. Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential

    Energy Technology Data Exchange (ETDEWEB)

    David W. Nigg

    2012-05-01

    Boron neutron capture therapy (BNCT) combines selective accumulation of 10B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1) MAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na3 [ae-B20H17NH3], administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 {+-} 16.1 ppm at 48 h and to 43.9 {+-} 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.

  15. Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo.

    Science.gov (United States)

    Malik, N; Wiwattanapatapee, R; Klopsch, R; Lorenz, K; Frey, H; Weener, J W; Meijer, E W; Paulus, W; Duncan, R

    2000-03-01

    Dendrimers are highly branched macromolecules of low polydispersity that provide many exciting opportunities for design of novel drug-carriers, gene delivery systems and imaging agents. They hold promise in tissue targeting applications, controlled drug release and moreover, their interesting nanoscopic architecture might allow easier passage across biological barriers by transcytosis. However, from the vast array of structures currently emerging from synthetic chemistry it is essential to design molecules that have real potential for in vivo biological use. Here, polyamidoamine (PAMAM, Starburst), poly(propyleneimine) with either diaminobutane or diaminoethane as core, and poly(ethylene oxide) (PEO) grafted carbosilane (CSi-PEO) dendrimers were used to study systematically the effect of dendrimer generation and surface functionality on biological properties in vitro. Generally, dendrimers bearing -NH(2) termini displayed concentration- and in the case of PAMAM dendrimers generation-dependent haemolysis, and changes in red cell morphology were observed after 1 h even at low concentrations (10 microg/ml). At concentrations below 1 mg/ml CSi-PEO dendrimers and those dendrimers with carboxylate (COONa) terminal groups were neither haemolytic nor cytotoxic towards a panel of cell lines in vitro. In general, cationic dendrimers were cytotoxic (72 h incubation), displaying IC(50) values=50-300 microg/ml dependent on dendrimer-type, cell-type and generation. Preliminary studies with polyether dendrimers prepared by the convergent route showed that dendrimers with carboxylate and malonate surfaces were not haemolytic at 1 h, but after 24 h, unlike anionic PAMAM dendrimers they were lytic. Cationic 125I-labelled PAMAM dendrimers (gen 3 and 4) administered intravenously (i.v.) to Wistar rats ( approximately 10 microg/ml) were cleared rapidly from the circulation (<2% recovered dose in blood at 1 h). Anionic PAMAM dendrimers (gen 2.5, 3.5 and 5.5) showed longer circulation

  16. Alteration of 99mTc-DMSA biodistribution in glomerulonephritis

    International Nuclear Information System (INIS)

    Rajic, M.; Bogicevic, M.; Ilic, S.; Vlajkovic, M.; Antic, S.; Mitic, B.; Avramovic, M.; Mitic-Zlatovic, M.; Stefanovic, V.

    2002-01-01

    The aim of this study was to assess the relation between 99T c-DMSA biodistribution and its reliability as a marker of renal function in patients with glomerular kidney diseases. Sixty-seven patients involved in this study were classified into two groups according to 99T c-DTPA clearance and serum creatinine values: the 1. group consisted of 42 patients without renal failure while the 2nd group included 25 patients with renal failure. 99T c-DMSA biodistribution was determined by measuring kidney, blood and urine activity at 2 h and 4 h. The results, compared with those of 23 healthy volunteers, indicated the quantitative alteration of 99T c-DMSA distribution in both glomerulonephritis patient groups. In reference to the control mean values of 2 h and 4 h, in patients without renal failure, kidney activity was found decreased to 52% and 57%, while the blood activity increase of 37% and 44% was recorded together with the urine activity increase of 38% and 23%. In patients with renal failure the alterations of renal and blood activity were more remarkable, but the urine loss was found to be unchanged. It is suggested that these biodistribution changes originate mainly from tubular impairment. However, in glomerulonephritis patients, altered glomerular filtration might considerably affect biodistribution of this radiopharmaceutical and limits its suitability for precise quantitative estimation of renal function. (author)

  17. Neurotensin effects on N-type calcium currents among rat pallidal neurons: an electrophysiological and immunohistochemical study.

    Science.gov (United States)

    Martorana, Alessandro; Martella, Giuseppina; D'Angelo, Vincenza; Fusco, Francesca Romana; Spadoni, Francesca; Bernardi, Giorgio; Stefani, Alessandro

    2006-10-01

    The tridecapeptide neurotensin (NT) is involved in the modulation of dopamine (DA)-mediated functions in the nigrostriatal and mesocorticolimbic pathways. Its relevance in mammalian globus pallidus (GP) is questioned. A recent electrophysiological study on GP slices described NT-mediated robust membrane depolarization, depending upon the suppression of potassium conductance and/or the activation of cation current. Here, we have studied whether NT also affected high-voltage-activated calcium (Ca(2+)) currents, by means of whole-cell recordings on isolated GP neurons. In our hands, the full peptide and the segment NT8-13 reversibly inhibited N-like Ca(2+) current in about 60% of the recorded dissociated neurons, irrespective of their capacitance. The NT-mediated modulation showed no desensitization and was antagonized by the NT1 antagonists SR48692 and SR142948. These results imply an abundant expression of NTS(1) on GP cell somata. Then, we performed a light and immunofluorescence-confocal microscopy study of NTS(1) localization among GP neurons. We found that NTS(1) is localized in about 56% of GP neurons in both subpopulations of neurons, namely parvalbumin positive and negative. We conclude that NT, likely released from the striatal terminals in GP, acts through the postsynaptic NTS(1) preferentially localized in the lateral aspects of the GP. These data suggest a new implication (neither merely presynaptic nor simply "excitatory") for NT in the modulation of GP firing pattern. In addition, NT might have a role in affecting the interplay among the endogenous release of GABA/glutamate and DA. This hypothesis might have implications on both sensori-motor and associative functions of the GP and should be tested in DA-denervated disease models.

  18. Electrophysiological evidence for the modulation of retrieval orientation by depth of study processing.

    Science.gov (United States)

    Rugg, M D; Allan, K; Birch, C S

    2000-07-01

    Event-related potentials (ERPs) were employed to investigate whether brain activity elicited by retrieval cues in a memory test varies according to the encoding task undertaken at study. Two recognition memory test blocks were administered, preceded, in one case, by a "shallow" study task (alphabetic judgement) and, in the other case, by a "deep" task (sentence generation). ERPs elicited by the new words in each test block differed, the ERPs elicited in the block following the shallow study task exhibiting the more positive-going waveforms. This finding was taken as evidence that subjects adopt different "retrieval sets" when attempting to retrieve items that had been encoded in terms of alphabetic versus semantic attributes. Differences between the ERPs elicited by correctly classified old and new words (old/new effects) also varied with encoding task. The effects for deeply studied words resembled those found in previous ERP studies of recognition memory, whereas old/new effects for shallowly studied words were confined to a late-onsetting, right frontal positivity. Together, the findings indicate that the depth of study processing influences two kinds of memory-related neural activity, associated with memory search operations, and the processing of retrieved information, respectively.

  19. Biodistribution imaging of a paclitaxel-hyaluronan bioconjugate

    Energy Technology Data Exchange (ETDEWEB)

    Banzato, Alessandra; Rondina, Maria [Department of Oncology and Surgical Sciences, University of Padua, I-35128 Padova (Italy); Melendez-Alafort, Laura; Zangoni, Elena; Nadali, Anna [Department of Pharmaceutical Sciences, University of Padua, Padova (Italy); Renier, Davide [Fidia Farmaceutici, Abano Terme (Italy); Moschini, Giuliano [Department of Physics, University of Padua, Padova (Italy); Mazzi, Ulderico [Department of Pharmaceutical Sciences, University of Padua, Padova (Italy); Zanovello, Paola [Department of Oncology and Surgical Sciences, University of Padua, I-35128 Padova (Italy); Istituto Oncologico Veneto, IOV-IRCCS, Padova (Italy); Rosato, Antonio [Department of Oncology and Surgical Sciences, University of Padua, I-35128 Padova (Italy); Istituto Oncologico Veneto, IOV-IRCCS, Padova (Italy)], E-mail: antonio.rosato@unipd.it

    2009-07-15

    Introduction: Gamma-ray detectors represent sensitive and noninvasive instruments to evaluate in vivo the metabolic trapping of radiopharmaceuticals. This study aimed to assess the imaging biodistribution of a [{sup 99m}Tc]-radiolabelled new prototype bioconjugate composed of paclitaxel linked to hyaluronan (ONCOFID-P). Methods: A small gamma camera providing high-resolution images was employed. Imaging of biodistribution following intravenous, intraperitoneal, intravesical and oral administration was carried out for a 2-h period in anesthetized mice receiving [{sup 99m}Tc]ONCOFID-P. At the end of the observation time, radioactivity in organs was directly measured. As a control, groups of mice were treated with free [{sup 3}H]paclitaxel given according to the same administration routes, and organ biodistribution of the drug was assessed after 2 h. Results: Intravenous inoculation of [{sup 99m}Tc]ONCOFID-P was followed by a rapid and strong liver uptake. In fact, almost 80% of the imaging signal was detected in this organ 10 min after injection and such value remained constant thereafter, thus indicating that the bioconjugate given through the intravenous route could be well suited to targeting primary or metastatic liver neoplasias. Imaging of the bladder, abdomen and gastrointestinal tract after local administration disclosed that the radiolabelled compound remained confined to the cavities, suggesting a potential regional application for transitional bladder cell carcinomas, ovarian cancers and gastric tumors, respectively. Free [{sup 3}H]paclitaxel biodistribution profoundly differed from that of [{sup 99m}Tc]ONCOFID-P. Conclusions: Conjugation of drugs with polymers results in new chemical entities characterized by a modified biodistribution pattern. Therefore, preclinical studies based on imaging analysis of such new compounds can suggest novel therapeutic applications.

  20. [Morphological and electrophysiological changes of the heart atria in necropsy patients with atrial fibrillation - a pilot study].

    Science.gov (United States)

    Matějková, Adéla; Steiner, Ivo

    2014-01-01

    Atrial fibrillation (AF), the most common supraventricular tachycardia, has a morphological base, so called remodelation of atrial myocardium, with its abnormal conduction pattern as a consequence. The remodelation regards electrical, contractile, and structural properties. In this pilot study we attempted to find relations between the myocardial morphological (scarring, amyloidosis, left atrial enlargement) and electrophysiological (ECG characteristics of the P-wave) changes in patients with AF. We examined 40 hearts of necropsy patients - 20 with a history of AF and 20 with no history of AF. Grossly, the heart weight and the size of the left atrium (LA) were evaluated. Histologically, 7 standard sites from the atria were examined. In each specimen, the degree of myocardial scarring and of deposition of isolated atrial amyloid (IAA) were assessed. We failed to show any significant difference in the P-wave pattern between patients with and without AF. Morphologically, however, there were several differences - the patients with AF had significantly heavier hearts, larger left atria, more severely scarred myocardium of the LA and the atrial septum, and more severe deposition of IAA in both atria in comparison to the control group of patients with sinus rhythm. The left atrial distribution of both fibrosis and amyloidosis was irregular. In patients with AF the former was most pronounced in the LA ceiling while the latter in the LA anterior wall. The entire series showed more marked amyloidosis in the left than in the right atrium. An interesting finding was the universal absence of IAA in the sinoatrial node. The knowledge of distribution of atrial myocardial structural changes could be utilized by pathologists in taking specimens for histology and also by cardiologists in targeting the radiofrequency ablation therapy.

  1. Alouatta trichromatic color vision: cone spectra and physiological responses studied with microspectrophotometry and single unit retinal electrophysiology.

    Science.gov (United States)

    Silveira, Luiz Carlos L; Saito, Cézar A; da Silva Filho, Manoel; Kremers, Jan; Bowmaker, James K; Lee, Barry B

    2014-01-01

    The howler monkeys (Alouatta sp.) are the only New World primates to exhibit routine trichromacy. Both males and females have three cone photopigments. However, in contrast to Old World monkeys, Alouatta has a locus control region upstream of each opsin gene on the X-chromosome and this might influence the retinal organization underlying its color vision. Post-mortem microspectrophotometry (MSP) was performed on the retinae of two male Alouatta to obtain rod and cone spectral sensitivities. The MSP data were consistent with only a single opsin being expressed in each cone and electrophysiological data were consistent with this primate expressing full trichromacy. To study the physiological organization of the retina underlying Alouatta trichromacy, we recorded from retinal ganglion cells of the same animals used for MSP measurements with a variety of achromatic and chromatic stimulus protocols. We found MC cells and PC cells in the Alouatta retina with similar properties to those previously found in the retina of other trichromatic primates. MC cells showed strong phasic responses to luminance changes and little response to chromatic pulses. PC cells showed strong tonic response to chromatic changes and small tonic response to luminance changes. Responses to other stimulus protocols (flicker photometry; changing the relative phase of red and green modulated lights; temporal modulation transfer functions) were also similar to those recorded in other trichromatic primates. MC cells also showed a pronounced frequency double response to chromatic modulation, and with luminance modulation response saturation accompanied by a phase advance between 10-20 Hz, characteristic of a contrast gain mechanism. This indicates a very similar retinal organization to Old-World monkeys. Cone-specific opsin expression in the presence of a locus control region for each opsin may call into question the hypothesis that this region exclusively controls opsin expression.

  2. An Electrophysiological Contribution to the Study of Language Lateralization and Prognosis of Aphasia

    Science.gov (United States)

    Cobianchi, Andrea

    2010-01-01

    The study is aimed at identifying hemispheric language dominance in both the right-handed and left-handed participants. Eighteen right-handed and 18 left-handed young volunteers were invited to listen for 80 times to a 720 ms duration Italian word. Signals from 16 electrodes were averaged and displayed both as traces and maps. When the word was…

  3. Emotional Reactivity, Regulation and Childhood Stuttering: A Behavioral and Electrophysiological Study

    Science.gov (United States)

    Arnold, Hayley S.; Conture, Edward G.; Key, Alexandra P. F.; Walden, Tedra

    2011-01-01

    The purpose of this preliminary study was to assess whether behavioral and psychophysiological correlates of emotional reactivity and regulation are associated with developmental stuttering, as well as determine the feasibility of these methods in preschool-age children. Nine preschool-age children who stutter (CWS) and nine preschool-age children…

  4. Morphological Family Size effects in L1 and L2 processing: An electrophysiological study

    NARCIS (Netherlands)

    Mulder, K.; Schreuder, R.; Dijkstra, A.F.J.

    2013-01-01

    The present study examined Morphological Family Size effects in first and second language processing. Items with a high or low Dutch (L1) Family Size were contrasted in four experiments involving Dutch–English bilinguals. In two experiments, reaction times (RTs) were collected in English (L2) and

  5. Visual electrophysiology in children

    Directory of Open Access Journals (Sweden)

    Jelka Brecelj

    2005-10-01

    Full Text Available Background: Electrophysiological assessment of vision in children helps to recognise abnormal development of the visual system when it is still susceptible to medication and eventual correction. Visual electrophysiology provides information about the function of the retina (retinal pigment epithelium, cone and rod receptors, bipolar, amacrine, and ganglion cells, optic nerve, chiasmal and postchiasmal visual pathway, and visual cortex.Methods: Electroretinograms (ERG and visual evoked potentials (VEP are recorded non-invasively; in infants are recorded simultaneously ERG with skin electrodes, while in older children separately ERG with HK loop electrode in accordance with ISCEV (International Society for Clinical Electrophysiology of Vision recommendations.Results: Clinical and electrophysiological changes in children with nystagmus, Leber’s congenital amaurosis, achromatopsia, congenital stationary night blindness, progressive retinal dystrophies, optic nerve hypoplasia, albinism, achiasmia, optic neuritis and visual pathway tumours are presented.Conclusions: Electrophysiological tests can help to indicate the nature and the location of dysfunction in unclear ophthalmological and/or neurological cases.

  6. Persistent Luminescence Nanophosphor Involved Near-Infrared Optical Bioimaging for Investigation of Foodborne Probiotics Biodistribution in Vivo: A Proof-of-Concept Study.

    Science.gov (United States)

    Liu, Yaoyao; Liu, Jing-Min; Zhang, Dongdong; Ge, Kun; Wang, Peihua; Liu, Huilin; Fang, Guozhen; Wang, Shuo

    2017-09-20

    Probiotics has attracted great attention in food nutrition and safety research field, but thus far there are limited analytical techniques for visualized and real-time monitoring of the probiotics when they are ingested in vivo. Herein, the optical bioimaging technique has been introduced for investigation of foodborne probiotics biodistribution in vivo, employing the near-infrared (NIR) emitting persistent luminescence nanophosphors (PLNPs) of Cr 3+ -doped zinc gallogermanate (ZGGO) as the contrast nanoprobes. The ultrabrightness, super long afterglow, polydispersed size, low toxicity, and excellent photostability and biocompatibility of PLNPs were demonstrated to be qualified as a tracer for labeling probiotics via antibody (anti-Gram positive bacteria LTA antibody) recognition as well as contrast agent for long-term bioimaging the probiotics. In vivo optical bioimaging assay showed that the LTA antibody functionalized ZGGO nanoprobes that could be efficiently tagged to the probiobics were successfully applied for real-time monitoring and nondamaged probing of the biodistribution of probiotics inside the living body after oral administration. This work presents a proof-of-concept that exploited the bioimaging methodology for real-time and nondamaged researching the foodborne probiotics behaviors in vivo, which would open up a novel way of food safety detection and nutrition investigation.

  7. Cognitive performance and electrophysiological indices of cognitive control: a validation study of conflict adaptation.

    Science.gov (United States)

    Clayson, Peter E; Larson, Michael J

    2012-05-01

    Psychiatric and neurologic disorders are associated with deficits in the postconflict recruitment of cognitive control. The primary aim of this study was to validate the relationship between cognitive functioning and indices of conflict adaptation. Event-related potentials were obtained from 89 healthy individuals who completed an Eriksen flanker task. Neuropsychological domains tested included memory, verbal fluency, and attention/executive functioning. Behavioral measures and N2 amplitudes showed significant conflict adaptation (i.e., previous-trial congruencies influenced current-trial measures). Higher scores on the attention/executive functioning and verbal fluency domains were associated with larger incongruent-trial N2 conflict adaptation; measures of cognitive functioning were not related to behavioral indices. This study provides initial validation of N2 conflict adaptation effects as cognitive function-related aspects of cognitive control. Copyright © 2012 Society for Psychophysiological Research.

  8. Electrophysiological study in the infraorbital nerve of the rat: Spontaneous and evoked activity

    Energy Technology Data Exchange (ETDEWEB)

    AlbarracIn, A L [Catedra de Neurociencias, Facultad de Medicina, Universidad Nacional de Tucuman, Av. Roca 2200, PC 4000 (Argentina); Farfan, F D [Departamento de BioingenierIa, FACET, Universidad Nacional de Tucuman, INSIBIO - CONICET, CC 327, PC 4000 (Argentina); Felice, C J [Departamento de BioingenierIa, FACET, Universidad Nacional de Tucuman, INSIBIO - CONICET, CC 327, PC 4000 (Argentina)

    2007-11-15

    In this work we present some studies in the afferent nerve of the rat vibrissae. Studies on spontaneous activity (SA) in this sensorial system are of long data. Nevertheless, SA recordings in the nerve of a single vibrissa have not been made until present. In this work, we use an algorithm based on signal decomposition with Continuous Wavelet Transform (CWT) to analyse the discharges of two nerves. The action potentials of both nerves were detected and the firing rates were calculated. These results suggest that the firing rate of one vibrissa innervation is low considering that this nerve contains hundred of fibers. In addition, we present preliminary studies suggesting important effects of the hair shaft length in the afferent discharge during the vibrissae movements. The experiments consisted in recording the nerve activity after the vibrissae were sectioned at two different levels. The results showed important differences in the signal energy contents. It suggests that the hair shaft length would produce a differential activation of the mechanoreceptors located in the vibrissae follicle.

  9. Effects of MRI on the electrophysiology of the motor cortex: a TMS study

    International Nuclear Information System (INIS)

    Schlamann, Marc; Pietrzyk, T.; Yoon, M.S.; Gerwig, M.; Kastrup, O.; Maderwald, S.; Forsting, M.; Ladd, S.C.; Duisburg-Essen Univ.; Bitz, A.; Ladd, M.E.

    2009-01-01

    The increasing spread of high-field and ultra-high-field MRI scanners encouraged a new discussion on safety aspects of MRI examinations. Earlier studies report altered acoustically evoked potentials. This finding was not able to be confirmed in later studies. In the present study transcranial magnetic stimulation (TMS) was used to evaluate whether motor cortical excitability may be altered following MRI examination even at field strength of 1.5 T. In 12 right-handed male volunteers individual thresholds for motor responses and then the length of the post-excitatory inhibition (silent period) were determined. Subsequently the volunteers were examined in the MRI scanner (Siemens Avanto, 1.5 T) for 63 minutes using gradient and spin echo sequences. MRI examination was immediately followed by another TMS session and a third 10 minutes later. As a control condition, the 12 subjects spent one hour in the scanner without examination and one hour on a couch without the presence of a scanner. After MRI examination, the silent period was significantly lengthened in all 12 subjects and then tended to the initial value after 10 min. Motor thresholds were significantly elevated and then normalized after 10 minutes. No significant effects were found in the control conditions. (orig.)

  10. Electrophysiological study in the infraorbital nerve of the rat: Spontaneous and evoked activity

    International Nuclear Information System (INIS)

    AlbarracIn, A L; Farfan, F D; Felice, C J

    2007-01-01

    In this work we present some studies in the afferent nerve of the rat vibrissae. Studies on spontaneous activity (SA) in this sensorial system are of long data. Nevertheless, SA recordings in the nerve of a single vibrissa have not been made until present. In this work, we use an algorithm based on signal decomposition with Continuous Wavelet Transform (CWT) to analyse the discharges of two nerves. The action potentials of both nerves were detected and the firing rates were calculated. These results suggest that the firing rate of one vibrissa innervation is low considering that this nerve contains hundred of fibers. In addition, we present preliminary studies suggesting important effects of the hair shaft length in the afferent discharge during the vibrissae movements. The experiments consisted in recording the nerve activity after the vibrissae were sectioned at two different levels. The results showed important differences in the signal energy contents. It suggests that the hair shaft length would produce a differential activation of the mechanoreceptors located in the vibrissae follicle

  11. Effect of anti-GM2 antibodies on rat sciatic nerve: electrophysiological and morphological study.

    Science.gov (United States)

    Ortiz, Nicolau; Sabaté, M Mar; Garcia, Neus; Santafe, Manel M; Lanuza, M Angel; Tomàs, Marta; Tomàs, Josep

    2009-03-31

    We found that a monoclonal human IgM anti-GM2 was fixed in rat sciatic axons and Schwann cells and was able to activate human complement. The passive transfer of IgM and complement in sciatic nerves can induce an acute alteration in nerve conduction. When the transfer of IgM plus complement was repeated for 10 days, the compound action motor potential amplitude was very low and the morphological study showed axons and myelin damage. Without human complement, IgM can only slightly disorganize the myelin by separating some layers, probably by interfering with the functional role of gangliosides in the myelin package.

  12. Ocular toxicity of beta-blockers and benzalkonium chloride in pigmented rabbits: electrophysiological and morphological studies.

    Science.gov (United States)

    Chou, A; Hori, S; Takase, M

    1985-01-01

    Subconjunctival injection of 0.2 ml of the following solutions was carried out once a day for two weeks in the albino and pigmented rabbit: commercial 0.5% timolol or 1% befunolol ophthalmic solutions, both containing benzalkonium chloride, and also these drug solutions containing no preservative, ophthalmic base solutions containing benzalkonium chloride, physiological saline solution or phosphate buffer solution. One week after daily injections of the commercial drug solutions or base solutions with benzalkonium chloride, the electroretinogram (ERG) showed a marked reduction in the a- and b-wave amplitudes in the pigmented rabbit, but the ERG changes were slight in the albino rabbit. After two weeks of injections, histological studies of the pigmented rabbit eyes revealed retinal detachment, visual cell loss and atrophy of the retinal pigment epithelium and choroid; the changes in the albino rabbit eyes were minimal. Injections of the beta-blockers containing no benzalkonium resulted in no significant changes in the ERG or in the tissue structures of all rabbits. Injections of only physiological saline or phosphate buffer had no deleterious effects. Therefore, the ocular toxicity of the beta-blockers was thought to be minor and the toxic effects seen in this study were thought to be due to benzalkonium chloride, which possibly accumulates in the ocular pigments.

  13. Cooperative context is a determinant of the social influence on outcome evaluation: An electrophysiological study.

    Science.gov (United States)

    Kimura, Kenta; Katayama, Jun'ichi

    2016-02-01

    The present study examined whether or not a cooperative context is a determinant of the social influence on the evaluation of two action outcomes: a monetary outcome and a conflict of opinion with other group members. In the present study, three-person groups were randomly assigned to be either a cooperative or individual group and asked to perform a gambling task. The monetary outcomes in the cooperative group were interrelated among group members, whereas those in the individual group did not influence each other. The present results showed that monetary outcomes elicited feedback-related negativity (FRN) and a conflict of opinion with other group members elicited FRN-like negativity, which reflect an evaluation of the motivational significance of action outcomes. The FRN elicited by monetary outcomes was reduced when participants shared decisions with other group members only in the cooperative group, indicating that the cooperative context reduced the motivational significance of monetary outcomes through the diffusion of responsibility. The FRN-like negativity elicited by a conflict of opinion showed a different pattern between the cooperative and individual groups, indicating that the cooperative context can influence the evaluation of a conflict of opinion, possibly via the modulation of group cohesiveness or conflict processing. The present results suggest that a cooperative context, rather than the social setting, is a determinant of the social influence on outcome evaluation. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Electrophysiological and MRI study on poor outcome after surgery for cervical myelopathy

    Energy Technology Data Exchange (ETDEWEB)

    Kameyama, Osamu; Kawakita, Hirofumi; Ogawa, Ryokei [Kansai Medical Univ., Moriguchi, Osaka (Japan)

    1995-11-01

    Occasionally, the outcome from laminoplasty for cervical spondylosis is disappointing despite an adequate operation. Before surgery, it is difficult to diagnose the pathological extent of the involvement of the spinal cord. The purpose of this study is to determine the efficacy of magnetic resonance imaging (MRI) and of the motor evoked potentials (MEPs) for the indication of the surgery and prognosis. Retrospectively, we investigated the MEPs and the MRI of 31 patients in surgery for cervical myelopathy, involving 21 with cervical spondylosis and 10 with ossification of the posterior longitudinal ligamentum, and compared the findings from those with a poor outcome (n=3l) with the findings from those with a good outcome (n=32). The MEPs from the thenar muscle and the tibialis anterior were evoked by transcranial magnetic brain stimulation. In the poor-outcome patients, the spinal canal was narrow and lumbar spinal canal stenosis was seen in 5 cases which required lumbar laminectomy. Before operation, the MEPs from the thenar muscle could not be evoked in 5 cases while there was a remarkably prolonged central motor conduction time in the other 26 cases. MRI revealed the deformed spinal cord in the involved area, and the signal intensity of the involved spinal cord in the T2 weighted image was remarkably high. The signal intensity ratio was significantly higher in the poor-outcome patients than in the good-outcome patients. This study suggested that a high signal intensity in the T2 weighted image and a prolonged conduction time or absence of MEPs largely corresponded to the clinical and other investigative features of myelopathy responsible for a poor outcome. (author).

  15. Electrophysiological and MRI study on poor outcome after surgery for cervical myelopathy

    International Nuclear Information System (INIS)

    Kameyama, Osamu; Kawakita, Hirofumi; Ogawa, Ryokei

    1995-01-01

    Occasionally, the outcome from laminoplasty for cervical spondylosis is disappointing despite an adequate operation. Before surgery, it is difficult to diagnose the pathological extent of the involvement of the spinal cord. The purpose of this study is to determine the efficacy of magnetic resonance imaging (MRI) and of the motor evoked potentials (MEPs) for the indication of the surgery and prognosis. Retrospectively, we investigated the MEPs and the MRI of 31 patients in surgery for cervical myelopathy, involving 21 with cervical spondylosis and 10 with ossification of the posterior longitudinal ligamentum, and compared the findings from those with a poor outcome (n=3l) with the findings from those with a good outcome (n=32). The MEPs from the thenar muscle and the tibialis anterior were evoked by transcranial magnetic brain stimulation. In the poor-outcome patients, the spinal canal was narrow and lumbar spinal canal stenosis was seen in 5 cases which required lumbar laminectomy. Before operation, the MEPs from the thenar muscle could not be evoked in 5 cases while there was a remarkably prolonged central motor conduction time in the other 26 cases. MRI revealed the deformed spinal cord in the involved area, and the signal intensity of the involved spinal cord in the T2 weighted image was remarkably high. The signal intensity ratio was significantly higher in the poor-outcome patients than in the good-outcome patients. This study suggested that a high signal intensity in the T2 weighted image and a prolonged conduction time or absence of MEPs largely corresponded to the clinical and other investigative features of myelopathy responsible for a poor outcome. (author)

  16. Bortezomib-induced painful peripheral neuropathy: an electrophysiological, behavioral, morphological and mechanistic study in the mouse.

    Directory of Open Access Journals (Sweden)

    Valentina A Carozzi

    Full Text Available Bortezomib is the first proteasome inhibitor with significant antineoplastic activity for the treatment of relapsed/refractory multiple myeloma as well as other hematological and solid neoplasms. Peripheral neurological complications manifesting with paresthesias, burning sensations, dysesthesias, numbness, sensory loss, reduced proprioception and vibratory sensitivity are among the major limiting side effects associated with bortezomib therapy. Although bortezomib-induced painful peripheral neuropathy is clinically easy to diagnose and reliable models are available, its pathophysiology remains partly unclear. In this study we used well-characterized immune-competent and immune-compromised mouse models of bortezomib-induced painful peripheral neuropathy. To characterize the drug-induced pathological changes in the peripheral nervous system, we examined the involvement of spinal cord neuronal function in the development of neuropathic pain and investigated the relevance of the immune response in painful peripheral neuropathy induced by bortezomib. We found that bortezomib treatment induced morphological changes in the spinal cord, dorsal roots, dorsal root ganglia (DRG and peripheral nerves. Neurophysiological abnormalities and specific functional alterations in Aδ and C fibers were also observed in peripheral nerve fibers. Mice developed mechanical allodynia and functional abnormalities of wide dynamic range neurons in the dorsal horn of spinal cord. Bortezomib induced increased expression of the neuronal stress marker activating transcription factor-3 in most DRG. Moreover, the immunodeficient animals treated with bortezomib developed a painful peripheral neuropathy with the same features observed in the immunocompetent mice. In conclusion, this study extends the knowledge of the sites of damage induced in the nervous system by bortezomib administration. Moreover, a selective functional vulnerability of peripheral nerve fiber subpopulations

  17. Biodistribution of N-isopropyl-p-iodoamphetamine

    International Nuclear Information System (INIS)

    Hoshi, Hiroaki; Jinnouchi, Seishi; Watanabe, Katsushi; Ueda, Takashi; Yamaguchi, Tadatoshi

    1987-01-01

    Biodistribution of N-isopropyl-p-iodoamphetamine (IMP) was experimentally studied for evaluating the usefullness of this radiopharmaceuticals for cerebral perfusion scintigraphy. IMP labeled with radioactive iodine (I-125, I-131), was injected intravenously in awake animals. The activity in the brain of male ddY mice injected 3.7 kBq (0.1 μCi) of I-125 IMP reached 8.0 (%Dose/g) at 10 min. after injection and it was almost constant till 120 min. Activity in the lung and heart was the highest just after injection, and rapidly decreased in the constant level lasting 30 min. to 120 min. Activity in the liver increased slowly and reached peak level at 60 min. Autoradiograms of male ddY mice injected 1.85 MBq (50 μCi) of I-131 IMP showed almost same activity in the spinal cord as the brain. Activities of I-131 IMP in normal brain of Sprague-Dawley rats injected 7.4 MBq (200 μCi) of I-131 IMP were 2.68 - 3.2 (%Dose/g) in the cerebral cortex and 0.59 - 0.66 (%Dose/g) in the white matter at 1 min. after injection. Activities in the cerebral cortex were slightly increased at 60 min. after injection and the activities in the white matter increased markedly at 60 min. and 6 hrs. after injection. The cerebral cortex to white matter ratios were about 5 at 1 min. or 10 min. and about 1 at 60 min. or 6 hrs. after injection. Autoradiograms of normal and ischemic rat brain showed local cerebral blood flow image, but the contrast between the gray matter and the white matter decreased at 60 min. or 6 hrs. Our study on the biodistribution of IMP showed the usefullness of this agent in cerebral perfusion imaging, and may be informative for the interpretation of images. (author)

  18. Age-dependent impairment of auditory processing under spatially focused and divided attention: an electrophysiological study.

    Science.gov (United States)

    Wild-Wall, Nele; Falkenstein, Michael

    2010-01-01

    By using event-related potentials (ERPs) the present study examines if age-related differences in preparation and processing especially emerge during divided attention. Binaurally presented auditory cues called for focused (valid and invalid) or divided attention to one or both ears. Responses were required to subsequent monaurally presented valid targets (vowels), but had to be suppressed to non-target vowels or invalidly cued vowels. Middle-aged participants were more impaired under divided attention than young ones, likely due to an age-related decline in preparatory attention following cues as was reflected in a decreased CNV. Under divided attention, target processing was increased in the middle-aged, likely reflecting compensatory effort to fulfill task requirements in the difficult condition. Additionally, middle-aged participants processed invalidly cued stimuli more intensely as was reflected by stimulus ERPs. The results suggest an age-related impairment in attentional preparation after auditory cues especially under divided attention and latent difficulties to suppress irrelevant information.

  19. Imagining the truth and the moon: an electrophysiological study of abstract and concrete word processing.

    Science.gov (United States)

    Gullick, Margaret M; Mitra, Priya; Coch, Donna

    2013-05-01

    Previous event-related potential studies have indicated that both a widespread N400 and an anterior N700 index differential processing of concrete and abstract words, but the nature of these components in relation to concreteness and imagery has been unclear. Here, we separated the effects of word concreteness and task demands on the N400 and N700 in a single word processing paradigm with a within-subjects, between-tasks design and carefully controlled word stimuli. The N400 was larger to concrete words than to abstract words, and larger in the visualization task condition than in the surface task condition, with no interaction. A marked anterior N700 was elicited only by concrete words in the visualization task condition, suggesting that this component indexes imagery. These findings are consistent with a revised or extended dual coding theory according to which concrete words benefit from greater activation in both verbal and imagistic systems. Copyright © 2013 Society for Psychophysiological Research.

  20. The effect of age on word-stem cued recall: a behavioral and electrophysiological study.

    Science.gov (United States)

    Osorio, Alexandra; Ballesteros, Soledad; Fay, Séverine; Pouthas, Viviane

    2009-09-15

    The present study investigated the effects of aging on behavioral cued-recall performance and on the neural correlates of explicit memory using event-related potentials (ERPs) under shallow and deep encoding conditions. At test, participants were required to complete old and new three-letter word stems using the letters as retrieval cues. The main results were as follows: (1) older participants exhibited the same level of explicit memory as young adults with the same high level of education. Moreover older adults benefited as much as young ones from deep processing at encoding; (2) brain activity at frontal sites showed that the shallow old/new effect developed and ended earlier for older than young adults. In contrast, the deep old/new effect started later for older than for young adults and was sustained up to 1000 ms in both age groups. Moreover, the results suggest that the frontal old/new effect was bilateral but greater over the right than the left electrode sites from 600 ms onward; (3) there were no differences at parietal sites between age groups: the old/new effect developed from 400 ms under both encoding conditions and was sustained up to 1000 ms under the deep condition but ended earlier (800 ms) under the shallow condition. These ERP results indicate significant age-related changes in brain activity associated with the voluntary retrieval of previously encoded information, in spite of similar behavioral performance of young and older adults.

  1. Epileptogenicity of cortical dysplasia in temporal lobe dual pathology: an electrophysiological study with invasive recordings.

    Science.gov (United States)

    Fauser, Susanne; Schulze-Bonhage, Andreas

    2006-01-01

    Hippocampal sclerosis is often associated with macroscopic or microscopic dysplasia in the temporal neocortex (TN). The relevance of such a dual pathology with regard to epileptogenesis is unclear. This study investigates the role of both pathologies in the generation of ictal and interictal activity. Ictal (113 seizures) and interictal data from invasive EEG recordings with simultaneous depth electrodes in the hippocampus and subdural electrodes over the TN were analysed retrospectively in 12 patients with variable degrees of hippocampal sclerosis and different types of histologically confirmed temporal cortical dysplasia [all male, age at epilepsy onset 25 Hz) and repetitive sharp waves. The interictal patterns over the TN were similar to those seen over extratemporal focal cortical dysplasias. Simultaneous recordings from the hippocampus and the TN strongly suggest that dysplastic tissue in the TN is often epileptogenic. The quantitative contribution of the hippocampus to seizure generation corresponded with the degree of hippocampal pathology, whereas different subtypes of cortical dysplasia did not affect its relative contribution to seizure generation and even mild forms of dysplasia were epileptogenic.

  2. Effect of Gallic Acid on Dementia Type of Alzheimer Disease in Rats: Electrophysiological and Histological Studies.

    Science.gov (United States)

    Hajipour, Somayeh; Sarkaki, Alireza; Farbood, Yaghoob; Eidi, Akram; Mortazavi, Pejman; Valizadeh, Zohreh

    2016-04-01

    To study the effect of gallic acid (GA) on hippocampal long-term potentiation (LTP) and histological changes in animal model of Alzheimer disease (AD) induced by beta-amyloid (Aβ). Sixty-four adult male Wistar rats (300±20 g) were divided into 8 groups: 1) Control (Cont); 2) AD; 3) Sham; 4-7) AD+GA (50, 100, and 200 mg/kg for 10 days, orally) or vehicle, 8) Cont+GA100, Aβ (1μg/μL in each site) was infused into hippocampus bilaterally. Changes of amplitude and slope of LTP induced in hippocampal dentate gyrus (DG) were evaluated by high frequency stimulation (HFS) of perforant path (PP). Data showed that LTP amplitude and area under curve significantly impaired in AD rats (P<0.001), while significantly improved in AD rats treated with GA (P<0.05, P<0.01). Current findings suggest that GA reduces neural damage and brain amyloid neuropathology and improves cognitive function via free radicals scavenging and inhibiting oligomerization of Aβ but with no effect on healthy rats.

  3. Electrophysiological Study of Algorithmically Processed Metric/Rhythmic Variations in Language and Music

    Directory of Open Access Journals (Sweden)

    Magne Cyrille

    2007-01-01

    Full Text Available This work is the result of an interdisciplinary collaboration between scientists from the fields of audio signal processing, phonetics and cognitive neuroscience aiming at studying the perception of modifications in meter, rhythm, semantics and harmony in language and music. A special time-stretching algorithm was developed to work with natural speech. In the language part, French sentences ending with tri-syllabic congruous or incongruous words, metrically modified or not, were made. In the music part, short melodies made of triplets, rhythmically and/or harmonically modified, were built. These stimuli were presented to a group of listeners that were asked to focus their attention either on meter/rhythm or semantics/harmony and to judge whether or not the sentences/melodies were acceptable. Language ERP analyses indicate that semantically incongruous words are processed independently of the subject's attention thus arguing for automatic semantic processing. In addition, metric incongruities seem to influence semantic processing. Music ERP analyses show that rhythmic incongruities are processed independently of attention, revealing automatic processing of rhythm in music.

  4. Electrophysiological Study of Algorithmically Processed Metric/Rhythmic Variations in Language and Music

    Directory of Open Access Journals (Sweden)

    Richard Kronland-Martinet

    2007-12-01

    Full Text Available This work is the result of an interdisciplinary collaboration between scientists from the fields of audio signal processing, phonetics and cognitive neuroscience aiming at studying the perception of modifications in meter, rhythm, semantics and harmony in language and music. A special time-stretching algorithm was developed to work with natural speech. In the language part, French sentences ending with tri-syllabic congruous or incongruous words, metrically modified or not, were made. In the music part, short melodies made of triplets, rhythmically and/or harmonically modified, were built. These stimuli were presented to a group of listeners that were asked to focus their attention either on meter/rhythm or semantics/harmony and to judge whether or not the sentences/melodies were acceptable. Language ERP analyses indicate that semantically incongruous words are processed independently of the subject's attention thus arguing for automatic semantic processing. In addition, metric incongruities seem to influence semantic processing. Music ERP analyses show that rhythmic incongruities are processed independently of attention, revealing automatic processing of rhythm in music.

  5. When early experiences build a wall to others' emotions: an electrophysiological and autonomic study.

    Directory of Open Access Journals (Sweden)

    Martina Ardizzi

    Full Text Available Facial expression of emotions is a powerful vehicle for communicating information about others' emotional states and it normally induces facial mimicry in the observers. The aim of this study was to investigate if early aversive experiences could interfere with emotion recognition, facial mimicry, and with the autonomic regulation of social behaviors. We conducted a facial emotion recognition task in a group of "street-boys" and in an age-matched control group. We recorded facial electromyography (EMG, a marker of facial mimicry, and respiratory sinus arrhythmia (RSA, an index of the recruitment of autonomic system promoting social behaviors and predisposition, in response to the observation of facial expressions of emotions. Results showed an over-attribution of anger, and reduced EMG responses during the observation of both positive and negative expressions only among street-boys. Street-boys also showed lower RSA after observation of facial expressions and ineffective RSA suppression during presentation of non-threatening expressions. Our findings suggest that early aversive experiences alter not only emotion recognition but also facial mimicry of emotions. These deficits affect the autonomic regulation of social behaviors inducing lower social predisposition after the visualization of facial expressions and an ineffective recruitment of defensive behavior in response to non-threatening expressions.

  6. The rat cochlea in the absence of circulating adrenal hormones: an electrophysiological and morphological study.

    Science.gov (United States)

    Lohuis, P J; Börjesson, P K; Klis, S F; Smoorenburg, G F

    2000-05-01

    Circulating adrenal hormones affect strial function. Removal of endogenous levels of adrenal steroids by bilateral adrenalectomy (ADX) in rats causes a decrease of Na(+)/K(+)-ATPase activity in the cochlear lateral wall [Rarey et al., 1989. Arch. Otolaryngol. Head Neck Surg. 115, 817-821] and a decrease of the volume of the marginal cells in the stria vascularis [Lohuis et al., 1990. Acta Otolaryngol. (Stockh.) 110, 348-356]. To study further the effect of absence of circulating adrenocorticosteroids on cochlear function, 18 male Long Evans rats underwent either an ADX or a SHAM operation. Electrocochleography was performed 1 week after surgery for tone bursts in a frequency range of 1-16 kHz. Thereafter, the cochleas were harvested and examined histologically. No significant changes in the amplitude growth curves of the summating potential (SP), the compound action potential (CAP) and the cochlear microphonics (CM) were detected after ADX. However, visually, there appeared to be a decrease of endolymphatic volume (tentatively called imdrops). Reissner's membrane (RM) extended less into scala vestibuli in ADX animals than in SHAM-operated animals. The ratio between the length of RM and the straight distance between the medial and lateral attachment points of RM were used as an objective measure to quantify this effect in each sub-apical half turn of the cochlea. The decrease in length of RM was statistically significant. Thus, circulating adrenal hormones appear to be necessary for normal cochlear fluid homeostasis. Absence of one or more of these hormones leads to shrinkage of the scala media (imdrops). However, the absence of adrenal hormones does not affect the gross cochlear potentials. Apparently, the cochlea is capable of compensating for the absence of circulating adrenal hormones to sustain the conditions necessary for proper cochlear transduction.

  7. Electrophysiological Studies into the Safety of the Anti-diarrheal Drug Clotrimazole during Oral Rehydration Therapy.

    Directory of Open Access Journals (Sweden)

    Willem S Lexmond

    2015-09-01

    Full Text Available Morbidity and mortality from acute diarrheal disease remains high, particularly in developing countries and in cases of natural or man-made disasters. Previous work has shown that the small molecule clotrimazole inhibits intestinal Cl- secretion by blocking both cyclic nucleotide- and Ca(2+-gated K(+ channels, implicating its use in the treatment of diarrhea of diverse etiologies. Clotrimazole, however, might also inhibit transporters that mediate the inwardly directed electrochemical potential for Na(+-dependent solute absorption, which would undermine its clinical application. Here we test this possibility by examining the effects of clotrimazole on Na(+-coupled glucose uptake.Short-circuit currents (Isc following administration of glucose and secretagogues were studied in clotrimazole-treated jejunal sections of mouse intestine mounted in Ussing chambers.Treatment of small intestinal tissue with clotrimazole inhibited the Cl- secretory currents that resulted from challenge with the cAMP-agonist vasoactive intestinal peptide (VIP or Ca(2+-agonist carbachol in a dose-dependent fashion. A dose of 30 μM was effective in significantly reducing the Isc response to VIP and carbachol by 50% and 72%, respectively. At this dose, uptake of glucose was only marginally affected (decreased by 14%, p = 0.37. There was no measurable effect on SGLT1-mediated sugar transport, as uptake of SGLT1-restricted 3-O-methyl glucose was equivalent between clotrimazole-treated and untreated tissue (98% vs. 100%, p = 0.90.Treatment of intestinal tissue with clotrimazole significantly reduced secretory responses caused by both cAMP- and Ca(2+-dependent agonists as expected, but did not affect Na(+-coupled glucose absorption. Clotrimazole could thus be used in conjunction with oral rehydration solution as a low-cost, auxiliary treatment of acute secretory diarrheas.

  8. Plasticity in the adult language system: a longitudinal electrophysiological study on second language learning.

    Science.gov (United States)

    Stein, M; Dierks, T; Brandeis, D; Wirth, M; Strik, W; Koenig, T

    2006-11-01

    Event-related potentials (ERPs) were used to trace changes in brain activity related to progress in second language learning. Twelve English-speaking exchange students learning German in Switzerland were recruited. ERPs to visually presented single words from the subjects' native language (English), second language (German) and an unknown language (Romansh) were measured before (day 1) and after (day 2) 5 months of intense German language learning. When comparing ERPs to German words from day 1 and day 2, we found topographic differences between 396 and 540 ms. These differences could be interpreted as a latency shift indicating faster processing of German words on day 2. Source analysis indicated that the topographic differences were accounted for by shorter activation of left inferior frontal gyrus (IFG) on day 2. In ERPs to English words, we found Global Field Power differences between 472 and 644 ms. This may due to memory traces related to English words being less easily activated on day 2. Alternatively, it might reflect the fact that--with German words becoming familiar on day 2--English words loose their oddball character and thus produce a weaker P300-like effect on day 2. In ERPs to Romansh words, no differences were observed. Our results reflect plasticity in the neuronal networks underlying second language acquisition. They indicate that with a higher level of second language proficiency, second language word processing is faster and requires shorter frontal activation. Thus, our results suggest that the reduced IFG activation found in previous fMRI studies might not reflect a generally lower activation but rather a shorter duration of activity.

  9. Evaluating Aesthetic Experience through Personal-Appearance Styles: A Behavioral and Electrophysiological Study

    Science.gov (United States)

    Cheung, Mei-chun; Law, Derry; Yip, Joanne

    2014-01-01

    Consumers' aesthetic experience has often been linked with the concept of beauty, which is regarded as subjective and may vary between individuals, cultures and places, and across time. With the advent of brain-imaging techniques, there is more and more evidence to suggest that aesthetic experience lies not only in the eye of the beholder, but also in the brain of the beholder. However, there are gaps in the previous research in this area, as several significant issues have not yet been addressed. Specifically, it is unclear whether the human brain really pays more attention and generates more positive emotional responses to beautiful things. To explore the brain activity relating to consumers' aesthetic experiences, 15 participants were recruited voluntarily to view a series of personal-appearance styles. They were invited to make aesthetic judgments while their brain activity was recorded by electroencephalography. Two electroencephalographic (EEG) indicators, theta coherence and frontal alpha symmetry, were utilized. Theta coherence is a measure of linear synchronization between signals at two electrode sites. It reflects the degree of functional cooperation between the underlying neuronal substrates and was used to explore the attentional processing involved in aesthetic judgments. Frontal alpha asymmetry is derived by subtracting the log-transformed absolute alpha power of the left hemisphere from the analogous log-transformed alpha power of the right hemisphere. It was used as an indicator of emotional response. During aesthetic judgments, long-range theta coherence increased in both hemispheres and more positive frontal alpha asymmetry was found when the styles were judged to be beautiful. Therefore, participants demonstrated brain activity suggestive of central executive processing and more positive emotional responses when they considered styles to be beautiful. The study provides some insight into the brain activity associated with consumers' aesthetic

  10. Evaluating aesthetic experience through personal-appearance styles: a behavioral and electrophysiological study.

    Directory of Open Access Journals (Sweden)

    Mei-chun Cheung

    Full Text Available Consumers' aesthetic experience has often been linked with the concept of beauty, which is regarded as subjective and may vary between individuals, cultures and places, and across time. With the advent of brain-imaging techniques, there is more and more evidence to suggest that aesthetic experience lies not only in the eye of the beholder, but also in the brain of the beholder. However, there are gaps in the previous research in this area, as several significant issues have not yet been addressed. Specifically, it is unclear whether the human brain really pays more attention and generates more positive emotional responses to beautiful things. To explore the brain activity relating to consumers' aesthetic experiences, 15 participants were recruited voluntarily to view a series of personal-appearance styles. They were invited to make aesthetic judgments while their brain activity was recorded by electroencephalography. Two electroencephalographic (EEG indicators, theta coherence and frontal alpha symmetry, were utilized. Theta coherence is a measure of linear synchronization between signals at two electrode sites. It reflects the degree of functional cooperation between the underlying neuronal substrates and was used to explore the attentional processing involved in aesthetic judgments. Frontal alpha asymmetry is derived by subtracting the log-transformed absolute alpha power of the left hemisphere from the analogous log-transformed alpha power of the right hemisphere. It was used as an indicator of emotional response. During aesthetic judgments, long-range theta coherence increased in both hemispheres and more positive frontal alpha asymmetry was found when the styles were judged to be beautiful. Therefore, participants demonstrated brain activity suggestive of central executive processing and more positive emotional responses when they considered styles to be beautiful. The study provides some insight into the brain activity associated with

  11. Evaluating aesthetic experience through personal-appearance styles: a behavioral and electrophysiological study.

    Science.gov (United States)

    Cheung, Mei-chun; Law, Derry; Yip, Joanne

    2014-01-01

    Consumers' aesthetic experience has often been linked with the concept of beauty, which is regarded as subjective and may vary between individuals, cultures and places, and across time. With the advent of brain-imaging techniques, there is more and more evidence to suggest that aesthetic experience lies not only in the eye of the beholder, but also in the brain of the beholder. However, there are gaps in the previous research in this area, as several significant issues have not yet been addressed. Specifically, it is unclear whether the human brain really pays more attention and generates more positive emotional responses to beautiful things. To explore the brain activity relating to consumers' aesthetic experiences, 15 participants were recruited voluntarily to view a series of personal-appearance styles. They were invited to make aesthetic judgments while their brain activity was recorded by electroencephalography. Two electroencephalographic (EEG) indicators, theta coherence and frontal alpha symmetry, were utilized. Theta coherence is a measure of linear synchronization between signals at two electrode sites. It reflects the degree of functional cooperation between the underlying neuronal substrates and was used to explore the attentional processing involved in aesthetic judgments. Frontal alpha asymmetry is derived by subtracting the log-transformed absolute alpha power of the left hemisphere from the analogous log-transformed alpha power of the right hemisphere. It was used as an indicator of emotional response. During aesthetic judgments, long-range theta coherence increased in both hemispheres and more positive frontal alpha asymmetry was found when the styles were judged to be beautiful. Therefore, participants demonstrated brain activity suggestive of central executive processing and more positive emotional responses when they considered styles to be beautiful. The study provides some insight into the brain activity associated with consumers' aesthetic

  12. An electrophysiological study of the impact of a Forward Collision Warning System in a simulator driving task.

    Science.gov (United States)

    Bueno, Mercedes; Fabrigoule, Colette; Deleurence, Philippe; Ndiaye, Daniel; Fort, Alexandra

    2012-08-27

    Driver distraction has been identified as the most important contributing factor in rear-end collisions. In this context, Forward Collision Warning Systems (FCWS) have been developed specifically to warn drivers of potential rear-end collisions. The main objective of this work is to evaluate the impact of a surrogate FCWS and of its reliability according to the driver's attentional state by recording both behavioral and electrophysiological data. Participants drove following a lead motorcycle in a simplified simulator with or without a warning system which gave forewarning of the preceding vehicle braking. Participants had to perform this driving task either alone (simple task) or simultaneously with a secondary cognitive task (dual task). Behavioral and electrophysiological data contributed to revealing a positive effect of the warning system. Participants were faster in detecting the brake light when the system was perfect or imperfect, and the time and attentional resources allocation required for processing the target at higher cognitive level were reduced when the system was completely reliable. When both tasks were performed simultaneously, warning effectiveness was considerably affected at both performance and neural levels; however, the analysis of the brain activity revealed fewer differences between distracted and undistracted drivers when using the warning system. These results show that electrophysiological data could be a valuable tool to complement behavioral data and to have a better understanding of how these systems impact the driver. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Electrophysiology Studies (EPS)

    Science.gov (United States)

    ... and Live Our Interactive Cardiovascular Library has detailed animations and illustrations to help you learn about conditions, treatments and procedures related to heart disease and stroke. Popular Articles 1 Understanding Blood Pressure Readings 2 Sodium and Salt 3 Heart Attack Symptoms ...

  14. An Electrophysiological Study

    African Journals Online (AJOL)

    of hypothyroidism are muscle weakness, fatigue, muscular and mental ... subclinical hypothyroid conditions.[8] ... median and sural nerves bilaterally in upper and lower limbs, .... and synthesis of proteins along with sensitivity of tissues.

  15. Intracardiac electrophysiology study (EPS)

    Science.gov (United States)

    ... rhythm Determine whether you are at risk for future heart events, especially sudden cardiac death See if ... patient with suspected arrhythmia. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: ...

  16. A Biodistribution and Toxicity Study of Cobalt Dichloride-N-Acetyl Cysteine in an Implantable MRI Marker for Prostate Cancer Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Frank, Steven J., E-mail: sjfrank@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Texas (United States); Johansen, Mary J. [Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Texas (United States); Martirosyan, Karen S. [Department of Physics and Astronomy, The University of Texas at Brownsville, Texas (United States); Gagea, Mihai; Van Pelt, Carolyn S.; Borne, Agatha [Department of Veterinary Medicine, Surgery, and Pathology, The University of Texas MD Anderson Cancer Center, Texas (United States); Carmazzi, Yudith; Madden, Timothy [Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Texas (United States)

    2013-03-15

    Purpose: C4, a cobalt dichloride-N-acetyl cysteine complex, is being developed as a positive-signal magnetic resonance imaging (MRI) marker to localize implanted radioactive seeds in prostate brachytherapy. We evaluated the toxicity and biodistribution of C4 in rats with the goal of simulating the systemic effects of potential leakage from C4 MRI markers within the prostate. Methods and Materials: 9-μL doses (equivalent to leakage from 120 markers in a human) of control solution (0.9% sodium chloride), 1% (proposed for clinical use), and 10% C4 solution were injected into the prostates of male Sprague-Dawley rats via laparotomy. Organ toxicity and cobalt disposition in plasma, tissues, feces, and urine were evaluated. Results: No C4-related morbidity or mortality was observed in the biodistribution arm (60 rats). Biodistribution was measurable after 10% C4 injection: cobalt was cleared rapidly from periprostatic tissue; mean concentrations in prostate were 163 μg/g and 268 μg/g at 5 and 30 minutes but were undetectable by 60 minutes. Expected dual renal-hepatic elimination was observed, with percentages of injected dose recovered in tissues of 39.0 ± 5.6% (liver), >11.8 ± 6.5% (prostate), and >5.3 ± 0.9% (kidney), with low plasma concentrations detected up to 1 hour (1.40 μg/mL at 5-60 minutes). Excretion in urine was 13.1 ± 4.6%, with 3.1 ± 0.54% recovered in feces by 24 hours. In the toxicity arm, 3 animals died in the control group and 1 each in the 1% and 10% groups from surgical or anesthesia-related complications; all others survived to scheduled termination at 14 days. No C4-related adverse clinical signs or organ toxicity were observed. Conclusion: C4-related toxicity was not observed at exposures at least 10-fold the exposure proposed for use in humans. These data demonstrating lack of systemic toxicity with dual routes of elimination in the event of in situ rupture suggest that C4 warrants further investigation as an MRI marker for prostate

  17. Biodistribution of 99mTc labelled anti TAG 72 chimeric McAb ccM4 in nude mice and preliminary clinical study

    International Nuclear Information System (INIS)

    Ma Qingjie; Zhao Jie; Zhang Yingnan; Gao Fengtong; Liu Shuqing

    1995-01-01

    Chimeric McAb ccM 4 was labelled with 99m Tc by direct method. The antibody was reduced by molar excess 2-mercaptoethanol (2-ME; Ab, 1000:1). The reduced ccM 4 chimeric McAb was mixed with 99m Tc reduced by SnCl 2 and 99m Tc labelling efficiency was 98%. The immunoreactivity did not change after labelling. The biodistribution of 99m Tc-ccM 4 was performed in nude mice and patients with stomach carcinoma. There was significantly more radioactivity in tumor than in the rest of the body in nude mice. Radioimmunoimaging of ccM 4 in 10 patients of gastric cancer was also presented

  18. Metabolic and Electrophysiological Changes Associated to Clinical Improvement in Two Severely Traumatized Subjects Treated With EMDR—A Pilot Study

    Directory of Open Access Journals (Sweden)

    Marco Pagani

    2018-04-01

    Full Text Available Neuroimaging represents a powerful tool to investigate the neurobiological correlates of Eye Movements Desensitization and Reprocessing (EMDR. The impact of EMDR on cortical and sub-cortical brain regions has been proven by several investigations demonstrating a clear association between symptoms disappearance and changes in cortical structure and functionality. The aim of this study was to assess by electroencephalography (EEG and for the first time by positron emission tomography (PET the changes occurring after EMDR therapy in two cases of psychological trauma following brain concussion and comatose state due to traffic accident. A 28 and a 29 years old men underwent extensive neuropsychological examination, which investigated: (i categorical and phonological verbal fluency; (ii episodic verbal memory; (iii executive functions; (iv visuospatial abilities; (v attention and working memory as well as clinical assessment by means of psychopathological tests (CAPS, IES, BDI, SCL90R, and DES. They were then treated by eight sessions of EMDR. During the first session EEG monitoring was continuously performed and 18F-FDG PET scans, depicting brain metabolism, were acquired at rest within a week (T0. After the last session, in which the two clients were considered to be symptoms-free, neuropsychological, clinical, and PET assessment were repeated (T1. PET data were semi-quantitatively compared to a group of 18 normal controls, as for EEG the preferential cortical activations were disclosed by thresholding the individual z-score to a p < 0.05. There was a significant improvement in clinical condition for both clients associated with a significant decrease in CAPS scores. IES and BDI were found to be pathological at T0 and improved at T1 in only one subject. Visuo-constructive abilities and abstract reasoning improved after EMDR in both subjects. As for EEG, the most striking changes occurred in fronto-temporal-parietal cortex in subject 1 while subject

  19. Biodistribution and radiation dosimetry of [18F]-5-fluorouracil

    International Nuclear Information System (INIS)

    Hino-Shishikura, Ayako; Suzuki, Akiko; Minamimoto, Ryogo; Shizukuishi, Kazuya; Oka, Takashi; Tateishi, Ukihide; Sugae, Sadatoshi; Ichikawa, Yasushi; Horiuchi, Choichi; Inoue, Tomio

    2013-01-01

    Purpose: To estimate the radiation dose and biodistribution of 18 F-5-fluorouracil ([ 18 F]-5-FU) from positron emission tomography/computed tomography (PET/CT) data, and to extrapolate mouse data to human data in order to evaluate cross-species consistency. Methods: Fifteen cancer patients (head and neck cancer (n=11), colon cancer (n=4)) were enrolled. Sequential PET/CT images were acquired for 2 h after intravenous administration of [ 18 F]-5-FU, and the percent of the injected dose delivered to each organ was derived. For comparison, [ 18 F]-5-FU was administered to female BALB/cAJcl-nu/nu nude mice (n=19), and the percent of the injected dose delivered to mouse organs was extrapolated to the human model. Absorbed radiation dose was calculated using OLINDA/EXM 1.0 software. Results: In human subjects, high [ 18 F]-5-FU uptake was seen in the liver, gallbladder and kidneys. The absorbed dose was highest in the gallbladder wall. In mice, the biodistribution of [ 18 F]-5-FU corresponded to that of humans. Estimated absorbed radiation doses for all organs were moderately correlated, and doses to organs (except the gallbladder and urinary bladder) were significantly correlated between mice and humans. The mean effective [ 18 F]-5-FU dose was higher in humans (0.0124 mSv/MBq) than in mice (0.0058 mSv/MBq). Conclusion: Biodistribution and radiation dosimetry of [ 18 F]-5-FU were compared between humans and mice: biodistribution in mice and humans was similar. Data from mice underestimated the effective dose in humans, suggesting that clinical measurements are needed for more detailed dose estimation in order to ensure radiation safety. The observed effective doses suggest the feasibility of [ 18 F]-5-FU PET/CT for human studies. - Highlights: ► The radiation dose and biodistribution of [ 18 F]-5-FU were estimated from mouse and human data. ► The biodistribution of [ 18 F]-5-FU of mouse and human was corresponded. ► Estimated absorbed radiation doses for organs

  20. Comprehensive characterizations of nanoparticle biodistribution following systemic injection in mice

    Science.gov (United States)

    Liao, Wei-Yin; Li, Hui-Jing; Chang, Ming-Yao; Tang, Alan C. L.; Hoffman, Allan S.; Hsieh, Patrick C. H.

    2013-10-01

    Various nanoparticle (NP) properties such as shape and surface charge have been studied in an attempt to enhance the efficacy of NPs in biomedical applications. When trying to undermine the precise biodistribution of NPs within the target organs, the analytical method becomes the determining factor in measuring the precise quantity of distributed NPs. High performance liquid chromatography (HPLC) represents a more powerful tool in quantifying NP biodistribution compared to conventional analytical methods such as an in vivo imaging system (IVIS). This, in part, is due to better curve linearity offered by HPLC than IVIS. Furthermore, HPLC enables us to fully analyze each gram of NPs present in the organs without compromising the signals and the depth-related sensitivity as is the case in IVIS measurements. In addition, we found that changing physiological conditions improved large NP (200-500 nm) distribution in brain tissue. These results reveal the importance of selecting analytic tools and physiological environment when characterizing NP biodistribution for future nanoscale toxicology, therapeutics and diagnostics.Various nanoparticle (NP) properties such as shape and surface charge have been studied in an attempt to enhance the efficacy of NPs in biomedical applications. When trying to undermine the precise biodistribution of NPs within the target organs, the analytical method becomes the determining factor in measuring the precise quantity of distributed NPs. High performance liquid chromatography (HPLC) represents a more powerful tool in quantifying NP biodistribution compared to conventional analytical methods such as an in vivo imaging system (IVIS). This, in part, is due to better curve linearity offered by HPLC than IVIS. Furthermore, HPLC enables us to fully analyze each gram of NPs present in the organs without compromising the signals and the depth-related sensitivity as is the case in IVIS measurements. In addition, we found that changing physiological

  1. Anti-CEA aptamers labeled with {sup 99m}Tc: encapsulation studies in long-circulating and pH-sensitive liposomes, biodistribution and imaging

    Energy Technology Data Exchange (ETDEWEB)

    Leonel, M.F.V.; Andrade, A.S.R. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Oliveira, M.C.; Cardoso, V.N.; Barros, A.L.B. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Farmacia

    2015-07-01

    Colorectal cancer (CRC) is one of the leading cancers and the carcinoembryonic antigen (CEA) is a tumor marker widely used in diagnosis since it is overexpressed in tumor cells. Acid nucleic aptamers with high affinity and specificity for this antigen become promising molecules for CRC diagnosis by imaging. However, due to the action of nucleases in vivo, they have been investigated for association with liposomes, such as long-circulating and pH-sensitive liposomes (SPHL) that can be destabilized in the tumor region releasing aptamers and contributing to the CRC diagnosis by scintigraphy. In this work, SpHL containing DOPE, CHEMS and mPEG{sub 2000}-DSPE were characterized by analyzing mean diameter, polydispersity index and zeta potential. The anti-CEA aptamers Apt3 and Apt3-Amino were labeled with technetium-99m and the encapsulation efficiency (EE) of {sup 99m}Tc-Apt3 in the SpHL by dehydration-rehydration (modified DRV) and freeze-thaw (FT) were analyzed, both in the presence of cryoprotectants. Biodistribution and scintigraphic images were performed at 1h and 4h post-injection of {sup 99m}Tc-Apt3-amino, {sup 99m}Tc-Apt3-SpHL or {sup 99m}Tc-Apt3-amino-SpHL complexes in Balb/c healthy mice. The SpHL dispersions were homogeneous. The radiolabeling yield with technetium-99m was over 90% for all complexes. By the dehydration-rehydration method, the SpHL increased over 200% after encapsulation procedure. By the freeze-thaw method, the SpHL size increased only 13.7%. Free {sup 99m}Tc-Apt3-amino showed to be cleared by renal via with high levels of radioactivity in the kidney and bladder, however, the {sup 99m}Tc-Apt3-SpHL and {sup 99m}Tc-Apt3-amino-SpHL clearly indicated high uptake by liver and spleen. The biodistribution of {sup 99m}Tc-Apt3-SpHL showed significant uptake of radioactivity by stomach and thyroid indicating less stability of the Apt3 radiolabelling in relation to Apt3-amino. (author)

  2. Anti-CEA aptamers labeled with 99mTc: encapsulation studies in long-circulating and pH-sensitive liposomes, biodistribution and imaging

    International Nuclear Information System (INIS)

    Leonel, M.F.V.; Andrade, A.S.R.; Oliveira, M.C.; Cardoso, V.N.; Barros, A.L.B.

    2015-01-01

    Colorectal cancer (CRC) is one of the leading cancers and the carcinoembryonic antigen (CEA) is a tumor marker widely used in diagnosis since it is overexpressed in tumor cells. Acid nucleic aptamers with high affinity and specificity for this antigen become promising molecules for CRC diagnosis by imaging. However, due to the action of nucleases in vivo, they have been investigated for association with liposomes, such as long-circulating and pH-sensitive liposomes (SPHL) that can be destabilized in the tumor region releasing aptamers and contributing to the CRC diagnosis by scintigraphy. In this work, SpHL containing DOPE, CHEMS and mPEG 2000 -DSPE were characterized by analyzing mean diameter, polydispersity index and zeta potential. The anti-CEA aptamers Apt3 and Apt3-Amino were labeled with technetium-99m and the encapsulation efficiency (EE) of 99m Tc-Apt3 in the SpHL by dehydration-rehydration (modified DRV) and freeze-thaw (FT) were analyzed, both in the presence of cryoprotectants. Biodistribution and scintigraphic images were performed at 1h and 4h post-injection of 99m Tc-Apt3-amino, 99m Tc-Apt3-SpHL or 99m Tc-Apt3-amino-SpHL complexes in Balb/c healthy mice. The SpHL dispersions were homogeneous. The radiolabeling yield with technetium-99m was over 90% for all complexes. By the dehydration-rehydration method, the SpHL increased over 200% after encapsulation procedure. By the freeze-thaw method, the SpHL size increased only 13.7%. Free 99m Tc-Apt3-amino showed to be cleared by renal via with high levels of radioactivity in the kidney and bladder, however, the 99m Tc-Apt3-SpHL and 99m Tc-Apt3-amino-SpHL clearly indicated high uptake by liver and spleen. The biodistribution of 99m Tc-Apt3-SpHL showed significant uptake of radioactivity by stomach and thyroid indicating less stability of the Apt3 radiolabelling in relation to Apt3-amino. (author)

  3. Biodistribution of gyroxin using 125I as radiotracer

    International Nuclear Information System (INIS)

    Alves da Silva, J.A.; Ribela, M.T.C.P.; Rogero, J.R.; Camillo, M.A.P.; Muramoto, E.

    2006-01-01

    The use of radiotracers in the research of animal venom has been scarce, although it allows an excellent approach to follow the process of bioavailability, biodistribution and kinetics of toxins. The purpose of this study was to assess gyroxin action mechanism, transport, compartments and action sites. This toxin is a thrombin-like and causes the barrel rotation syndrome. The gyroxin was labeled with 125 I and used as a tracer for the in vivo assay in mice. Blood samples and organs were collected at different time intervals, weighed and analyzed in a gamma-counter. The data was related with tissues distribution of protease activated receptor (PAR). Biodistribution assay allowed dividing the organs into three groups. The first one with the organs that followed the blood kinetics, the second with the organs related to metabolisms and elimination, and the third with the organs in which the gyroxin concentration increased during the observation period. (author)

  4. Study of biodistribution of lipidic nanospheres charged with cis-diaminedichloroplatinum (II) and labelled with radioactive nuclei of Indium-111; Estudio de biodistribucion de nanoesferas lipidicas cargadas con cis-diaminodicloroplatino (II) y marcadas con nucleos radioactivos de Indio-111

    Energy Technology Data Exchange (ETDEWEB)

    Lopez R, V.; Juarez O, C.; Medina L, A. [Unidad de Investigacion Biomedica en Cancer INCAN-UNAM, Mexico D.F. (Mexico); Perez C, E.; Garcia L, P. [Instituto nacional de cancerologia, Mexico D.F. (Mexico)

    2007-07-01

    The general objective of the study was to evaluate the lipidic nanospheres biodistribution charged with cis-diaminedichloroplatinum (II) (cis-DDP) and labelled with radioactive nuclei of Indium-111 (Lip-Cis-in-111) in Wistar rats and in a tumoral model of CaCu. The conclusions were: 1. The system Lip-Cis-in-111 it presents a very fast elimination probably, to a fast recognition response of the reticuloendothelial system (RES). 2. It is planned to make modifications to the formulation to increase the quantity of the hydrophilic polymer (PEG), so that its time of residence in the blood is bigger and allow a bigger accumulation in the tumor. (Author)

  5. Preclinical pharmacokinetics, biodistribution, radiation dosimetry and acute toxicity studies required for regulatory approval of a Clinical Trial Application for a Phase I/II clinical trial of 111In-BzDTPA-pertuzumab

    International Nuclear Information System (INIS)

    Lam, Karen; Chan, Conrad; Done, Susan J.; Levine, Mark N.; Reilly, Raymond M.

    2015-01-01

    Introduction: 111 In-BzDTPA-pertuzumab is a novel imaging probe for detecting changes in HER2 expression in breast cancer (BC) caused by treatment with trastuzumab (Herceptin). Our aim was to evaluate the pharmacokinetics, normal tissue biodistribution, radiation dosimetry and acute toxicity of 111 In-BzDTPA-pertuzumab in non-tumor bearing mice in order to obtain regulatory approval to advance this agent to a first-in-humans Phase I/II clinical trial. Methods: Biodistribution and pharmacokinetic studies were performed in non-tumor bearing Balb/c mice injected i.v. with 111 In-BzDTPA-pertuzumab (2.5 MBq; 2 μg). The cumulative number of disintegrations per source organ derived from the biodistribution data was used to predict the radiation absorbed doses in humans using OLINDA/EXM software. Acute toxicity was studied at two weeks post-injection of 111 In-BzDTPA-pertuzumab (1.0 MBq, 20 μg) with comparison to control mice injected with unlabeled BzDTPA-pertuzumab (20 μg) or Sodium Chloride Injection USP. The dose of 111 In-BzDTPA-pertuzumab corresponded to 23-times the human radioactivity dose and 10-times the protein dose on a MBq/kg and mg/kg basis, respectively. Toxicity was assessed by monitoring body mass, complete blood cell count (CBC), hematocrit (Hct), hemoglobin (Hb), serum creatinine (SCr) and alanine aminotransferease (ALT) and by histopathological examination of tissues at necropsy. Results: 111 In-BzDTPA-pertuzumab exhibited a biphasic elimination from the blood with a distribution half-life (t 1/2 α) of 3.8 h and an elimination half-life (t 1/2 β) of 228.2 h. The radiopharmaceutical was distributed mainly in the blood, heart, lungs, liver, kidneys and spleen. The projected whole-body radiation absorbed dose in humans was 0.05 mSv/MBq corresponding to a total of 16.8 mSv for three separate administrations of 111 In-BzDTPA-pertuzumab (111 MBq) planned for the Phase I/II trial. There were slight changes in Hb and SCr levels associated with

  6. Hemodynamic and electrophysiological signals of conflict processing in the Chinese-character Stroop task: a simultaneous near-infrared spectroscopy and event-related potential study.

    Science.gov (United States)

    Zhai, Jiahuan; Li, Ting; Zhang, Zhongxing; Gong, Hui

    2009-01-01

    A dual-modality method combining continuous-wave near-infrared spectroscopy (NIRS) and event-related potentials (ERPs) was developed for the Chinese-character color-word Stroop task, which included congruent, incongruent, and neutral stimuli. Sixteen native Chinese speakers participated in this study. Hemodynamic and electrophysiological signals in the prefrontal cortex (PFC) were monitored simultaneously by NIRS and ERP. The hemodynamic signals were represented by relative changes in oxy-, deoxy-, and total hemoglobin concentration, whereas the electrophysiological signals were characterized by the parameters P450, N500, and P600. Both types of signals measured at four regions of the PFC were analyzed and compared spatially and temporally among the three different stimuli. We found that P600 signals correlated significantly with the hemodynamic parameters, suggesting that the PFC executes conflict-solving function. Additionally, we observed that the change in deoxy-Hb concentration showed higher sensitivity in response to the Stroop task than other hemodynamic signals. Correlation between NIRS and ERP signals revealed that the vascular response reflects the cumulative effect of neural activities. Taken together, our findings demonstrate that this new dual-modality method is a useful approach to obtaining more information during cognitive and physiological studies.

  7. Risk of malignant arrhythmias in initially symptomatic patients with Wolff-Parkinson-White syndrome: results of a prospective long-term electrophysiological follow-up study.

    Science.gov (United States)

    Pappone, Carlo; Vicedomini, Gabriele; Manguso, Francesco; Baldi, Mario; Pappone, Alessia; Petretta, Andrea; Vitale, Raffaele; Saviano, Massimo; Ciaccio, Cristiano; Giannelli, Luigi; Calovic, Zarko; Tavazzi, Luigi; Santinelli, Vincenzo

    2012-02-07

    The available amount of detailed long-term data in patients with Wolff-Parkinson-White syndrome is limited, and no prospective electrophysiological studies looking at predictors of malignant arrhythmia are available. Among 8575 symptomatic Wolff-Parkinson-White patients with atrioventricular reentrant tachycardia referred for electrophysiological test, 369 (mean age, 23±12.5 years) declined catheter ablation and were followed up. The primary end point of the study was to evaluate over a 5-year follow-up the predictors and characteristics of patients who develop malignant arrhythmias. After a mean follow-up of 42.1±10 months, malignant arrhythmias developed in 29 patients (mean age, 13.9±5.6 years; 26 male), resulting in presyncope/syncope (25 patients), hemodynamic collapse (3 patients), or cardiac arrest caused by ventricular fibrillation (1 patient). Of the remaining 340 patients, 168 (mean age, 34.2±9.0 years) remained asymptomatic up to 5 years, and 172 (mean age, 13.6±5.1 years) had benign recurrence, including sustained atrioventricular reentrant tachycardia (132 patients) or atrial fibrillation (40 patients). Compared with the group with no malignant arrhythmias, the group with malignant arrhythmias showed shorter accessory-pathway effective refractory period (PWolff-Parkinson-White syndrome generally have a good outcome, and predictors of malignant arrhythmias are similar to those reported for asymptomatic patients with ventricular pre-excitation.

  8. Biodistribution of Different Sized Nanodiamonds in Mice.

    Science.gov (United States)

    Purtov, Konstantin; Petunin, Alexey; Inzhevatkin, Evgeny; Burov, Andrey; Ronzhin, Nikita; Puzyr, Alexey; Bondar, Vladimir

    2015-02-01

    The particle size is one of critical parameters influencing the biodistribution of detonation nanodiamonds (DND) after their administration into the body. As DNDs are prone to aggregation, the difference between their sizes in aqueous and physiological solutions has to be taken into account. Radioactive I125-BSA molecules were covalently immobilized on DNDs divided in three fractions of different average size. The DND-BSAI125 conjugates were intravenously administrated into adult mice and the particle allocation in the animal's organs and blood was evaluated based on the radioactivity distribution. We conclude that most of the conjugates were taken from the bloodstream and trapped in the liver and spleen. The short-term distribution pattern for all DNDs was similar regardless of size and practically unchanged with time. No significant clearance of the particles was observed for 4 h, but the presence of DNDs was detected in the blood. It was found that the largest particles tend to accumulate more into the liver as compared to the smaller ones. However, the size effect was not well pronounced for the studied size range.

  9. Clinical, electrophysiological, and prognostic study of postinjection sciatic nerve injury: An avoidable cause of loss of limb in the peripheral medical service

    Directory of Open Access Journals (Sweden)

    Wani Maqbool

    2009-01-01

    Full Text Available Background: Post injection sciatic nerve injury is a common cause of sciatic nerve mononeuropathy in the developing world largely due to inadequate health care facilites in the rural regions. Objective: The study was conducted to analyse the pattern of this nerve lesion in clinical and electrophysiological parameters and also to study the outcome in a conservatively treated cohort. Materials and Methods: One hundred and six patients who underwent evaluation at our laboratory from 2000 to 2006 for post injection sciatic neuropathy formed the study population. Twenty two of these were followed up (mean 6.6 months for the outcome. Results: In the cases with full data, common peroneal division of the sciatic nerve was affected alone or predominantly. On follow up, 72% cases showed little or partial recovery. Thirty two percent patients had residual trophic changes and causalgia at their last visit. Conclusion: The majority of cases of postinjection sciatic nerve injury have poor prognosis on conservative treatment.

  10. Noninvasive optical imaging of nanomedicine biodistribution

    Czech Academy of Sciences Publication Activity Database

    Kunjachan, S.; Gremse, F.; Theek, B.; Koczera, P.; Pola, Robert; Pechar, Michal; Etrych, Tomáš; Ulbrich, Karel; Storm, G.; Kiessling, F.; Lammers, T.

    2013-01-01

    Roč. 7, č. 1 (2013), s. 252-262 ISSN 1936-0851 R&D Projects: GA ČR GAP301/11/0325 Institutional research plan: CEZ:AV0Z40500505 Institutional support: RVO:61389013 Keywords : nanomedicine * drug targeting * biodistribution Subject RIV: CD - Macromolecular Chemistry Impact factor: 12.033, year: 2013

  11. Biodistribution of Carbon Nanotubes in Animal Models

    DEFF Research Database (Denmark)

    Jacobsen, Nicklas Raun; Møller, Peter Horn; Clausen, Per Axel

    2017-01-01

    The many interesting physical and chemical properties of carbon nanotubes (CNT) make it one of the most commercially attractive materials in the era of nanotechnology. Here, we review the recent publications on in vivo biodistribution of pristine and functionalized forms of single-walled and multi...

  12. A Clinical and Electrophysiological Study of Peripheral Neuropathies in Predialysis Chronic Kidney Disease Patients and Relation of Severity of Peripheral Neuropathy with Degree of Renal Failure.

    Science.gov (United States)

    Jasti, Dushyanth Babu; Mallipeddi, Sarat; Apparao, A; Vengamma, B; Sivakumar, V; Kolli, Satyarao

    2017-01-01

    To study the prevalence, clinical features, electrophysiological features, and severity of peripheral neuropathy in predialysis chronic kidney disease (CKD) patients with respect to severity of renal failure and presence of diabetes mellitus. Between May 2015 and December 2016, 200 predialysis CKD patients were assessed prospectively. The prevalence of peripheral neuropathy in predialysis CKD patients in the present study was 45% based on clinical symptoms and 90% electrophysiologically. Mean age of 200 predialysis CKD patients who participated in the study was 53.2 ± 13.2 years. One hundred and thirty-six (68%) patients were male and 64 (32%) patients were female. Mean duration of disease was 2.2 ± 1.6 years. Nearly 45% patients of patients had asymptomatic peripheral neuropathy in the present study, which was more common in mild-to-moderate renal failure group. One hundred twenty-six patients (63%) had definite damage and 54 patients (27%) had early damage. In mild-to-moderate renal failure ( n = 100) and severe renal failure patients ( n = 100), 88% and 92% had significant peripheral neuropathy, respectively. Most common nerves involved were sural nerve, median sensory nerve, and ulnar sensory nerve. Diabetic patients (97%) showed more severe and high prevalence of peripheral neuropathy when compared to nondiabetic patients (83%). Most common patterns were pure axonal sensorimotor neuropathy and mixed sensorimotor neuropathy. Peripheral neuropathy is common in predialysis patients, prevalence and severity of which increases as renal failure worsens. Predialysis patients with diabetes show higher prevalence and severity of peripheral neuropathy when compared with nondiabetics.

  13. A Clinical and Electrophysiological Study of Peripheral Neuropathies in Predialysis Chronic Kidney Disease Patients and Relation of Severity of Peripheral Neuropathy with Degree of Renal Failure

    Science.gov (United States)

    Jasti, Dushyanth Babu; Mallipeddi, Sarat; Apparao, A.; Vengamma, B.; Sivakumar, V.; Kolli, Satyarao

    2017-01-01

    Objective: To study the prevalence, clinical features, electrophysiological features, and severity of peripheral neuropathy in predialysis chronic kidney disease (CKD) patients with respect to severity of renal failure and presence of diabetes mellitus. Materials and Methods: Between May 2015 and December 2016, 200 predialysis CKD patients were assessed prospectively. Results: The prevalence of peripheral neuropathy in predialysis CKD patients in the present study was 45% based on clinical symptoms and 90% electrophysiologically. Mean age of 200 predialysis CKD patients who participated in the study was 53.2 ± 13.2 years. One hundred and thirty-six (68%) patients were male and 64 (32%) patients were female. Mean duration of disease was 2.2 ± 1.6 years. Nearly 45% patients of patients had asymptomatic peripheral neuropathy in the present study, which was more common in mild-to-moderate renal failure group. One hundred twenty-six patients (63%) had definite damage and 54 patients (27%) had early damage. In mild-to-moderate renal failure (n = 100) and severe renal failure patients (n = 100), 88% and 92% had significant peripheral neuropathy, respectively. Most common nerves involved were sural nerve, median sensory nerve, and ulnar sensory nerve. Diabetic patients (97%) showed more severe and high prevalence of peripheral neuropathy when compared to nondiabetic patients (83%). Most common patterns were pure axonal sensorimotor neuropathy and mixed sensorimotor neuropathy. Conclusion: Peripheral neuropathy is common in predialysis patients, prevalence and severity of which increases as renal failure worsens. Predialysis patients with diabetes show higher prevalence and severity of peripheral neuropathy when compared with nondiabetics. PMID:29204008

  14. Electrophysiological studies of salty taste modification by organic acids in the labellar taste cell of the blowfly.

    Science.gov (United States)

    Murata, Yoshihiro; Kataoka-Shirasugi, Naoko; Amakawa, Taisaku

    2002-01-01

    Using the labellar salt receptor cells of the blowfly, Phormia regina, we electrophysiologically showed that the response to NaCl and KCl aqueous solutions was enhanced and depressed by acetic, succinic and citric acids. The organic acid concentrations at which the most enhanced salt response (MESR) was obtained were found to be different: 0.05-1 mM citric acid, 0.5-2 mM succinic acid and 5-50 mM acetic acid. Moreover, the degree of the salt response was not always dependent on the pH values of the stimulating solutions. The salt response was also enhanced by HCl (pH 3.5-3.0) only when the NaCl concentration was greater than the threshold, indicating that the salty taste would be enhanced by the comparatively lower concentrations of hydrogen ions. Another explanation for the enhancement is that the salty taste may also be enhanced by undissociated molecules of the organic acids, because the MESRs were obtained at the pH values lower than the pKa(1) or pKa(2) values of these organic acids. On the other hand, the salty taste could be depressed by both the lower pH range (pH 2.5-2.0) and the dissociated organic anions from organic acid molecules with at least two carboxyl groups.

  15. Magnetic resonance imaging guided transatrial electrophysiological studies in swine using active catheter tracking - experience with 14 cases

    Energy Technology Data Exchange (ETDEWEB)

    Grothoff, Matthias; Gutberlet, Matthias [University of Leipzig - Heart Center, Department of Radiology, Leipzig (Germany); Hindricks, Gerhard; Sommer, Philipp; Hilbert, Sebastian [University of Leipzig - Heart Center, Department of Electrophysiology, Leipzig (Germany); Fleiter, Christian [Helios Klinikum Berlin-Buch, Department of Orthopaedic Surgery, Berlin (Germany); Schnackenburg, Bernhard [Philips Healthcare, Hamburg (Germany); Weiss, Steffen; Krueger, Sascha [Philips Innovative Technologies, Hamburg (Germany); Piorkowski, Christopher; Gaspar, Thomas [University of Dresden - Heart Center, Department of Electrophysiology, Dresden (Germany); Wedan, Steve; Lloyd, Thomas [Imricor Medical Systems, Burnsville, MN (United States)

    2017-05-15

    To evaluate the feasibility of performing comprehensive Cardiac Magnetic resonance (CMR) guided electrophysiological (EP) interventions in a porcine model encompassing left atrial access. After introduction of two femoral sheaths 14 swine (41 ± 3.6 kg) were transferred to a 1.5 T MR scanner. A three-dimensional whole-heart sequence was acquired followed by segmentation and the visualization of all heart chambers using an image-guidance platform. Two MR conditional catheters were inserted. The interventional protocol consisted of intubation of the coronary sinus, activation mapping, transseptal left atrial access (n = 4), generation of ablation lesions and eventually ablation of the atrioventricular (AV) node. For visualization of the catheter tip active tracking was used. Catheter positions were confirmed by passive real-time imaging. Total procedure time was 169 ± 51 minutes. The protocol could be completed in 12 swine. Two swine died from AV-ablation induced ventricular fibrillation. Catheters could be visualized and navigated under active tracking almost exclusively. The position of the catheter tips as visualized by active tracking could reliably be confirmed with passive catheter imaging. Comprehensive CMR-guided EP interventions including left atrial access are feasible in swine using active catheter tracking. (orig.)

  16. Detection of sites of infection in mice using 99mTc-labeled PN2S-PEG conjugated to UBI and 99mTc-UBI: a comparative biodistribution study

    International Nuclear Information System (INIS)

    Melendez-Alafort, Laura; Nadali, Anna; Pasut, Gianfranco; Zangoni, Elena; De Caro, Raffaele; Cariolato, Luca; Giron, Maria Cecilia; Castagliuolo, Ignazio; Veronese, Francesco M.; Mazzi, Ulderico

    2009-01-01

    The antimicrobial peptide ubiquicidin (UBI) directly labeled with technetium-99m ( 99m Tc) has recently been shown to be specifically taken up at sites of infection; however, its chemical structure is not well defined. To address this problem, the aim of the present study was to label UBI using poly(ethyleneglycol)-N-(N-(3-diphenylphosphinopropionyl)glycyl) -S-tritylcysteine ligand (PEG-PN 2 S) in order to compare its ability to detect infection sites with that of 99m Tc-UBI. Methods: The PN 2 S-PEG-UBI conjugate was prepared and labeled with 99m Tc, and its radiochemical purity was subsequently assessed. The stability of the conjugate to cysteine challenge and dilution with both saline solution and phosphate buffer was determined and serum stability and protein binding were also assessed. In vivo studies were carried out in healthy mice to study the biodistribution of 99m Tc-PN 2 S-PEG-UBI and its precursor 99m Tc-PN 2 S-PEG and in infected mice to compare the uptakes of 99m Tc-UBI and 99m Tc-PN 2 S-PEG-UBI at the site of infection using scintigraphic imaging and ex vivo tissue counting. Results: 99m Tc-PN 2 S-PEG-UBI was obtained with high radiochemical purity (98±1%) and high stability. The amphiphilic nature of the conjugate leads to a tendency to form micellar aggregates that explain the high protein binding values obtained. Biodistribution studies in mice showed low renal clearance followed by a predominant reticuloendothelial system clearance that limits its application in the abdominal area. Statistical analysis revealed no significant difference between 99m Tc-UBI and 99m Tc-PN 2 S-PEG-UBI uptake in infected mouse thigh, and the site of infection was clearly visualized using scintigraphic imaging. Conclusions: 99m Tc-PN 2 S-PEG-UBI proved to be as effective as 99m Tc-UBI in detecting sites of infection; however, the well-defined chemical structure of 99m Tc-PN 2 S-PEG-UBI makes it a better candidate for clinical imaging of infection

  17. Detection of sites of infection in mice using {sup 99m}Tc-labeled PN{sub 2}S-PEG conjugated to UBI and {sup 99m}Tc-UBI: a comparative biodistribution study

    Energy Technology Data Exchange (ETDEWEB)

    Melendez-Alafort, Laura [Department of Pharmaceutical Sciences, University of Padua, 35131 Padova (Italy)], E-mail: lmalafort@yahoo.com; Nadali, Anna; Pasut, Gianfranco; Zangoni, Elena [Department of Pharmaceutical Sciences, University of Padua, 35131 Padova (Italy); De Caro, Raffaele [Department of Anatomy and Physiology, University of Padua, 35131 Padova (Italy); Cariolato, Luca [Department of Pharmaceutical Sciences, University of Padua, 35131 Padova (Italy); Giron, Maria Cecilia [Department of Pharmacology and Anesthesiology, University of Padua, 35131 Padova (Italy); Castagliuolo, Ignazio [Department of Histology, Microbiology and Medical Biotechnologies, University of Padua, 35131 Padova (Italy); Veronese, Francesco M.; Mazzi, Ulderico [Department of Pharmaceutical Sciences, University of Padua, 35131 Padova (Italy)

    2009-01-15

    The antimicrobial peptide ubiquicidin (UBI) directly labeled with technetium-99m ({sup 99m}Tc) has recently been shown to be specifically taken up at sites of infection; however, its chemical structure is not well defined. To address this problem, the aim of the present study was to label UBI using poly(ethyleneglycol)-N-(N-(3-diphenylphosphinopropionyl)glycyl) -S-tritylcysteine ligand (PEG-PN{sub 2}S) in order to compare its ability to detect infection sites with that of {sup 99m}Tc-UBI. Methods: The PN{sub 2}S-PEG-UBI conjugate was prepared and labeled with {sup 99m}Tc, and its radiochemical purity was subsequently assessed. The stability of the conjugate to cysteine challenge and dilution with both saline solution and phosphate buffer was determined and serum stability and protein binding were also assessed. In vivo studies were carried out in healthy mice to study the biodistribution of {sup 99m}Tc-PN{sub 2}S-PEG-UBI and its precursor {sup 99m}Tc-PN{sub 2}S-PEG and in infected mice to compare the uptakes of {sup 99m}Tc-UBI and {sup 99m}Tc-PN{sub 2}S-PEG-UBI at the site of infection using scintigraphic imaging and ex vivo tissue counting. Results: {sup 99m}Tc-PN{sub 2}S-PEG-UBI was obtained with high radiochemical purity (98{+-}1%) and high stability. The amphiphilic nature of the conjugate leads to a tendency to form micellar aggregates that explain the high protein binding values obtained. Biodistribution studies in mice showed low renal clearance followed by a predominant reticuloendothelial system clearance that limits its application in the abdominal area. Statistical analysis revealed no significant difference between {sup 99m}Tc-UBI and {sup 99m}Tc-PN{sub 2}S-PEG-UBI uptake in infected mouse thigh, and the site of infection was clearly visualized using scintigraphic imaging. Conclusions: {sup 99m}Tc-PN{sub 2}S-PEG-UBI proved to be as effective as {sup 99m}Tc-UBI in detecting sites of infection; however, the well-defined chemical structure of {sup 99m

  18. Frontal cortex electrophysiology in reward- and punishment-related feedback processing during advice-guided decision making: An interleaved EEG-DC stimulation study.

    Science.gov (United States)

    Wischnewski, Miles; Bekkering, Harold; Schutter, Dennis J L G

    2018-04-01

    During decision making, individuals are prone to rely on external cues such as expert advice when the outcome is not known. However, the electrophysiological correlates associated with outcome uncertainty and the use of expert advice are not completely understood. The feedback-related negativity (FRN), P3a, and P3b are event-related brain potentials (ERPs) linked to dissociable stages of feedback and attentional processing during decision making. Even though these ERPs are influenced by both reward- and punishment-related feedback, it remains unclear how extrinsic information during uncertainty modulates these brain potentials. In this study, the effects of advice cues on decision making were investigated in two separate experiments. In the first experiment, electroencephalography (EEG) was recorded in healthy volunteers during a decision-making task in which the participants received reward or punishment feedback preceded by novice, amateur, or expert advice. The results showed that the P3a component was significantly influenced by the subjective predictive value of an advice cue, whereas the FRN and P3b were unaffected by the advice cues. In the second, sham-controlled experiment, cathodal transcranial direct current stimulation (ctDCS) was administered in conjunction with EEG in order to explore the direct contributions of the frontal cortex to these brain potentials. Results showed no significant change in either advice-following behavior or decision times. However, ctDCS did decrease FRN amplitudes as compared to sham, with no effect on the P3a or P3b. Together, these findings suggest that advice information may act primarily on attention allocation during feedback processing, whereas the electrophysiological correlates of the detection and updating of internal prediction models are not affected.

  19. Electrophysiologic studies in atrial fibrillation. Slow conduction of premature impulses: a possible manifestation of the background for reentry.

    Science.gov (United States)

    Cosio, F G; Palacios, J; Vidal, J M; Cocina, E G; Gómez-Sánchez, M A; Tamargo, L

    1983-01-01

    Extrastimulus-induced intraatrial conduction delays were measured in 12 patients with documented episodes of atrial fibrillation (AF) by recording atrial electrograms at the high right atrium, His bundle region, and coronary sinus. Seventeen patients with and without heart disease, but without atrial arrhythmias served as the control group. During baseline-paced atrial rhythms, a conduction delay zone could be delineated, near the atrial effective refractory period, during which all extrastimuli produced conduction delays. When compared at the same paced cycle lengths (500 to 650 ms), the patients with AF had shorter atrial effective refractory periods (mean +/- standard deviation 206 +/- 24.1 versus 233 +/- 28.2 in control patients, p less than 0.02), wider conduction delay zones (79 +/- 21.7 ms versus 52 +/- 21 in control patients, p less than 0.01), and longer conduction delays both to the His bundle region (64 +/- 18.3 ms versus 35 +/- 21.7 in control patients, p less than 0.005) and the coronary sinus (76 +/- 18.9 ms versus 35 +/- 16.1 in control patients, p less than 0.001). Repetitive atrial responses were recorded in 6 patients with AF and in 9 control subjects. Sinus nodal function abnormalities were detected in 6 of the patients with fibrillation. Patients with AF had a higher tendency than control subjects to develop slow intraatrial conduction, as well as shorter effective refractory periods. Since both features would favor reentry, they may be the electrophysiologic manifestations of the abnormalities making these patients prone to atrial reentrant arrhythmias. Repetitive atrial responses were of no predictive value. Sinus nodal dysfunction was frequently found, but was not essential for the occurrence of AF.

  20. Electrophysiology of Axonal Constrictions

    Science.gov (United States)

    Johnson, Christopher; Jung, Peter; Brown, Anthony

    2013-03-01

    Axons of myelinated neurons are constricted at the nodes of Ranvier, where they are directly exposed to the extracellular space and where the vast majority of the ion channels are located. These constrictions are generated by local regulation of the kinetics of neurofilaments the most important cytoskeletal elements of the axon. In this paper we discuss how this shape affects the electrophysiological function of the neuron. Specifically, although the nodes are short (about 1 μm) in comparison to the distance between nodes (hundreds of μm) they have a substantial influence on the conduction velocity of neurons. We show through computational modeling that nodal constrictions (all other features such as numbers of ion channels left constant) reduce the required fiber diameter for a given target conduction velocity by up to 50% in comparison to an unconstricted axon. We further show that the predicted optimal fiber morphologies closely match reported fiber morphologies. Supported by The National Science Foundation (IOS 1146789)

  1. Electrophysiologic Findings and Pain in Carpal Tunnel Syndrome

    Directory of Open Access Journals (Sweden)

    Hava Dönmez Keklikoğlu

    2009-12-01

    Full Text Available OBJECTIVE: Carpal tunnel syndrome (CTS is defined as median nerve entrapment within the carpal tunnel at the wrist. Pain and paresthesia are the most common presenting symptoms of the patients. In this study, our aim was to identify the association between intensity of presenting symptoms and electrophysiologic findings in patients referred to the electrophysiology laboratory with prediagnosis of CTS. METHODS: Sixty-two consecutive patients who were referred to the electrophysiology laboratory with the diagnosis of CTS were enrolled in the study. The intensity of pain was determined by visual analog scale, the findings of Tinel-Phalen tests were assessed, and clinico-demographic findings were recorded. Nerve conduction studies were performed bilaterally in median and ulnar nerves. The severity of CTS was determined with electrophysiologic evaluation, and the association between electrophysiologic findings and symptoms were analyzed statistically. RESULTS: Sixty-two (57 female, 5 male patients were examined in the study. CTS was bilateral in 53 patients and unilateral in 9 patients (total 115 hands. Mean pain score was 5.78 ± 3.50. In 28 hands with a clinical diagnosis of CTS, no electrophysiologic CTS findings were found, whereas in 32 hands mild, in 41 hands moderate and in 14 hands severe findings were obtained. CONCLUSION: According to our study, there was no statistically significant association between severity of symptoms and severity of electrophysiologic findings in CTS

  2. Quantitative cumulative biodistribution of antibodies in mice

    Science.gov (United States)

    Yip, Victor; Palma, Enzo; Tesar, Devin B; Mundo, Eduardo E; Bumbaca, Daniela; Torres, Elizabeth K; Reyes, Noe A; Shen, Ben Q; Fielder, Paul J; Prabhu, Saileta; Khawli, Leslie A; Boswell, C Andrew

    2014-01-01

    The neonatal Fc receptor (FcRn) plays an important and well-known role in antibody recycling in endothelial and hematopoietic cells and thus it influences the systemic pharmacokinetics (PK) of immunoglobulin G (IgG). However, considerably less is known about FcRn’s role in the metabolism of IgG within individual tissues after intravenous administration. To elucidate the organ distribution and gain insight into the metabolism of humanized IgG1 antibodies with different binding affinities FcRn, comparative biodistribution studies in normal CD-1 mice were conducted. Here, we generated variants of herpes simplex virus glycoprotein D-specific antibody (humanized anti-gD) with increased and decreased FcRn binding affinity by genetic engineering without affecting antigen specificity. These antibodies were expressed in Chinese hamster ovary cell lines, purified and paired radiolabeled with iodine-125 and indium-111. Equal amounts of I-125-labeled and In-111-labeled antibodies were mixed and intravenously administered into mice at 5 mg/kg. This approach allowed us to measure both the real-time IgG uptake (I-125) and cumulative uptake of IgG and catabolites (In-111) in individual tissues up to 1 week post-injection. The PK and distribution of the wild-type IgG and the variant with enhanced binding for FcRn were largely similar to each other, but vastly different for the rapidly cleared low-FcRn-binding variant. Uptake in individual tissues varied across time, FcRn binding affinity, and radiolabeling method. The liver and spleen emerged as the most concentrated sites of IgG catabolism in the absence of FcRn protection. These data provide an increased understanding of FcRn’s role in antibody PK and catabolism at the tissue level. PMID:24572100

  3. Biodistribution and PET imaging of [18F]-fluoroadenosine derivatives

    International Nuclear Information System (INIS)

    Alauddin, Mian M.; Shahinian, Antranik; Park, Ryan; Tohme, Michael; Fissekis, John D.; Conti, Peter S.

    2007-01-01

    Introduction: Many fluorinated analogues of adenosine nucleoside have been synthesized and studied as potential antitumor and antiviral agents. Earlier, we reported radiosynthesis of 2'-deoxy-2'-[ 18 F]fluoro-1-β-D-arabinofuranosyl-adenine ([ 18 F]-FAA) and 3'-deoxy-3'-[ 18 F]fluoro-1-β-D-xylofuranosyl-adenine ([ 18 F]FXA). Now, we report their in vivo studies including blood clearance, biodistribution and micro-PET imaging in tumor-bearing nude mice. Methods: Tumors were grown in 6-week-old athymic nude mice (Harlan, Indianapolis, IN, USA) by inoculation of HT-29 cells, wild-type cells in the left flank and transduced cells with HSV-tk on the right flank. When the tumor was about 1 cm in size, animals were injected with these radiotracers for in vivo studies, including blood clearance, micro-PET imaging and biodistribution. Results: Uptake of [ 18 F]FAA in tumor was 3.3-fold higher than blood, with highest uptake in the spleen. Maximum uptake of [ 18 F]FXA was observed in the heart compared to other organs. There was no tumor uptake of [ 18 F]FXA. Biodistribution results were supported by micro-PET images, which also showed very high uptake of [ 18 F]FAA in spleen and visualization of tumors, and high uptake of [ 18 F]FXA in the heart. Conclusion: These results suggest that [ 18 F]FAA may be useful for tumor imaging, while [ 18 F]FXA may have potential as a heart imaging agent with PET

  4. Pharmacokinetics and biodistribution of radiolabeled avidin, streptavidin and biotin

    International Nuclear Information System (INIS)

    Rosebrough, S.F.

    1993-01-01

    The extraordinarily high affinity of avidin and streptavidin for biotin may be exploited in a two-step approach for delivering radiolabeled biotin derivatives suitable for imaging and therapy to target-bound streptavidin or avidin conjugated monoclonal antibodies (MAbs). The in vivo pharmacokinetics and biodistribution of radiolabeled avidin, streptavidin (SA) and DTPA-biocytinamide (DTPA-biotin) were studied in the rabbit and dog. SA circulated in the blood similar to other 60 kDa proteins, avidin cleared immediately and DTPA-biotin exhibited plasma clearance by glomerular filtration. (author)

  5. Radioiodine labeling of resveratrol and its biodistribution in mice

    International Nuclear Information System (INIS)

    Chen Bo; Yu Huixin; Tan Cheng; Lin Xiufeng; Zhang Li; Cao Guoxian; Luo Shineng

    2008-01-01

    In order to investigate the preparation of radioiodinated resveratrol and its biodistribution in mice, resveratrol was labeled with 131 I using lactoperoxidase methods and purified by ethyl acetate. The radiolabeled compound was characterized by polyamide TLC, in which the substratum of V trichoromethane : V acetone : V ethanol : V Adam's ale =4 : 4 : 0.5 : 0.4 was used as the developing agent. Biodistribution studies were accomplished on KM mice. At different time after radiopharmaceutical i.v. administration (0.185 MBq 131 I- tetrahydropalmatine/mouse), the animals were sacrificed (n=5 animals for each time). Blood and the interested tissues were collected, washed, weighted and counted. The percent injected dose per gram (%ID·g -1 ) was calculated for each sample. The labeling yield of 131 I-resveratrol is 69.3% and its RCPs are 95.9%, 92.0%, 90.4%, and 90.1% after 1, 3, 7 and 15 d, respectively. Biodistribution in mice demonstrates that 131 I-resveratrol is distributed into broad organs and tissues. However, it reveals higher levels in liver, kidney and intestine than in other tissues. In liver and kidney, the %ID· g -1 are 16.35% and 13.05% at 5 min, respectively. 131 I-resveratrol is metabolized mainly through liver and kidney. Simultaneously, its high distribution is also found in intestine. The %ID·g -1 of 131 I-resveratrol is 11.70% at 10 min; the activity in thyroid increases with time. Therefore, the 131 I-resveratrol is worthy of further investigation to trace the compound in vivo and ex vivo. (authors)

  6. Radioiodine-Labeling of Chlorpyrifos and Its Biodistribution in Mice

    Directory of Open Access Journals (Sweden)

    DIAO Yao

    2015-11-01

    Full Text Available To investigate the preparation of radioiodinated Chlorpyrifos and its biodistribution in mice, Chlorpyrifos was labeled with 131I using the Iodogen method. Biodistribution studies were carried out in KM mice. At different times after radiopharmaceutical i.v. administration (185 kBq 131I-Chlorpyrifos/mouse, n=5, the animals were sacrificed. Blood samples and the tissues of interested were collected, weighted and counted. The percentage of injected does per gram (%ID/g was calculated for each sample. The labeling yield of 131I-Chlorpyrifos was 93.5%, The radiochemical purity (RCP was 96.9%. Biodistribution in mice demonstrated that 131I-Chlorpyrifos was extensive, and the uptakes mainly occur in lung, stomach, small-intestine, colon, musle, and submaxillay gland, as indicated by their amount of 37.12%ID/g, 6.18%ID/g, 8.12%ID/g, 8.15%ID/g, 7.04%ID/g, and 7.02%ID/g at 10 min, respectively. And it was metabolized in liver and kidney, as indicated by their uptake of 4.34%ID/g and 8.50%ID/g at 5 min, and 0.22%ID/g and 0.69%ID/g at 4 h, respectively. In addition, 131I-Chlorpyrifos was cleared out from blood quickly, and the uptake of 131I-Chlorpyrifos in blood was 37.27%ID/g at 5 min, and decreased to 1.35%ID/g at 4 h post injection. In conclusion, 131I-Chlorpyrifos was stable in vitro and it was absorbed in lung and digestive tract, and it was metabolized mainly in liver and kidney, worthy of further investigation to trace the compound in vivo and in vitro.

  7. Radiolabeling, biodistribution and tumor imaging of stealth liposomes containing methotrexate

    International Nuclear Information System (INIS)

    Subramanian, N; Arulsudar, N; Chuttani, K; Mishra, P; Sharma, R.K; Murthy, R.S.R

    2003-01-01

    To study the utility of sterically stabilized liposomes (stealth liposomes) in tumor scintigraphy by studying its biodistribution and accumulation in target tissue after radiolabeling with Technetium-99m (99mTC). Conventional and Stealth liposomes were prepared by lipid film hydration method using methotrexate as model anticancer drug. Radiolabeling of the liposomes was carried out by direct labeling using reduced 99mTc. Experimental conditions for maximum labeling yield were optimized. The stability studies were carried out to check binding strength of the radiolabeled complexes. The blood kinetic study was carried out in rabbits after giving the labeled complex by intravenous administration through ear vein. The biodistribution studies were carried out in the Ehrlich ascites tumor (EAT) bearing mice after intravenous administration through tail vein, showed prolonged circulation in blood and significant increase in the accumulation in tumor for the sterically stabilized liposomes compared to the conventional liposomes. The gamma scintigraphic image shows the distribution of the stealth liposomes in liver, spleen, kidney and tumor. The study gives precise idea about the use of stealth liposomes in tumor scintigraphy and organ distribution studies (Au)

  8. Electrophysiology in visually impaired children

    NARCIS (Netherlands)

    Genderen, Maria Michielde van

    2006-01-01

    Inherited retinal disorders and posterior visual pathway abnormalities are important causes of visual impairment in children. Visual electrophysiology often is indispensable in diagnosing these conditions. This thesis shows the wide range of use of pediatric electro-ophthalmology, and demonstrates

  9. Application of Linear Mixed-Effects Models in Human Neuroscience Research: A Comparison with Pearson Correlation in Two Auditory Electrophysiology Studies.

    Science.gov (United States)

    Koerner, Tess K; Zhang, Yang

    2017-02-27

    Neurophysiological studies are often designed to examine relationships between measures from different testing conditions, time points, or analysis techniques within the same group of participants. Appropriate statistical techniques that can take into account repeated measures and multivariate predictor variables are integral and essential to successful data analysis and interpretation. This work implements and compares conventional Pearson correlations and linear mixed-effects (LME) regression models using data from two recently published auditory electrophysiology studies. For the specific research questions in both studies, the Pearson correlation test is inappropriate for determining strengths between the behavioral responses for speech-in-noise recognition and the multiple neurophysiological measures as the neural responses across listening conditions were simply treated as independent measures. In contrast, the LME models allow a systematic approach to incorporate both fixed-effect and random-effect terms to deal with the categorical grouping factor of listening conditions, between-subject baseline differences in the multiple measures, and the correlational structure among the predictor variables. Together, the comparative data demonstrate the advantages as well as the necessity to apply mixed-effects models to properly account for the built-in relationships among the multiple predictor variables, which has important implications for proper statistical modeling and interpretation of human behavior in terms of neural correlates and biomarkers.

  10. Preparation and biodistribution of radiolabeled fullerene C60 nanocrystals

    International Nuclear Information System (INIS)

    Nikolic, Nadezda; Vranjes-Duric, Sanja; Jankovic, Drina; Dokic, Divna; Mirkovic, Marija; Bibic, Natasa; Trajkovic, Vladimir

    2009-01-01

    The present study describes for the first time a procedure for the radiolabeling of fullerene (C 60 ) nanocrystals (nanoC 60 ) with Na 125 I, as well as the biodistribution of radiolabeled nanoC 60 ( 125 I-nanoC 60 ). The solvent exchange method with tetrahydrofuran was used to make colloidal water suspensions of radiolabeled nanoC 60 particles. The radiolabeling procedure with the addition of Na 125 I to tetrahydrofuran during dissolution of C 60 gave a higher radiochemical yield of radiolabeled nanoC 60 particles in comparison to the second option, in which Na 125 I was added after C 60 was dissolved. Using photon correlation spectroscopy and transmission electron microscopy, 125 I-nanoC 60 particles were found to have a crystalline structure and a mean diameter of 200-250 nm. The 125 I-nanoC 60 had a particularly high affinity for human serum albumin, displaying 95% binding efficiency after 1 h. Biodistribution studies of 125 I-nanoC 60 in rats indicated significant differences in tissue accumulation of 125 I-nanoC 60 and the radioactive tracer Na 125 I. The higher accumulation of radiolabeled nanoC 60 was observed in liver and spleen, while accumulation in thyroid, stomach, lungs and intestines was significantly lower in comparison to Na 125 I. In addition to being useful for testing the biological distribution of nanoC 60 , the described radiolabeling procedure might have possible applications in cancer radiotherapy.

  11. The reliability of commonly used electrophysiology measures.

    Science.gov (United States)

    Brown, K E; Lohse, K R; Mayer, I M S; Strigaro, G; Desikan, M; Casula, E P; Meunier, S; Popa, T; Lamy, J-C; Odish, O; Leavitt, B R; Durr, A; Roos, R A C; Tabrizi, S J; Rothwell, J C; Boyd, L A; Orth, M

    Electrophysiological measures can help understand brain function both in healthy individuals and in the context of a disease. Given the amount of information that can be extracted from these measures and their frequent use, it is essential to know more about their inherent reliability. To understand the reliability of electrophysiology measures in healthy individuals. We hypothesized that measures of threshold and latency would be the most reliable and least susceptible to methodological differences between study sites. Somatosensory evoked potentials from 112 control participants; long-latency reflexes, transcranial magnetic stimulation with resting and active motor thresholds, motor evoked potential latencies, input/output curves, and short-latency sensory afferent inhibition and facilitation from 84 controls were collected at 3 visits over 24 months at 4 Track-On HD study sites. Reliability was assessed using intra-class correlation coefficients for absolute agreement, and the effects of reliability on statistical power are demonstrated for different sample sizes and study designs. Measures quantifying latencies, thresholds, and evoked responses at high stimulator intensities had the highest reliability, and required the smallest sample sizes to adequately power a study. Very few between-site differences were detected. Reliability and susceptibility to between-site differences should be evaluated for electrophysiological measures before including them in study designs. Levels of reliability vary substantially across electrophysiological measures, though there are few between-site differences. To address this, reliability should be used in conjunction with theoretical calculations to inform sample size and ensure studies are adequately powered to detect true change in measures of interest. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Effect of the spider toxin Tx3-3 on spinal processing of sensory information in naive and neuropathic rats: an in vivo electrophysiological study.

    Science.gov (United States)

    Dalmolin, Gerusa D; Bannister, Kirsty; Gonçalves, Leonor; Sikandar, Shafaq; Patel, Ryan; Cordeiro, Marta do Nascimento; Gomez, Marcus Vinícius; Ferreira, Juliano; Dickenson, Anthony H

    2017-07-01

    Drugs that counteract nociceptive transmission in the spinal dorsal horn preferentially after nerve injury are being pursued as possible neuropathic pain treatments. In a previous behavioural study, the peptide toxin Tx3-3, which blocks P/Q- and R-type voltage-gated calcium channels, was effective in neuropathic pain models. In the present study, we aimed to investigate the effect of Tx3-3 on dorsal horn neuronal responses in rats under physiological conditions and neuropathic pain condition induced by spinal nerve ligation (SNL). In vivo electrophysiological recordings of dorsal horn neuronal response to electrical and natural (mechanical and thermal) stimuli were made in rats under normal physiological state (naive rats) or after the SNL model of neuropathic pain. Tx3-3 (0.3-100 pmol/site) exhibited greater inhibitory effect on electrical-evoked neuronal response of SNL rats than naive rats, inhibiting nociceptive C-fibre and Aδ-fibre responses only in SNL rats. The wind-up of neurones, a measurement of spinal cord hyperexcitability, was also more susceptible to a dose-related inhibition by Tx3-3 after nerve injury. Moreover, Tx3-3 exhibited higher potency to inhibit mechanical- and thermal-evoked neuronal response in conditions of neuropathy. Tx3-3 mediated differential inhibitory effect under physiological and neuropathic conditions, exhibiting greater potency in conditions of neuropathic pain.

  13. Macroscopic and microscopic biodistribution of intravenously administered iron oxide nanoparticles

    Science.gov (United States)

    Misra, Adwiteeya; Petryk, Alicia A.; Strawbridge, Rendall R.; Hoopes, P. Jack

    2015-03-01

    Iron oxide nanoparticles (IONP) are being developed for use as a cancer treatment. They have demonstrated efficacy when used either as a monotherapy or in conjunction with conventional chemotherapy and radiation. The success of IONP as a therapeutic tool depends on the delivery of a safe and controlled cytotoxic thermal dose to tumor tissue following activation with an alternating magnetic field (AMF). Prior to clinical approval, knowledge of IONP toxicity, biodistribution and physiological clearance is essential. This preliminary time-course study determines the acute toxicity and biodistribution of 110 nm dextran-coated IONP (iron) in mice, 7 days post systemic, at doses of 0.4, 0.6, and 1.0 mg Fe/ g mouse bodyweight. Acute toxicity, manifested as changes in the behavior of mice, was only observed temporarily at 1.0 mg Fe/ g mouse bodyweight, the highest dose administered. Regardless of dose, mass spectrometry and histological analysis demonstrated over 3 mg Fe/g tissue in organs within the reticuloendotheilial system (i.e. liver, spleen, and lymph nodes). Other organs (brain, heart, lungs, and kidney) had less than 0.5 mg Fe/g tissue with iron predominantly confined to the organ vasculature.

  14. 99mTc-tetrapeptides: radiolabelling and biodistribution in rats

    International Nuclear Information System (INIS)

    Laznickova, A.; Laznicek, M.; Trejtnar, F.; Mather, S.J.

    1998-01-01

    Preparation of 99m Tc-labelled tetrapeptides, namely acetyl-Gly-Gly-Cys-Gly (I), acetyl-Ser-Ser-Cys-Gly (II) and acetyl-Gly-Gly-Cys-Lys (III), analysis of their radiochemical purity and biodistribution were investigated in rats. The aim was to determine the relationship between structure and biological behaviour of 99m Tc-labelled peptides which are formed by amino-acid sequences capable of chelating technetium useful as universal chelators in ''hybrid'' peptides composed of receptor-specific part and the part chelating technetium. For labelling with 99m Tc, a conventional transchelation from 99m Tc-gluconate was used and radiolabelled peptides were purified by filtration on Whatman microfilters 12 kD. Radiochemical purity was higher than 98%. Biodistribution studies in rats showed that all agents are rapidly cleared from the body mostly via urine, but some part of administered radioactivity also in the faces was found. The later route of elimination way increased in the order III 99m Tc-MAG3. The results obtained will assist with design of optimal biocompatible tetrapeptides as chelators for formation of hybrid receptor-specific peptides. (author)

  15. Drugs that alter biodistribution and kinetics of radiopharmaceuticals

    International Nuclear Information System (INIS)

    Shani, J.

    1986-01-01

    Target localization and organ biodistribution of radiopharmaceuticals (RPs) may be altered by non-radioactive drugs whose pharmacological mechanisms compete with the RPs for the same retention processes. Originally referred to as side effects or incompatibilities, such interactions became a major concern in evaluating Nuclear Medicine procedures, as they might cause interpretation of the latter to be without value or misleading. With accumulated experience, some interactions were intentionally included in Nuclear Medicine procedures and became an additional tool in differential diagnosis. Moreover, due to the ability of some RPs to compete with therapeutic agents, Nuclear Medicine studies shifted from anatomical-physiological to more pharmacologically-pathologically-based procedures that can also monitor the stage of disease, and follow its treatment. The aim of this review, therefore, is not only to illustrate some crucial pharmacological issues in Nuclear Medicine imaging, but to emphasize the possible input that alterations of RP biodistribution by drugs may have in achieving better and safer diagnosis, disease staging and monitoring of the patient's response to therapy. 166 references

  16. Biodistribution and human dosimetry estimation of fluoro-L-DOPA as PET imaging agent of dopaminergic nerve transmitter systems

    International Nuclear Information System (INIS)

    Tang Ganghua; Wang Mingfang; Luo Lei; Gan Manquan; Tang Xiaolan; Zhang Lan; Wang Yongxian

    2002-01-01

    Objective: To investigate the biodistribution and human dosimetry estimation of 6-[ 18 F] Fluoro-L-DOPA (FDOPA). Methods: Biodistribution of FDOPA in normal rats and brain of hemi-Parkinsonism rats were determined. Human dosimetry estimation was performed by MIRD method based on the rats biodistribution data. Results: Biodistributions in normal rats showed high uptake in kidney, blood, striatum and hippocampi, fast clearance of radioactivity from kidney and blood, longer retain time in striatum and hippocampi, and higher striatum to cerebellum and striatum to cortex ratio. FDOPA uptake, striatum to cerebellum and striatum to cortex ratio in the lesioned side of hemi-Parkinsonism rats (P 2 to 2.3 x 10 -2 mGy/MBq and the effective dose in humans was estimated to be 2.05 x 10 -2 mSv/MBq after injection of FDOPA based on rats biodistribution data, which were consistent with those reported by literature on the whole. Conclusion: Human radiation dosimetry of FDOPA and other PET tracers can be estimated based on animals biodistribution data. The synthetic FDOPA is safe and efficient and can be used in animals, human and PD patients PET studies

  17. Automatic Parameterization Strategy for Cardiac Electrophysiology Simulations

    OpenAIRE

    Costa, Caroline Mendonca; Hoetzl, Elena; Rocha, Bernardo Martins; Prassl, Anton J; Plank, Gernot

    2013-01-01

    Driven by recent advances in medical imaging, image segmentation and numerical techniques, computer models of ventricular electrophysiology account for increasingly finer levels of anatomical and biophysical detail. However, considering the large number of model parameters involved parameterization poses a major challenge. A minimum requirement in combined experimental and modeling studies is to achieve good agreement in activation and repolarization sequences between model and experiment or ...

  18. Effects of broccoli extract on biodistribution and labeling blood components with 99mTc-GH

    International Nuclear Information System (INIS)

    Cekic, Betul; Muftuler, Fazilet Zumrut Biber; Kilcar, Ayfer Yurt; Ichedef, Cigdem; Unak, Perihan

    2011-01-01

    Purpose: people consume vegetables without the knowledge of the side effects of the biological and chemical contents and interactions between radiopharmaceuticals and herbal extract. To this end, current study is focused on the effects of broccoli extract on biodistribution of radiolabeled glucoheptonate ( 99m Tc-GH) and radiolabeling of blood components. Methods: GH was labeled with 99m Tc. Quality control studies were done utilizing TLC method. Biodistribution studies were performed on male rats which were treated via gavage with either broccoli extract or SF as control group for 15 days. Blood samples were withdrawn from rats' heart. Radiolabeling of blood constituents performed incubating with GH, SnCl 2 and 99m Tc. Results: radiochemical yield of 99m Tc-GH is 98.46±1.48 % (n=8). Biodistribution studies have shown that according to the control, the treated group with broccoli has approximately 10 times less uptake in kidney. The percentage of the radioactivity ratios of the blood components is found to be same in both groups. Conclusions: although there is no considerable effect on the radiolabeling of blood components, there is an outstanding change on the biodistribution studies especially on kidneys. The knowledge of this change on kidney uptake may contribute to reduce the risk of misdiagnosis and/or repetition of the examinations in Nuclear Medicine. (author)

  19. Frontal cortex electrophysiology in reward- and punishment-related feedback processing during advice-guided decision making: An interleaved EEG-DC stimulation study

    NARCIS (Netherlands)

    Wischnewski, M.; Bekkering, H.; Schutter, D.J.L.G.

    2018-01-01

    During decision making, individuals are prone to rely on external cues such as expert advice when the outcome is not known. However, the electrophysiological correlates associated with outcome uncertainty and the use of expert advice are not completely understood. The feedback-related negativity

  20. Biodistribution of 212Pb Conjugated Trastuzumab in Mice

    International Nuclear Information System (INIS)

    Schneider, N.; Lobaugh, M.; Sandwall, P.; Glover, S.; Murry, M.; Dong, Z.; Spitz, H.

    2014-01-01

    Clinical use of radiolabeled monoclonal antibodies in therapeutic treatment of cancer is increasing. This study demonstrates an increased uptake rate in the tumor over a 72 hr period of observation following a single intravenous injection of 212Pb-trastuzumab in mice. Whereas 212Pb-trastuzumab appeared not to cause systemic toxicity4, there may be concomitant uptake in other organs that should be considered in evaluating the risk of radiation toxicity associated with therapy. Additional laboratory and clinical study with 212Pb-trastuzumab should be conducted to define an optimized therapeutic strategy and determine the radiation doses delivered to non-targeted organs and tissues using microdosimetry methods. Results of this biodistribution study support further investigation of radiolabeled 212Pb-TCMC-trastuzumab, radiobiological organ microdosimetry, and optimal dosing regimens for 212Pb-trastuzumab as a therapeutic agent

  1. Biodistribution, toxicity and radiation dosimetry studies of the serotonin transporter radioligand 4-[{sup 18}F]-ADAM in rats and monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Ya-Yao [Tri-Service General Hospital, PET Center, Department of Nuclear Medicine, Taipei (China); National Tsing Hua University, Department of Biomedical Engineering and Environmental Sciences, Hsinchu (China); Ma, Kuo-Hsing [National Defense Medical Center, Department of Biology and Anatomy, Taipei (China); Tseng, Ta-Wei; Chou, Ta-Kai; Huang, Wen-Sheng [Tri-Service General Hospital, PET Center, Department of Nuclear Medicine, Taipei (China); Ng, Hanna; Mirsalis, Jon C. [SRI International, Menlo Park, CA (United States); Fu, Ying-Kai [Institute of Nuclear Energy Research, Taoyuan (China); Chung Yuan Christian University, Department of Chemistry, Chung-Li (China); Chu, Tieh-Chi [National Tsing Hua University, Department of Biomedical Engineering and Environmental Sciences, Hsinchu (China); Yuanpei University, Department of Radiological Technology, Hsinchu (China); Shiue, Chyng-Yann [Tri-Service General Hospital, PET Center, Department of Nuclear Medicine, Taipei (China); University of Pennsylvania, Department of Radiology, Philadelphia, PA (United States)

    2010-03-15

    4-[{sup 18}F]-ADAM is a potent serotonin transport imaging agent. We studied its toxicity in rats and radiation dosimetry in monkeys before human studies are undertaken. Single and multiple-dosage toxicity studies were conducted in Sprague-Dawley rats. Male and female rats were injected intravenously with 4-F-ADAM as a single dose of 1,023.7 {mu}g/kg (1,000 times the human dose) or as five consecutive daily doses of 102.37 {mu}g/kg (100 times the human dose). PET/CT scans were performed in seven Formosa Rock monkeys (four males and three females) using a Siemens Biograph scanner. After injection of 4-[{sup 18}F]-ADAM (182{+-}8 MBq), a low dose CT scan and a series of eight whole-body PET scans were performed. Whole-body images were acquired in 3-D mode. Time-activity data of source organs were used to calculate the residence times and estimate the absorbed radiation dose using OLINDA/EXM software. In the rats neither the single dose nor the five daily doses of 4-F-ADAM produced overt adverse effects clinically. In the monkeys the radiation doses received by most organs ranged between 7.1 and 35.7 {mu}Gy/MBq, and the urinary bladder was considered to be the critical organ. The effective doses extrapolated to male and female adult humans were 17.4 and 21.8 {mu}Sv/MBq, respectively. Toxicity studies in Sprague-Dawley rats and radiation dosimetry studies in Formosa Rock monkeys suggested that 4-[{sup 18}F]-ADAM is safe for use in human PET imaging studies. (orig.)

  2. Effects of concurrent drug therapy on technetium /sup 99m/Tc gluceptate biodistribution

    International Nuclear Information System (INIS)

    Hinkle, G.H.; Basmadjian, G.P.; Peek, C.; Barker, K.K.; Ice, R.D.

    1982-01-01

    Drug interactions with /sup 99m/Tc gluceptate resulting in altered biodistribution were studied using chart review and animal tests. Charts of nine patients who had abnormal gallbladder uptake of technetium /sup 99m/Tc gluceptate during a two-year period were reviewed to obtain data such as concurrent drug therapy, primary diagnosis, and laboratory values. Adult New Zealand white rabbits were then used for testing the biodistribution of technetium /sup 99m/Tc gluceptate when administered concurrently with possibly interacting drugs identified in the chart review--penicillamine, penicillin G potassium, penicillin V potassium, acetaminophen, and trimethoprim-sulfamethoxazole. Chart review revealed no conclusive patterns of altered biodistribution associated with other factors. The data did suggest the possibility that the five drugs listed above might cause increased hepatobiliary clearance of the radiopharmaceutical. Animal tests showed that i.v. penicillamine caused substantial distribution of radioactivity into the gallbladder and small bowel. Minimally increased gallbladder radioactivity occurred when oral acetaminophen and trimethoprim-sulfamethoxazole were administered concurrently. Oral and i.v. penicillins did not increase gallbladder activity. Penicillamine may cause substantial alteration of the biodistribution of technetium /sup 99m/Tc gluceptate

  3. Biodistribution and pharmacokinetic of 1E10 monoclonal antibody after subcutaneous administration in healthy mice

    International Nuclear Information System (INIS)

    León, M; Hernández, I; Aldana, L; Ayra, F; Castro, Y; Leyva, R; García, L; Casaco, A

    2016-01-01

    To evaluate biodistribution and pharmacokinetic of the 1E10, the molecule was radio labelled with 125I and incorporated into a cold antibody formulation. Isotopic labeling was carried out by means of standardized methods.Introduction:1E10 monoclonal antibody was developed at Centre of Molecular Immunology (CIM) as antitumoral drug with proved efficacy in experimental models. In the present investigation, biodistribution and pharmacokinetic studies were conducted with the help of radio isotopic labeling. Materials and methods: 1E10 was supplied by CIM and labeled with 125I by the iodogen method. To male Balb/c mice from CENPALAB a single subcutaneous administration of 1 mg/kg was performed in the supra scapular region and accommodated in metabolic cages during experiments. Blood samples were taken alternating five groups of three animals according with a sparse data design. Biodistribution was carried out by direct organ sampling and radioactive counting. Pharmacokinetic was performed by compartmental analysis. Urine and faces were collected at regular time intervals. Results: Observed pharmacokinetic behaviour is typical of an immunoglobulin in the assay system used, showing a slow clearance and a small volume of distribution. Biodistribution shows no preference for any sampled organs or tissues. Only a high relative uptake was observed in axillary and brachial lymph nodes close to administration site. (author)

  4. Biodistribution and radiation dosimetry of the 18 kDa translocator protein (TSPO) radioligand [{sup 18}F]FEDAA1106: a human whole-body PET study

    Energy Technology Data Exchange (ETDEWEB)

    Takano, Akihiro; Gulyas, Balazs; Varrone, Andrea; Karlsson, Per; Sjoholm, Nils; Halldin, Christer [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm (Sweden); Larsson, Stig; Jonsson, Cathrine; Odh, Richard [Karolinska Institutet, Department of Nuclear Medicine, Stockholm (Sweden); Sparks, Richard [CDE Dosimetry Services, Inc., Knoxville, TN (United States); Tawil, Nabil Al [Karolinska University Hospital, Karolinska Trial Alliance, Stockholm (Sweden); Hoffmann, Anja; Zimmermann, Torsten; Thiele, Andrea [Bayer Schering Pharma AG, Berlin (Germany)

    2011-11-15

    [{sup 18}F]FEDAA1106 is a recently developed positron emission tomography (PET) radioligand for in vivo quantification of the 18 kDa translocator protein [TSPO or, as earlier called, the peripheral benzodiazepine receptor (PBR)]. TSPO imaging is expected to be useful for the clinical evaluation of neuroinflammatory diseases. The aim of this study was to provide dosimetry estimates for [{sup 18}F]FEDAA1106 based on human whole-body PET measurements. PET scans were performed for a total of 6.6 h after the injection of 183.8 {+-} 9.1 MBq of [{sup 18}F]FEDAA1106 in six healthy subjects. Regions of interest were drawn on coronal images. Estimates of the absorbed doses of radiation were calculated using the OLINDA software. Peak uptake was largest in lungs, followed by liver, small intestine, kidney, spleen and other organs. Peak values of the percent injected dose (%ID) at a time after radioligand injection were calculated for the lungs (27.1%ID at 0.2 h), liver (21.1%ID at 0.6 h), small intestine (10.4%ID at 6.3 h), kidney (4.9%ID at 1.8 h) and spleen (4.6%ID at 0.6 h). The largest absorbed dose was found in the spleen (0.12 mSv/MBq), followed by kidneys (0.094 mSv/MBq). The calculated mean effective dose was 0.036 mSv/MBq. Based on the distribution and dose estimates, the estimated radiation burden of [{sup 18}F]FEDAA1106 is moderately higher than that of [{sup 18}F]fluorodeoxyglucose (FDG). In clinical studies, the administered activity of this radioligand ought to be adjusted in line with regional regulations. This result would be helpful for further clinical TSPO imaging studies. (orig.)

  5. [Automated processing of electrophysiologic signals].

    Science.gov (United States)

    Korenevskiĭ, N A; Gubanov, V V

    1995-01-01

    The paper outlines a diagram of a multichannel analyzer of electrophysiological signals while are significantly non-stationary (such as those of electroencephalograms, myograms, etc.), by using a method based on the ranging procedure by the change-over points which may be the points of infection, impaired locality, minima, maxima, discontinuity, etc.

  6. Hepatobiliary delivery of polyaminopolycarboxylate chelates: Synthesis and characterization of a cholic acid conjugate of EDTA and biodistribution and imaging studies with its indium-111 chelate

    Energy Technology Data Exchange (ETDEWEB)

    Betebenner, D.A.; Carney, P.L.; Zimmer, A.M.; Kazikiewicz, J.M.; Bruecher, E.S.; Sherry, A.D.; Johnson, D.K. (Abbott Laboratories, Abbott Park, Illinois (USA))

    1991-03-01

    A conjugate in which the steroid nucleus of cholic acid was linked to EDTA via an 11-atom spacer was obtained by reacting the succinimidyl ester of cholic acid with the amine formed by reaction of a benzyl isothiocyanate derivative of EDTA with N-(tert-butoxycarbonyl)ethylenediamine and subsequent deprotection. Potentiometric titration studies with model complexes showed that the EDTA moiety retained the ability to form 1:1 chelates of high thermodynamic stability, although formation constants were some 3-4 log K units lower for complexes of the conjugate than for the analogous chelates with underivatized EDTA. A complex formed between the cholic acid-EDTA conjugate and 111InIII was clearly rapidly into the liver when injected iv into mice, with subsequent excretion from the liver into the gastrointestinal tract being complete within 1 h of injection. Radioscintigraphic imaging studies conducted in a rabbit given the 111In-labeled conjugate also showed early liver uptake followed by rapid clearance from the liver into the intestine, with good visualization of the gallbladder in images obtained at 20-25 min postinjection. It is concluded that conjugation to cholic acid provides a useful means for the hepatobiliary delivery of EDTA chelates that otherwise exhibit predominantly extracellular distribution and renal clearance.

  7. Hepatobiliary delivery of polyaminopolycarboxylate chelates: Synthesis and characterization of a cholic acid conjugate of EDTA and biodistribution and imaging studies with its indium-111 chelate

    International Nuclear Information System (INIS)

    Betebenner, D.A.; Carney, P.L.; Zimmer, A.M.; Kazikiewicz, J.M.; Bruecher, E.S.; Sherry, A.D.; Johnson, D.K.

    1991-01-01

    A conjugate in which the steroid nucleus of cholic acid was linked to EDTA via an 11-atom spacer was obtained by reacting the succinimidyl ester of cholic acid with the amine formed by reaction of a benzyl isothiocyanate derivative of EDTA with N-(tert-butoxycarbonyl)ethylenediamine and subsequent deprotection. Potentiometric titration studies with model complexes showed that the EDTA moiety retained the ability to form 1:1 chelates of high thermodynamic stability, although formation constants were some 3-4 log K units lower for complexes of the conjugate than for the analogous chelates with underivatized EDTA. A complex formed between the cholic acid-EDTA conjugate and 111InIII was clearly rapidly into the liver when injected iv into mice, with subsequent excretion from the liver into the gastrointestinal tract being complete within 1 h of injection. Radioscintigraphic imaging studies conducted in a rabbit given the 111In-labeled conjugate also showed early liver uptake followed by rapid clearance from the liver into the intestine, with good visualization of the gallbladder in images obtained at 20-25 min postinjection. It is concluded that conjugation to cholic acid provides a useful means for the hepatobiliary delivery of EDTA chelates that otherwise exhibit predominantly extracellular distribution and renal clearance

  8. Personal semantics: Is it distinct from episodic and semantic memory? An electrophysiological study of memory for autobiographical facts and repeated events in honor of Shlomo Bentin.

    Science.gov (United States)

    Renoult, Louis; Tanguay, Annick; Beaudry, Myriam; Tavakoli, Paniz; Rabipour, Sheida; Campbell, Kenneth; Moscovitch, Morris; Levine, Brian; Davidson, Patrick S R

    2016-03-01

    Declarative memory is thought to consist of two independent systems: episodic and semantic. Episodic memory represents personal and contextually unique events, while semantic memory represents culturally-shared, acontextual factual knowledge. Personal semantics refers to aspects of declarative memory that appear to fall somewhere in between the extremes of episodic and semantic. Examples include autobiographical knowledge and memories of repeated personal events. These two aspects of personal semantics have been studied little and rarely compared to both semantic and episodic memory. We recorded the event-related potentials (ERPs) of 27 healthy participants while they verified the veracity of sentences probing four types of questions: general (i.e., semantic) facts, autobiographical facts, repeated events, and unique (i.e., episodic) events. Behavioral results showed equivalent reaction times in all 4 conditions. True sentences were verified faster than false sentences, except for unique events for which no significant difference was observed. Electrophysiological results showed that the N400 (which is classically associated with retrieval from semantic memory) was maximal for general facts and the LPC (which is classically associated with retrieval from episodic memory) was maximal for unique events. For both ERP components, the two personal semantic conditions (i.e., autobiographical facts and repeated events) systematically differed from semantic memory. In addition, N400 amplitudes also differentiated autobiographical facts from unique events. Autobiographical facts and repeated events did not differ significantly from each other but their corresponding scalp distributions differed from those associated with general facts. Our results suggest that the neural correlates of personal semantics can be distinguished from those of semantic and episodic memory, and may provide clues as to how unique events are transformed to semantic memory. Copyright © 2015 Elsevier

  9. Marine Natural Products Acting on the Acetylcholine-Binding Protein and Nicotinic Receptors: From Computer Modeling to Binding Studies and Electrophysiology

    Directory of Open Access Journals (Sweden)

    Denis Kudryavtsev

    2014-03-01

    Full Text Available For a small library of natural products from marine sponges and ascidians, in silico docking to the Lymnaea stagnalis acetylcholine-binding protein (AChBP, a model for the ligand-binding domains of nicotinic acetylcholine receptors (nAChRs, was carried out and the possibility of complex formation was revealed. It was further experimentally confirmed via competition with radioiodinated α-bungarotoxin ([125I]-αBgt for binding to AChBP of the majority of analyzed compounds. Alkaloids pibocin, varacin and makaluvamines С and G had relatively high affinities (Ki 0.5–1.3 μM. With the muscle-type nAChR from Torpedo californica ray and human neuronal α7 nAChR, heterologously expressed in the GH4C1 cell line, no competition with [125I]-αBgt was detected in four compounds, while the rest showed an inhibition. Makaluvamines (Ki ~ 1.5 μM were the most active compounds, but only makaluvamine G and crambescidine 359 revealed a weak selectivity towards muscle-type nAChR. Rhizochalin, aglycone of rhizochalin, pibocin, makaluvamine G, monanchocidin, crambescidine 359 and aaptamine showed inhibitory activities in electrophysiology experiments on the mouse muscle and human α7 nAChRs, expressed in Xenopus laevis oocytes. Thus, our results confirm the utility of the modeling studies on AChBPs in a search for natural compounds with cholinergic activity and demonstrate the presence of the latter in the analyzed marine biological sources.

  10. Dynamics of feeding responses in Pieris brassicae Linn. as a function of chemosensory input : a behavioural, ultrastructural and electrophysiological study

    NARCIS (Netherlands)

    Ma, W.C.

    1972-01-01

    The present study of contact chemoreception in Pieris brassicae L. is divided into three major parts, viz. 1. behavioural analyses, 2. the identification and description of sense organs and 3. investigations concerning the sensory physiology. In a separate section some

  11. Enhanced delivery of iodine for synchrotron stereotactic radiotherapy by means of intracarotid injection and blood-brain barrier disruption: Quantitative iodine biodistribution studies and associated dosimetry

    International Nuclear Information System (INIS)

    Adam, Jean-Francois; Biston, Marie-Claude; Joubert, Aurelie; Charvet, Anne-Marie; Le Bas, Jean-Francois; Esteve, Francois; Elleaume, Helene

    2005-01-01

    Purpose: Synchrotron stereotactic radiotherapy (SSR) is a binary cancer treatment modality that involves the selective accumulation of a high Z element, such as iodine, in tumors, followed by stereotactic irradiation with kilovoltage X-rays from a synchrotron source. The success of SSR is directly related to the absolute amount of iodine achievable in the tumor. The purposes of this preclinical study were to determine whether the delivery of iodine to brain tumor models in rats could be enhanced by the means of its intracarotid injection with or without a hyperosmotic solution and to evaluate corresponding absorbed X-ray doses. Methods and materials: Experiments were performed on four groups of F98 glioma-bearing rats, which received either intracarotid (IC) or intravenous (IV) infusions of a mixture (6 mL in 12 min) of an iodinated contrast agent associated or not with a transient blood-brain barrier opener (mannitol). The mixture volumetric proportions were 8/13 of Iomeron (C = 350 mg/mL) for 5/13 of mannitol or saline, respectively. Absolute iodine concentration kinetic was measured in vivo in the tumor, blood, contralateral and ipsilateral brain, and muscle by monochromatic computed tomography. Associated dosimetry was performed by computing the iodine dose enhancement factor (DEF) in each region and building dose distribution maps by analytical simulations. Results: Infusion of mannitol significantly enhanced iodine tumor uptake compared with the control values (p < 0.0001 and p = 0.0138, for IC and IV protocols, respectively). The mean iodine concentrations (C) reached 20.5 ± 0.98 mg/mL (DEF = 4.1) after administration of iodine and mannitol vs. 4.1 ± 1.2 mg/mL i.c. with serum (DEF = 1.6). The tumor iodine uptakes after jugular injection with mannitol (C = 4.4 ± 2.1 mg/mL, DEF = 1.7) were not significantly different from IC injection of iodine without mannitol (p = 0.8142). The IV injection of iodine with saline led to an iodine concentration in the tumor

  12. Electrophysiological Correlates of Subliminal Perception of Facial Expressions in Individuals with Autistic Traits: A Backward Masking Study

    OpenAIRE

    Vukusic, Svjetlana; Ciorciari, Joseph; Crewther, David P.

    2017-01-01

    People with Autism spectrum disorder (ASD) show difficulty in social communication, especially in the rapid assessment of emotion in faces. This study examined the processing of emotional faces in typically developing adults with high and low levels of autistic traits (measured using the Autism Spectrum Quotient—AQ). Event-related potentials (ERPs) were recorded during viewing of backward-masked neutral, fearful and happy faces presented under two conditions: subliminal (16 ms, below the leve...

  13. The influence of the diffusion of responsibility effect on outcome evaluations: electrophysiological evidence from an ERP study.

    Science.gov (United States)

    Li, Peng; Jia, Shiwei; Feng, Tingyong; Liu, Qiang; Suo, Tao; Li, Hong

    2010-10-01

    Previous studies have revealed that personal responsibility has an influence on outcome evaluation, although the way this influence works is still unclear. This study imitated the phenomenon of responsibility diffusion in a laboratory to examine the influence of the effect of responsibility diffusion on the processing of outcome evaluation using the event-related potential (ERP) technique. Participants of the study were required to perform the gambling task individually in the high-responsibility condition and with others in the low-responsibility scenario. Self-rating results showed that the participants felt more responsible for monetary loss and believed that they had more contributions to the monetary gains in the high-responsibility condition than in the low-responsibility situation. Both the feedback-related negativity (FRN) and the P300 were sensitive to the responsibility level, as evidenced by the enhanced amplitudes in the high-responsibility condition for both components. Further correlation analysis showed a negative correlation between FRN amplitudes and subjective rating scores (i.e., the higher the responsibility level, the larger the FRN amplitude). The results probably indicate that the FRN and P300 reflect personal responsibility processing under the social context of diffusion of responsibility. Copyright 2010 Elsevier Inc. All rights reserved.

  14. A phase 1 study of 131I-CLR1404 in patients with relapsed or refractory advanced solid tumors: dosimetry, biodistribution, pharmacokinetics, and safety.

    Directory of Open Access Journals (Sweden)

    Joseph J Grudzinski

    Full Text Available (131I-CLR1404 is a small molecule that combines a tumor-targeting moiety with a therapeutic radioisotope. The primary aim of this phase 1 study was to determine the administered radioactivity expected to deliver 400 mSv to the bone marrow. The secondary aims were to determine the pharmacokinetic (PK and safety profiles of (131I-CLR1404.Eight subjects with refractory or relapsed advanced solid tumors were treated with a single injection of 370 MBq of (131I-CLR1404. Whole body planar nuclear medicine scans were performed at 15-35 minutes, 4-6, 18-24, 48, 72, 144 hours, and 14 days post injection. Optional single photon emission computed tomography imaging was performed on two patients 6 days post injection. Clinical laboratory parameters were evaluated in blood and urine. Plasma PK was evaluated on (127I-CLR1404 mass measurements. To evaluate renal clearance of (131I-CLR1404, urine was collected for 14 days post injection. Absorbed dose estimates for target organs were determined using the RADAR method with OLINDA/EXM software.Single administrations of 370 MBq of (131I-CLR1404 were well tolerated by all subjects. No severe adverse events were reported and no adverse event was dose-limiting. Plasma (127I-CLR1404 concentrations declined in a bi-exponential manner with a mean t½ value of 822 hours. Mean Cmax and AUC(0-t values were 72.2 ng/mL and 15753 ng • hr/mL, respectively. An administered activity of approximately 740 MBq is predicted to deliver 400 mSv to marrow.Preliminary data suggest that (131I-CLR1404 is well tolerated and may have unique potential as an anti-cancer agent.ClinicalTrials.gov NCT00925275.

  15. Biodistribution and Pharmacokinetics Study of siRNA-loaded Anti-NTSR1-mAb-functionalized Novel Hybrid Nanoparticles in a Metastatic Orthotopic Murine Lung Cancer Model

    Directory of Open Access Journals (Sweden)

    Maryna Perepelyuk

    2016-01-01

    Full Text Available Small interfering RNA (siRNA is effective in silencing critical molecular pathways in cancer. The use of this tool as a treatment modality is limited by lack of an intelligent carrier system to enhance the preferential delivery of this molecule to specific targets in vivo. In the present study, the in vivo behavior of novel anti-NTSR1-mAb-functionalized antimutant K-ras siRNA-loaded hybrid nanoparticles, delivered by i.p. injection to non-small-cell lung cancer in mice models, was investigated and compared to that of a naked siRNA formulation. The siRNA in anti-NTSR1-mAb-functionalized hybrid nanoparticles was preferentially accumulated in tumor-bearing lungs and metastasized tumor for at least 48 hours while the naked siRNA formulation showed lack of preferential accumulation in all of the organs monitored. The plasma terminal half-life of nanoparticle-delivered siRNA was 11 times higher (17–1.5 hours than that of the naked siRNA formulation. The mean residence time and AUClast were 3.4 and 33 times higher than the corresponding naked siRNA formulation, respectively. High-performance liquid chromatography analysis showed that the hybrid nanoparticle carrier system protected the encapsulated siRNA against degradation in vivo. Our novel anti-NTSR1-mAb-functionalized hybrid nanoparticles provide a useful platform for in vivo targeting of siRNA for both experimental and clinical purposes.

  16. Diagnostic value of combined magnetic resonance imaging examination of brachial plexus and electrophysiological studies in multifocal motor neuropathy

    Directory of Open Access Journals (Sweden)

    Basta Ivana

    2014-01-01

    Full Text Available Background/Aim. Multifocal motor neuropathy (MMN is an immune-mediated disorder characterized by slowly progressive asymetrical weakness of limbs without sensory loss. The objective of this study was to investigate the involvement of brachial plexus using combined cervical magnetic stimulation and magnetic resonance imaging (MRI of plexus brachialis in patients with MMN. We payed special attention to the nerve roots forming nerves inervating weak muscles, but without detectable conduction block (CB using conventional nerve conduction studies. Methods. Nine patients with proven MMN were included in the study. In all of them MRI of the cervical spine and brachial plexus was performed using a Siemens Avanto 1.5 T unit, applying T1 and turbo spinecho T1 sequence, axial turbo spin-echo T2 sequence and a coronal fat-saturated turbo spin-echo T2 sequence. Results. In all the patients severe asymmetric distal weakness of muscles inervated by radial, ulnar, median and peroneal nerves was observed and the most striking presentation was bilateral wrist and finger drop. Three of them had additional proximal weakness of muscles inervated by axillar and femoral nerves. The majority of the patients had slightly increased cerebrospinal fluid (CSF protein content. Six of the patients had positive serum polyclonal IgM anti-GM1 antibodies. Electromyoneurography (EMG showed neurogenic changes, the most severe in distal muscles inervated by radial nerves. All the patients had persistent partial CBs outside the usual sites of nerve compression in radial, ulnar, median and peroneal nerves. In three of the patients cervical magnetic stimulation suggested proximal CBs between cervical root emergence and Erb’s point (prolonged motor root conduction time. In all the patients T2-weighted MRI revealed increased signal intensity in at least one cervical root, truncus or fasciculus of brachial plexus. Conclusion. We found clinical correlation between muscle weakness

  17. The comprehensive electrophysiological study of curcuminoids on delayed-rectifier K+ currents in insulin-secreting cells.

    Science.gov (United States)

    Kuo, Ping-Chung; Yang, Chia-Jung; Lee, Yu-Chi; Chen, Pei-Chun; Liu, Yen-Chin; Wu, Sheng-Nan

    2018-01-15

    Curcumin (CUR) has been demonstrated to induce insulin release from pancreatic β-cells; however, how curcuminoids (including demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC)) exert any possible effects on membrane ion currents inherently in insulin-secreting cells remains largely unclear. The effects of CUR and other structurally similar curcuminoids on ion currents in rat insulin-secreting (INS-1) insulinoma cells were therefore investigated in this study. The effects of these compounds on ionic currents and membrane potential were studied by patch-clamp technique. CUR suppressed the amplitude of delayed-rectifier K + current (I K(DR) ) in a time-, state- and concentration-dependent manner in these cells and the inhibition was not reversed by diazoxide, nicorandil or chlorotoxin. The value of dissociation constant for CUR-induced suppression of I K(DR) in INS-1 cells was 1.26μM. Despite the inability of CUR to alter the activation rate of I K(DR) , it accelerated current inactivation elicited by membrane depolarization. Increasing CUR concentrations shifted the inactivation curve of I K(DR) to hyperpolarized potential and slowed the recovery of I K(DR) inactivation. CUR, DMC, and BDMC all exerted depressant actions on I K(DR) amplitude to a similar magnitude, although DMC and BDMC did not increase current inactivation clearly. CUR slightly suppressed the peak amplitude of voltage-gated Na + current. CUR, DMC and BDMC depolarized the resting potential and increased firing frequency of action potentials. The CUR-mediated decrease of I K(DR) and the increase of current inactivation also occurred in βTC-6 INS-1 cells. Taken these results together, these effects may be one of the possible mechanisms contributing their insulin-releasing effect. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. The Impact of Subthalamic Deep Brain Stimulation on Sleep-Wake Behavior: A Prospective Electrophysiological Study in 50 Parkinson Patients.

    Science.gov (United States)

    Baumann-Vogel, Heide; Imbach, Lukas L; Sürücü, Oguzkan; Stieglitz, Lennart; Waldvogel, Daniel; Baumann, Christian R; Werth, Esther

    2017-05-01

    This prospective observational study was designed to systematically examine the effect of subthalamic deep brain stimulation (DBS) on subjective and objective sleep-wake parameters in Parkinson patients. In 50 consecutive Parkinson patients undergoing subthalamic DBS, we assessed motor symptoms, medication, the position of DBS electrodes within the subthalamic nucleus (STN), subjective sleep-wake parameters, 2-week actigraphy, video-polysomnography studies, and sleep electroencepahalogram frequency and dynamics analyses before and 6 months after surgery. Subthalamic DBS improved not only motor symptoms and reduced daily intake of dopaminergic agents but also enhanced subjective sleep quality and reduced sleepiness (Epworth Sleepiness Scale: -2.1 ± 3.8, p sleep efficiency (+5.2 ± 17.6%, p = .005) and deep sleep (+11.2 ± 32.2 min, p = .017) and increased accumulation of slow-wave activity over the night (+41.0 ± 80.0%, p = .005). Rapid eye movement sleep features were refractory to subthalamic DBS, and the dynamics of sleep as assessed by state space analyses did not normalize. Increased sleep efficiency was associated with active electrode contact localization more distant from the ventral margin of the left subthalamic nucleus. Subthalamic DBS deepens and consolidates nocturnal sleep and improves daytime wakefulness in Parkinson patients, but several outcomes suggest that it does not normalize sleep. It remains elusive whether modulated activity in the STN directly contributes to changes in sleep-wake behavior, but dorsal positioning of electrodes within the STN is linked to improved sleep-wake outcomes. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  19. Electrophysiologic Study of a Method of Euthanasia Using Intrathecal Lidocaine Hydrochloride Administered during Intravenous Anesthesia in Horses.

    Science.gov (United States)

    Aleman, M; Davis, E; Williams, D C; Madigan, J E; Smith, F; Guedes, A

    2015-01-01

    An intravenous (IV) overdose of pentobarbital sodium is the most commonly used method of euthanasia in veterinary medicine. However, this compound is not available in many countries or rural areas resulting in usage of alternative methods such as intrathecal lidocaine administration after IV anesthesia. Its safety and efficacy as a method of euthanasia have not been investigated in the horse. To investigate changes in mean arterial blood pressure and electrical activity of the cerebral cortex, brainstem, and heart during intrathecal administration of lidocaine. Our hypothesis was that intrathecal lidocaine affects the cerebral cortex and brainstem before affecting cardiovascular function. Eleven horses requiring euthanasia for medical reasons. Prospective observational study. Horses were anesthetized with xylazine, midazolam, and ketamine; and instrumented for recording of electroencephalogram (EEG), electrooculogram (EOG), brainstem auditory evoked response (BAER), and electrocardiogram (ECG). Physical and neurological (brainstem reflexes) variables were monitored. Mean arterial blood pressure was recorded throughout the study. Loss of cerebro-cortical electrical activity occurred up to 226 seconds after the end of the infusion of lidocaine solution. Cessation of brainstem function as evidenced by a lack of brainstem reflexes and disappearance of BAER occurred subsequently. Undetectable heart sounds, nonpalpable arterial pulse, and extremely low mean arterial blood pressure supported cardiac death; a recordable ECG was the last variable to disappear after the infusion (300-1,279 seconds). Intrathecal administration of lidocaine is an effective alternative method of euthanasia in anesthetized horses, during which brain death occurs before cardiac death. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

  20. Electrophysiological Correlates of Subliminal Perception of Facial Expressions in Individuals with Autistic Traits: A Backward Masking Study

    Directory of Open Access Journals (Sweden)

    Svjetlana Vukusic

    2017-05-01

    Full Text Available People with Autism spectrum disorder (ASD show difficulty in social communication, especially in the rapid assessment of emotion in faces. This study examined the processing of emotional faces in typically developing adults with high and low levels of autistic traits (measured using the Autism Spectrum Quotient—AQ. Event-related potentials (ERPs were recorded during viewing of backward-masked neutral, fearful and happy faces presented under two conditions: subliminal (16 ms, below the level of visual conscious awareness and supraliminal (166 ms, above the time required for visual conscious awareness. Individuals with low and high AQ differed in the processing of subliminal faces, with the low AQ group showing an enhanced N2 amplitude for subliminal happy faces. Some group differences were found in the condition effects, with the Low AQ showing shorter frontal P3b and N4 latencies for subliminal vs. supraliminal condition. Although results did not show any group differences on the face-specific N170 component, there were shorter N170 latencies for supraliminal vs. subliminal conditions across groups. The results observed on the N2, showing group differences in subliminal emotion processing, suggest that decreased sensitivity to the reward value of social stimuli is a common feature both of people with ASD as well as people with high autistic traits from the normal population.

  1. Electrophysiological Correlates of Subliminal Perception of Facial Expressions in Individuals with Autistic Traits: A Backward Masking Study.

    Science.gov (United States)

    Vukusic, Svjetlana; Ciorciari, Joseph; Crewther, David P

    2017-01-01

    People with Autism spectrum disorder (ASD) show difficulty in social communication, especially in the rapid assessment of emotion in faces. This study examined the processing of emotional faces in typically developing adults with high and low levels of autistic traits (measured using the Autism Spectrum Quotient-AQ). Event-related potentials (ERPs) were recorded during viewing of backward-masked neutral, fearful and happy faces presented under two conditions: subliminal (16 ms, below the level of visual conscious awareness) and supraliminal (166 ms, above the time required for visual conscious awareness). Individuals with low and high AQ differed in the processing of subliminal faces, with the low AQ group showing an enhanced N2 amplitude for subliminal happy faces. Some group differences were found in the condition effects, with the Low AQ showing shorter frontal P3b and N4 latencies for subliminal vs. supraliminal condition. Although results did not show any group differences on the face-specific N170 component, there were shorter N170 latencies for supraliminal vs. subliminal conditions across groups. The results observed on the N2, showing group differences in subliminal emotion processing, suggest that decreased sensitivity to the reward value of social stimuli is a common feature both of people with ASD as well as people with high autistic traits from the normal population.

  2. An electrophysiological study of the object-based correspondence effect: is the effect triggered by an intended grasping action?

    Science.gov (United States)

    Lien, Mei-Ching; Jardin, Elliott; Proctor, Robert W

    2013-11-01

    We examined Goslin, Dixon, Fischer, Cangelosi, and Ellis's (Psychological Science 23:152-157, 2012) claim that the object-based correspondence effect (i.e., faster keypress responses when the orientation of an object's graspable part corresponds with the response location than when it does not) is the result of object-based attention (vision-action binding). In Experiment 1, participants determined the category of a centrally located object (kitchen utensil vs. tool), as in Goslin et al.'s study. The handle orientation (left vs. right) did or did not correspond with the response location (left vs. right). We found no correspondence effect on the response times (RTs) for either category. The effect was also not evident in the P1 and N1 components of the event-related potentials, which are thought to reflect the allocation of early visual attention. This finding was replicated in Experiment 2 for centrally located objects, even when the object was presented 45 times (33 more times than in Exp. 1). Critically, the correspondence effects on RTs, P1s, and N1s emerged only when the object was presented peripherally, so that the object handle was clearly located to the left or right of fixation. Experiment 3 provided further evidence that the effect was observed only for the base-centered objects, in which the handle was clearly positioned to the left or right of center. These findings contradict those of Goslin et al. and provide no evidence that an intended grasping action modulates visual attention. Instead, the findings support the spatial-coding account of the object-based correspondence effect.

  3. Electrophysiological studies of the feasibility of suprachoroidal-transretinal stimulation for artificial vision in normal and RCS rats.

    Science.gov (United States)

    Kanda, Hiroyuki; Morimoto, Takeshi; Fujikado, Takashi; Tano, Yasuo; Fukuda, Yutaka; Sawai, Hajime

    2004-02-01

    Assessment of a novel method of retinal stimulation, known as suprachoroidal-transretinal stimulation (STS), which was designed to minimize insult to the retina by implantation of stimulating electrodes for artificial vision. In 17 normal hooded rats and 12 Royal College of Surgeons (RCS) rats, a small area of the retina was focally stimulated with electric currents through an anode placed on the fenestrated sclera and a cathode inserted into the vitreous chamber. Evoked potentials (EPs) in response to STS were recorded from the surface of the superior colliculus (SC) with a silver-ball electrode, and their physiological properties and localization were studied. In both normal and RCS rats, STS elicited triphasic EPs that were vastly diminished by changing polarity of stimulating electrodes and abolished by transecting the optic nerve. The threshold intensity (C) of the EP response to STS was approximately 7.2 +/- 2.8 nC in normal and 12.9 +/- 7.7 nC in RCS rats. The responses to minimal STS were localized in an area on the SC surface measuring 0.12 +/- 0.07 mm(2) in normal rats and 0.24 +/- 0.12 mm(2) in RCS rats. The responsive area corresponded retinotopically to the retinal region immediately beneath the anodic stimulating electrode. STS is less invasive in the retina than stimulation through epiretinal or subretinal implants. STS can generate focal excitation in retinal ganglion cells in normal animals and in those with degenerated photoreceptors, which suggests that this method of retinal stimulation is suitable for artificial vision.

  4. [11 C]Rhodamine-123: Synthesis and biodistribution in rodents

    International Nuclear Information System (INIS)

    Bao Xiaofeng; Lu Shuiyu; Liow, Jeih-San; Morse, Cheryl L.; Anderson, Kacey B.; Zoghbi, Sami S.; Innis, Robert B.; Pike, Victor W.

    2012-01-01

    Introduction: Rhodamine-123 is a known substrate for the efflux transporter, P-glycoprotein (P-gp). We wished to assess whether rhodamine-123 might serve as a useful substrate for developing probes for imaging efflux transporters in vivo with positron emission tomography (PET). For this purpose, we aimed to label rhodamine-123 with carbon-11 (t 1/2 = 20.4 min) and to study its biodistribution in rodents. Methods: [ 11 C]Rhodamine-123 was prepared by treating rhodamine-110 (desmethyl-rhodamine-123) with [ 11 C]methyl iodide. The biodistribution of this radiotracer was studied with PET in wild-type mice and rats, in efflux transporter knockout mice, in wild-type rats pretreated with DCPQ (an inhibitor of P-gp) or with cimetidine (an inhibitor of organic cation transporters; OCT), and in P-gp knockout mice pretreated with cimetidine. Unchanged radiotracer in forebrain, plasma and peripheral tissues was also measured ex vivo at 30 min after radiotracer administration to wild-type and efflux transporter knockout rodents. Results: [ 11 C]Rhodamine-123 was obtained in 4.4% decay-corrected radiochemical yield from cyclotron-produced [ 11 C]carbon dioxide. After intravenous administration of [ 11 C]rhodamine-123 to wild-type rodents, PET and ex vivo measurements showed radioactivity uptake was very low in brain, but relatively high in some other organs such as heart, and especially liver and kidney. Inhibition of P-gp increased uptake in brain, heart, kidney and liver, but only by up to twofold. Secretion of radioactivity from kidney was markedly reduced by OCT knockout or pretreatment with cimetidine. Conclusions: [ 11 C]Rhodamine-123 was unpromising as a PET probe for P-gp function and appears to be a strong substrate of OCT in kidney. Cimetidine appears effective for blocking OCT in kidney in vivo.

  5. The Consistency Between Clinical and Electrophysiological Diagnoses

    Directory of Open Access Journals (Sweden)

    Esra E. Okuyucu

    2009-09-01

    Full Text Available OBJECTIVE: The aim of this study was to provide information concerning the impact of electrophysiological tests in the clinical management and diagnosis of patients, and to evaluate the consistency between referring clinical diagnoses and electrophysiological diagnoses. METHODS: The study included 957 patients referred to the electroneuromyography (ENMG laboratory from different clinics with different clinical diagnoses in 2008. Demographic data, referring clinical diagnoses, the clinics where the requests wanted, and diagnoses after ENMG testing were recorded and statistically evaluated. RESULTS: In all, 957 patients [644 (67.3% female and 313 (32.7% male] were included in the study. Mean age of the patients was 45.40 ± 14.54 years. ENMG requests were made by different specialists; 578 (60.4% patients were referred by neurologists, 122 (12.8% by orthopedics, 140 (14.6% by neurosurgeons, and 117 (12.2% by physical treatment and rehabilitation departments. According to the results of ENMG testing, 513 (53.6% patients’ referrals were related to their referral diagnosis, whereas 397 (41.5% patients had normal ENMG test results, and 47 (4.9% patients had a diagnosis that differed from the referring diagnosis. Among the relation between the referral diagnosis and electrophysiological diagnosis according to the clinics where the requests were made, there was no statistical difference (p= 0.794, but there were statistically significant differences between the support of different clinical diagnoses, such as carpal tunnel syndrome, polyneuropathy, radiculopathy-plexopathy, entrapment neuropathy, and myopathy based on ENMG test results (p< 0.001. CONCLUSION: ENMG is a frequently used neurological examination. As such, referrals for ENMG can be made to either support the referring diagnosis or to exclude other diagnoses. This may explain the inconsistency between clinical referring diagnoses and diagnoses following ENMG

  6. Optimizing Nanoelectrode Arrays for Scalable Intracellular Electrophysiology.

    Science.gov (United States)

    Abbott, Jeffrey; Ye, Tianyang; Ham, Donhee; Park, Hongkun

    2018-03-20

    Electrode technology for electrophysiology has a long history of innovation, with some decisive steps including the development of the voltage-clamp measurement technique by Hodgkin and Huxley in the 1940s and the invention of the patch clamp electrode by Neher and Sakmann in the 1970s. The high-precision intracellular recording enabled by the patch clamp electrode has since been a gold standard in studying the fundamental cellular processes underlying the electrical activities of neurons and other excitable cells. One logical next step would then be to parallelize these intracellular electrodes, since simultaneous intracellular recording from a large number of cells will benefit the study of complex neuronal networks and will increase the throughput of electrophysiological screening from basic neurobiology laboratories to the pharmaceutical industry. Patch clamp electrodes, however, are not built for parallelization; as for now, only ∼10 patch measurements in parallel are possible. It has long been envisioned that nanoscale electrodes may help meet this challenge. First, nanoscale electrodes were shown to enable intracellular access. Second, because their size scale is within the normal reach of the standard top-down fabrication, the nanoelectrodes can be scaled into a large array for parallelization. Third, such a nanoelectrode array can be monolithically integrated with complementary metal-oxide semiconductor (CMOS) electronics to facilitate the large array operation and the recording of the signals from a massive number of cells. These are some of the central ideas that have motivated the research activity into nanoelectrode electrophysiology, and these past years have seen fruitful developments. This Account aims to synthesize these findings so as to provide a useful reference. Summing up from the recent studies, we will first elucidate the morphology and associated electrical properties of the interface between a nanoelectrode and a cellular membrane

  7. Osteoarthritis-dependent changes in antinociceptive action of Nav1.7 and Nav1.8 sodium channel blockers: An in vivo electrophysiological study in the rat.

    Science.gov (United States)

    Rahman, W; Dickenson, A H

    2015-06-04

    Voltage-gated sodium channel blockers are not traditionally recommended for osteoarthritis (OA) pain therapy, but given the large peripheral drive that follows OA development there is a rationale for their use. Using a rat model of monosodium iodoacetate (MIA)-induced OA we used in vivo electrophysiology to assess the effects of the Nav1.7- and Nav1.8-selective antagonists, ProTxII and A-803467 respectively, on the evoked activity of spinal dorsal horn neurons in response to electrical, mechanical and thermal stimuli applied to the peripheral receptive field. These studies allow examination of the roles of these channels in suprathreshold stimuli, not amenable to behavioral threshold measures. Spinal administration of ProTxII significantly reduced neuronal responses evoked by mechanical punctate (von Frey (vF) 8-60g) and noxious thermal (45 and 48°C) stimuli in MIA rats only. A-803467 significantly inhibited neuronal responses evoked by vF 8-60g and 48°C heat after spinal administration; significantly inhibited responses evoked by brush, vFs 26-60g and 40-48°C stimuli after systemic administration; significantly inhibited the electrically evoked Aδ-, C-fiber, post-discharge, Input and wind-up responses and the brush, vFs 8-60g and 45-48°C evoked neuronal responses after intra plantar injection in the MIA group. In comparison A-803467 effects in the sham group were minimal and included a reduction of the neuronal response evoked by vF 60g and 45°C heat stimulation after spinal administration, no effect after systemic administration and an inhibition of the evoked response to 45°C heat after intra plantar injection only. The observed selective inhibitory effect of ProTxII and A-803467 for the MIA-treated group suggests an increased role of Nav1.7 and 1.8 within nociceptive pathways in the arthritic condition, located at peripheral and central sites. These findings demonstrate the importance of, and add to, the mechanistic understanding of these channels in

  8. Labeling of vasoactive intestinal peptide (VIP) and VIP 10-28 fragment with radioiodine by direct method. Comparative study of the kinetics biodistribution and affinity for neuroendocrine tumor cells

    International Nuclear Information System (INIS)

    Colturato, Maria Tereza

    2005-01-01

    mixture (simple purification) and to produce the radiopharmaceutical with high specific activity (complex purification and HPLC), were both efficient in the separation of the species in the reaction mixtures, as demonstrated by quality control procedures. Biological distribution studies were accomplished by venous administration of the radiopharmaceuticals in laboratory animals: biodistribution study of [ 131 I]VIP and [ 131 I]VIP 10-28 in normal Swiss mice, [ 131 I]VIP not purified and purified in Swiss mice with tumor and [ 131 I]VIP and [ 131 I]VIP 10-28 in Nude mice with tumor, scintigraphic images of [ 131/123 I]VIP and [ 123 I]VIP 10-28 in Swiss and Nude mice and Wistar rats with tumor. In vitro studies were accomplished to determine the percentage of [ 131 I]VIP and [ 131 I]VIP 10-28 bound to plasmatic proteins, stability study of [ 131 I]VIP and [ 131 I]VIP 10-28 in human plasma and the affinity and internalization of [ 131 I]VIP and [ 131 I]VIP 10-28 by tumour adenocarcinoma cells of human rectal colon (HT-29). All biological distribution studies demonstrated that both [ 131/123 I]VIP and [ 131/123 I]VIP 10-28 showed fast blood clearance, low renal and liver uptake, relative uptake in thyroid, showing in vivo dehalogenation and good uptake in tumour. Comparative biological distribution of the radiopharmaceuticals showed high uptake in the stomach for both peptides. The blood clearance of the fragment was slower, and influences the visualization of the tumour mass. The radiopharmaceuticals, [ 123 I]VIP and [ 123 I]VIP 10-28, were obtained with high radiochemical purity, but with low radiochemical yield when comparing with labeling procedures using iodine-131. Quality control assays of [ 123 I]Na indicated that the presence of radiochemical and radionuclide impurities influenced on labeling results. (author)

  9. Comparison of therapeutic efficacy and biodistribution of 213Bi- and 211At-labeled monoclonal antibody MX35 in an ovarian cancer model

    DEFF Research Database (Denmark)

    Gustafsson, Anna M E; Bäck, Tom; Elgqvist, Jörgen

    2012-01-01

    The purpose of this study was to compare the therapeutic efficacy and biodistribution of the monoclonal antibody MX35 labeled with either (213)Bi or (211)At, both α-emitters, in an ovarian cancer model.......The purpose of this study was to compare the therapeutic efficacy and biodistribution of the monoclonal antibody MX35 labeled with either (213)Bi or (211)At, both α-emitters, in an ovarian cancer model....

  10. Effect of iron deficiency anemia on the biodistribution of 99mTc radiopharmaceuticals

    International Nuclear Information System (INIS)

    Calmanovici, Gabriela P.; Salgueiro, Maria J.; Janjetic, Mariana A.; Leonardi, Natalia M.; Boccio, Jose R.; Zubillaga, Marcela B.

    2006-01-01

    The distribution of colloids and labeled cells in organs is influenced by their intrinsic properties and by the state of the investigated subject. Iron deficiency remains an unsolved nutritional problem all over the world; one of its severe consequences is anemia. Because iron metabolism principally takes place in the liver, spleen, bone marrow, skeletal muscle and blood, we studied the effect of iron deficiency anemia on the biodistribution of 99m Tc phytate, 99m Tc gelatin colloid and 99m Tc RBC (red blood cells labeled with 99m Tc). Our results show that iron deficiency anemia modifies the pattern of biodistribution of the two colloids assayed. However, this behavior is different for both of them. This work contributes to studies that kinetically and statistically establish that iron deficiency anemia induces a significant inversion in the spleen-liver activity relationship when centellographic studies are performed with colloids such as 99m Tc phytate

  11. Electrophysiological Evidence in Schizophrenia in Relation to Treatment Response

    Directory of Open Access Journals (Sweden)

    Kazuki Sueyoshi

    2018-06-01

    Full Text Available Several domains of cognitive function, e.g., verbal memory, information processing, fluency, attention, and executive function are impaired in patients with schizophrenia. Cognitive impairments in schizophrenia have attracted interests as a treatment target, because they are considered to greatly affect functional outcome. Electrophysiological markers, including electroencephalogram (EEG, particularly, event-related potentials, have contributed to psychiatric research and clinical practice. In this review, we provide a summary of studies relating electrophysiological findings to cognitive performance in schizophrenia. Electrophysiological indices may provide an objective marker of cognitive processes, contributing to the development of effective interventions to improve cognitive and social outcomes. Further efforts to understand biological mechanisms of cognitive disturbances, and develop effective therapeutics are warranted.

  12. The electrophysiology of introspection

    DEFF Research Database (Denmark)

    Overgaard, Morten; Koivisto, Mika; Sørensen, Thomas Alrik

    2006-01-01

    To study whether the distinction between introspective and non-introspective states of mind is an empirical reality or merely a conceptual distinction, we measured event-related potentials (ERPs) elicited in introspective and non-introspective instruction conditions while the observers were tryin...... to detect the presence of a masked stimulus. The ERPs indicated measurable differences related to introspection in both preconscious and conscious processes. Our data support the hypothesis that introspective states empirically differ from non-introspective states....

  13. Conductive Hearing Loss during Infancy: Effects on Later Auditory Brain Stem Electrophysiology.

    Science.gov (United States)

    Gunnarson, Adele D.; Finitzo, Terese

    1991-01-01

    Long-term effects on auditory electrophysiology from early fluctuating hearing loss were studied in 27 children, aged 5 to 7 years, who had been evaluated originally in infancy. Findings suggested that early fluctuating hearing loss disrupts later auditory brain stem electrophysiology. (Author/DB)

  14. Biodistribution parameters and radiation absorbed dose estimates for radiolabeled human low density lipoprotein

    International Nuclear Information System (INIS)

    Hay, R.V.; Ryan, J.W.; Williams, K.A.; Atcher, R.W.; Brechbiel, M.W.; Gansow, O.A.; Fleming, R.M.; Stark, V.J.; Lathrop, K.A.; Harper, P.V.

    1992-01-01

    The authors propose a model to generate radiation absorbed dose estimates for radiolabeled low density lipoprotein (LDL), based upon eight studies of LDL biodistribution in three adult human subjects. Autologous plasma LDL was labeled with Tc-99m, I-123, or In-111 and injected intravenously. Biodistribution of each LDL derivative was monitored by quantitative analysis of scintigrams and direct counting of excreta and of serial blood samples. Assuming that transhepatic flux accounts for the majority of LDL clearance from the bloodstream, they obtained values of cumulated activity (A) and of mean dose per unit administered activity (D) for each study. In each case highest D values were calculated for liver, with mean doses of 5 rads estimated at injected activities of 27 mCi, 9 mCi, and 0.9 mCi for Tc-99m-LDL, I-123-LDL, and In-111-LDL, respectively

  15. Pharmacokinetics and Biodistribution of the Illegal Food Colorant Rhodamine B in Rats.

    Science.gov (United States)

    Cheng, Yung-Yi; Tsai, Tung-Hu

    2017-02-08

    The International Agency for Research on Cancer (IARC) demonstrated rhodamine B as a potential carcinogen in 1978. Nevertheless, rhodamine B has been illegally used as a colorant in food in many countries. Few pharmacokinetic and toxicological investigations have been performed since the first pharmacokinetic study on rhodamine B in 1961. The aims of this study were to develop a simple and sensitive high-performance liquid chromatography method with fluorescence detection for the quantitative detection of rhodamine B in the plasma and organs of rats and to estimate its pharmacokinetics and biodistribution. The results demonstrated that the oral bioavailabilities of rhodamine B were 28.3 and 9.8% for the low-dose and high-dose exposures, respectively. Furthermore, rhodamine B was highly accumulated in the liver and, to a lesser extent, the kidney, but was undetectable in the brain. These results provide useful information for improving the pharmacokinetics and biodistribution of rhodamine B, supporting additional food safety evaluations.

  16. Fluorescent Labeling and Biodistribution of Latex Nanoparticles Formed by Surfactant-Free RAFT Emulsion Polymerization.

    Science.gov (United States)

    Poon, Cheuk Ka; Tang, Owen; Chen, Xin-Ming; Kim, Byung; Hartlieb, Matthias; Pollock, Carol A; Hawkett, Brian S; Perrier, Sébastien

    2017-10-01

    The authors report the preparation of a novel range of functional polyacrylamide stabilized polystyrene nanoparticles, obtained by surfactant-free reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization, their fluorescent tagging, cellular uptake, and biodistribution. The authors show the versatility of the RAFT emulsion process for the design of functional nanoparticles of well-defined size that can be used as drug delivery vectors. Functionalization with a fluorescent tag offers a useful visualization tool for tracing, localization, and clearance studies of these carriers in biological models. The studies are carried out by labeling the sterically stabilized latex particles chemically with rhodamine B. The fluorescent particles are incubated in a healthy human renal proximal tubular cell line model, and intravenously injected into a mouse model. Cellular localization and biodistribution of these particles on the biological models are explored. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Pelvic floor electrophysiology in spinal cord injury.

    Science.gov (United States)

    Tankisi, H; Pugdahl, K; Rasmussen, M M; Clemmensen, D; Rawashdeh, Y F; Christensen, P; Krogh, K; Fuglsang-Frederiksen, A

    2016-05-01

    The study aimed to investigate sacral peripheral nerve function and continuity of pudendal nerve in patients with chronic spinal cord injury (SCI) using pelvic floor electrophysiological tests. Twelve patients with low cervical or thoracic SCI were prospectively included. Quantitative external anal sphincter (EAS) muscle electromyography (EMG), pudendal nerve terminal motor latency (PNTML) testing, bulbocavernosus reflex (BCR) testing and pudendal short-latency somatosensory-evoked potential (SEP) measurement were performed. In EAS muscle EMG, two patients had abnormal increased spontaneous activity and seven prolonged motor unit potential duration. PNTML was normal in 10 patients. BCR was present with normal latency in 11 patients and with prolonged latency in one. The second component of BCR could be recorded in four patients. SEPs showed absent cortical responses in 11 patients and normal latency in one. Pudendal nerve and sacral lower motor neuron involvement are significantly associated with chronic SCI, most prominently in EAS muscle EMG. The frequent finding of normal PNTML latencies supports earlier concerns on the utility of this test; however, BCR and pudendal SEPs may have clinical relevance. As intact peripheral nerves including pudendal nerve are essential for efficient supportive therapies, pelvic floor electrophysiological testing prior to these interventions is highly recommended. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  18. Radiolabeling of codeine with 131I and its biodistribution in rats

    International Nuclear Information System (INIS)

    Enginar, H.

    2009-01-01

    Codeine which was extracted from dry capsules of the opium poppy (Papaver somniferum) was purified by HPLC (High Performance Liquid Chromatography) and characterized by NMR (Nuclear Magnetic Resonance) and IR (Infrared) spectroscopy techniques. The purified compound was labeled with 131 I and biodistribution studies were performed in rats. Radioiodinated codeine distributed uniformly in the cerebellum, m.pons, striatum and hypothalamus while the other branch of brain and Stomach, urinary bladder, and small intestine uptakes were significantly higher than other tissues. (author)

  19. Electrophysiological evidence for phenomenal consciousness.

    Science.gov (United States)

    Revonsuo, Antti; Koivisto, Mika

    2010-09-01

    Abstract Recent evidence from event-related brain potentials (ERPs) lends support to two central theses in Lamme's theory. The earliest ERP correlate of visual consciousness appears over posterior visual cortex around 100-200 ms after stimulus onset. Its scalp topography and time window are consistent with recurrent processing in the visual cortex. This electrophysiological correlate of visual consciousness is mostly independent of later ERPs reflecting selective attention and working memory functions. Overall, the ERP evidence supports the view that phenomenal consciousness of a visual stimulus emerges earlier than access consciousness, and that attention and awareness are served by distinct neural processes.

  20. PERIPHERAL NEUROPATHY ELECTROPHYSIOLOGICAL SCREENING IN CHILDREN WITH CELIAC DISEASE

    Directory of Open Access Journals (Sweden)

    Şedat IŞIKAY

    2015-06-01

    Full Text Available Background The involvement of the peripheral nervous system in children with celiac disease is particularly rare. Objective The aim of this study was to assess the need for neurophysiological testing in celiac disease patients without neurological symptoms in order to detect early subclinical neuropathy and its possible correlations with clinical and demographic characteristics. Methods Two hundred and twenty consecutive children with celiac disease were screened for neurological symptoms and signs, and those without symptoms or signs were included. Also, patients with comorbidities associated with peripheral neuropathy or a history of neurological disease were excluded. The remaining 167 asymptomatic patients as well as 100 control cases were tested electro-physiologically for peripheral nervous system diseases. Motor nerve conduction studies, including F-waves, were performed for the median, ulnar, peroneal, and tibial nerves, and sensory nerve conduction studies were performed for the median, ulnar, and sural nerves with H reflex of the soleus muscle unilaterally. All studies were carried out using surface recording electrodes. Normative values established in our laboratory were used. Results Evidence for subclinical neuropathy was not determined with electrophysiological studies in any of the participants. Conclusion In this highly selective celiac disease group without any signs, symptoms as well as the predisposing factors for polyneuropathy, we did not determine any cases with neuropathy. With these results we can conclude that in asymptomatic cases with celiac disease electrophysiological studies are not necessary. However, larger studies with the electrophysiological studies performed at different stages of disease at follow-ups are warranted.

  1. Electrophysiological assessment in patients with Mobius syndrome and clumsiness.

    NARCIS (Netherlands)

    Verzijl, H.T.F.M.; Padberg, G.W.A.M.; Zwarts, M.J.

    2005-01-01

    The authors studied the nature of clumsiness in Mobius syndrome in terms of motor or sensory deficits, and sought to clarify the pathophysiological mechanism of the syndrome. Standardized electrophysiologic studies were conducted, with special emphasis on the long motor and sensory tracts and

  2. Altered [99mTc]Tc-MDP biodistribution from neutron activation sourced 99Mo.

    Science.gov (United States)

    Demeter, Sandor; Szweda, Roman; Patterson, Judy; Grigoryan, Marine

    2018-01-01

    Given potential worldwide shortages of fission sourced 99 Mo/ 99m Tc medical isotopes there is increasing interest in alternate production strategies. A neutron activated 99 Mo source was utilized in a single center phase III open label study comparing 99m Tc, as 99m Tc Methylene Diphosphonate ([ 99m Tc]Tc-MDP), obtained from solvent generator separation of neutron activation produced 99 Mo, versus nuclear reactor produced 99 Mo (e.g., fission sourced) in oncology patients for which an [ 99m Tc]Tc-MDP bone scan would normally have been indicated. Despite the investigational [ 99m Tc]Tc-MDP passing all standard, and above standard of care, quality assurance tests, which would normally be sufficient to allow human administration, there was altered biodistribution which could lead to erroneous clinical interpretation. The cause of the altered biodistribution remains unknown and requires further research.

  3. Validation of 18FDG biodistribution data in healthy mice obtained with G.E. LABPET4

    International Nuclear Information System (INIS)

    Rocha, Adriana Marcia Guimaraes; Mendes, Bruno Melo; Malamut, Carlos; Silva, Juliana Batista da; Campos, Danielle Cunha; Santos, Priscilla Figueiredo

    2013-01-01

    The aim of this study is to validate biodistribution data obtained with CDTN's MicroPET. To achieve this goal, correction and image acquisition procedures were established. 1 '8FDG dynamic images of 90 minutes were obtained following these procedures for Swiss healthy mice. Biodistribution data obtained after quantification of acquired images were compared with data available in literature. Considering the uptake time of 60 minutes and similar animal handling, data obtained in this work showed a satisfactory agreement with reference data. Some evaluated organs/tissues showed high interindividual variability. These findings are consistent with those observed in reference literature. However, improvements in VOI positioning VOI technique as well as increasing the number of animals (n) per group can minimize this problem. (author)

  4. Biodistribution of the radiopharmaceutical sodium pertechnetate after biliopancreatic bypass with a duodenal switch

    International Nuclear Information System (INIS)

    Araujo-Filho, Irami; Rego, Amalia Cinthia Meneses; Brandao-Neto, Jose; Villarim-Neto, Arthur; Egito, Eryvaldo Socrates Tabosa; Azevedo, Italo Medeiros; Medeiros, Aldo Cunha

    2007-01-01

    Study with the purpose to examine the effects of duodenal switch (DS), regularly performed in morbidly obese patients, on biodistribution of sodium pertechnetate in several organs of rats. There was no early or late mortality in either rats groups. The values of percent radioactivity per gram of tissue (%ATI/g), showed no significant difference in liver, stomach, small bowel, duodenum, kidney, heart, bladder, bone and brain, when compared the DS rats with sham and controls rats. A postoperative significant increase (p<0.05) in mean %ATI/g levels was observed in spleen, pancreas and muscle in group DS rats, as compared to group S and C rats. In the lung there was an increase and in thyroid a decrease in mean %ATI/g of DS rats, when compared to sham rats (p<0.05). In conclusion, the biliopancreatic diversion with duodenal switch in rats modified the biodistribution of sodium pertechnetate in thyroid, lung, pancreas, spleen and muscle. (author)

  5. Biodistribution of the radiopharmaceutical sodium pertechnetate after biliopancreatic bypass with a duodenal switch

    Energy Technology Data Exchange (ETDEWEB)

    Araujo-Filho, Irami; Rego, Amalia Cinthia Meneses; Brandao-Neto, Jose; Villarim-Neto, Arthur; Egito, Eryvaldo Socrates Tabosa; Azevedo, Italo Medeiros; Medeiros, Aldo Cunha [Universidade Federal do Rio Grande do Norte, Natal, RN (Brazil). Programa de Pos-graduacao em Ciencias da Saude]. E-mail: aldo@ufrnet.br

    2007-09-15

    Study with the purpose to examine the effects of duodenal switch (DS), regularly performed in morbidly obese patients, on biodistribution of sodium pertechnetate in several organs of rats. There was no early or late mortality in either rats groups. The values of percent radioactivity per gram of tissue (%ATI/g), showed no significant difference in liver, stomach, small bowel, duodenum, kidney, heart, bladder, bone and brain, when compared the DS rats with sham and controls rats. A postoperative significant increase (p<0.05) in mean %ATI/g levels was observed in spleen, pancreas and muscle in group DS rats, as compared to group S and C rats. In the lung there was an increase and in thyroid a decrease in mean %ATI/g of DS rats, when compared to sham rats (p<0.05). In conclusion, the biliopancreatic diversion with duodenal switch in rats modified the biodistribution of sodium pertechnetate in thyroid, lung, pancreas, spleen and muscle. (author)

  6. Preparation of 177Lu-DTPA-BIS-BIOTIN and biodistribution evaluation in normal mice

    International Nuclear Information System (INIS)

    Deng Xinrong; Luo Zhifu; Du Jin

    2010-01-01

    The labeling method for 177 Lu-DTPA-BIS-BIOTIN was established, and the biodistribution of 177 Lu-DTPA-BIS-BIOTIN in normal mice was carried out as well. Under the optimal experimental condition (DTPA-BIS-BIOTIN 25 μg, pH=4.5 reacting at 80 degree C for 20 min), the labeling yield of 177 Lu-DTPA-BIS-BIOTIN is more than 99.0%. 177 Lu-DTPA-BIS-BIOTIN shows pretty good in vitro stability. The biodistribution of 177 Lu-DTPA-BIS-BIOTIN in normal mice shows a rapid blood clearance. The uptake of 177 Lu-DTPA-BIS-BIOTIN is mainly accumulated in liver, spleen and kidney. 177 Lu-DTPA-BIS-BIOTIN is excreted by kidney. The results provide the basis for further study on 177 Lu-DTPA-BIS-BIOTIN used in pretargeted radioimage and radiotherapy of cancer. (authors)

  7. The biodistribution and kinetics of the 153Sm labelled avidin, streptavidin and biotin

    International Nuclear Information System (INIS)

    Li Guiping; Zhu Chengmo; Jiang Xufeng; Feng Guowei; Zhang Shengguo

    1999-01-01

    Due to the high affinity of biotin to Av or SA. The authors labelled a biotin derivative (DTPA-biotin) with 153 Sm and then bound this 153 Sm labelled DTPA-biotin to Av or SA. The in vivo kinetics and biodistribution of 153 Sm labelled Av, SA and DTPA-biotin were studied in the rat and mice. The results demonstrated that 153 Sm-Av cleared from the blood rapidly with high liver and renal uptake; 153 Sm-SA cleared from blood slowly with high retention in liver, spleen and kidney, whereas 153 Sm metabolize more fast, and excreted mainly through the kidney. Thereby, the biodistribution difference of SA and Av mentioned above provided an experimental basis for the selection of different components of A-V system in pre-targeting radio-immuno imaging and radioimmunotherapy

  8. A Potential Dubin-Johnson Syndrome Imaging Agent: Synthesis, Biodistribution, and MicroPET Imaging

    Directory of Open Access Journals (Sweden)

    Jeongsoo Yoo

    2005-01-01

    Full Text Available Dubin-Johnson syndrome (DJS is caused by a deficiency of the human canalicular multispecific organic anion transporter (cMOAT. A new lipophilic copper-64 complex of 1,4,7-tris(carboxymethyl-10-(tetradecyl-1,4,7,10-tetraazadodecane (5 was prepared and evaluated for potential as a diagnostic tool for DJS. The prepared ligand was labeled with 64Cu citrate in high radiochemical purity. In vivo uptake and clearance of the complex was determined through biodistribution studies using normal Sprague-Dawley rats and mutant cMOAT-deficient (TR− rats. In normal rats, the radioactive copper complex was cleared quickly from the body exclusively through the hepatic pathway. The 64Cu complex was taken up rapidly by the liver and quickly excreted into the small intestine and then the upper large intestine, whereas < 1% ID/organ was found in the kidney at all time points post injection. Whereas activity was accumulated continuously in the liver of TR− rats, it was not excreted into the small intestine. MicroPET studies of normal and TR rats were consistent with biodistribution data and showed dramatically different images. This study strongly suggests that cMOAT is involved in excretion of 64Cu-5. The significant difference between the biodistribution data and microPET images of the normal and TR− rats demonstrates that this new 64Cu complex may allow noninvasive diagnosis of DJS in humans.

  9. Samarium oxide as a radiotracer to evaluate the in vivo biodistribution of PLGA nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Mandiwana, Vusani, E-mail: VMandiwana@csir.co.za; Kalombo, Lonji, E-mail: LKalombo@csir.co.za [Centre of Polymers and Composites, CSIR (South Africa); Venter, Kobus, E-mail: Kobus.Venter@mrc.ac.za [South African Medical Research Council (South Africa); Sathekge, Mike, E-mail: Mike.Sathekge@up.ac.za [University of Pretoria and Steve Biko Academic Hospital, Department of Nuclear Medicine (South Africa); Grobler, Anne, E-mail: Anne.Grobler@nwu.ac.za; Zeevaart, Jan Rijn, E-mail: zeevaart@necsa.co.za [North-West University, DST/NWU Preclinical Drug Development Platform (South Africa)

    2015-09-15

    Developing nanoparticulate delivery systems that will allow easy movement and localization of a drug to the target tissue and provide more controlled release of the drug in vivo is a challenge in nanomedicine. The aim of this study was to evaluate the biodistribution of poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles containing samarium-153 oxide ([{sup 153}Sm]Sm{sub 2}O{sub 3}) in vivo to prove that orally administered nanoparticles alter the biodistribution of a drug. These were then activated in a nuclear reactor to produce radioactive {sup 153}Sm-loaded-PLGA nanoparticles. The nanoparticles were characterized for size, zeta potential, and morphology. The nanoparticles were orally and intravenously (IV) administered to rats in order to trace their uptake through imaging and biodistribution studies. The {sup 153}Sm-loaded-PLGA nanoparticles had an average size of 281 ± 6.3 nm and a PDI average of 0.22. The zeta potential ranged between 5 and 20 mV. The [{sup 153}Sm]Sm{sub 2}O{sub 3} loaded PLGA nanoparticles, orally administered were distributed to most organs at low levels, indicating that there was absorption of nanoparticles. While the IV injected [{sup 153}Sm]Sm{sub 2}O{sub 3}-loaded PLGA nanoparticles exhibited the highest localization of nanoparticles in the spleen (8.63 %ID/g) and liver (3.07 %ID/g), confirming that nanoparticles are rapidly removed from the blood by the RES, leading to rapid uptake in the liver and spleen. From the biodistribution data obtained, it is clear that polymeric nanoscale delivery systems would be suitable for improving permeability and thus the bioavailability of therapeutic compounds.

  10. TISCON, a BASIC computer program for the calculation of the biodistribution of radionuclide-labelled drugs in rats and mice

    International Nuclear Information System (INIS)

    Maddalena, D.J.

    1983-09-01

    Animal biodistribution studies on radionuclide-labelled drugs are labour-intensive and time-consuming. A method for rapidly carrying out these studies on rats and mice is presented. An interactive computer program, written in BASIC, is used to calculate parameters of interest, such as per cent injected dose (%ID),%ID per gram and target to non-target ratios

  11. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting

    Directory of Open Access Journals (Sweden)

    Oscar P. B. Wiklander

    2015-04-01

    Full Text Available Extracellular vesicles (EVs have emerged as important mediators of intercellular communication in a diverse range of biological processes. For future therapeutic applications and for EV biology research in general, understanding the in vivo fate of EVs is of utmost importance. Here we studied biodistribution of EVs in mice after systemic delivery. EVs were isolated from 3 different mouse cell sources, including dendritic cells (DCs derived from bone marrow, and labelled with a near-infrared lipophilic dye. Xenotransplantation of EVs was further carried out for cross-species comparison. The reliability of the labelling technique was confirmed by sucrose gradient fractionation, organ perfusion and further supported by immunohistochemical staining using CD63-EGFP probed vesicles. While vesicles accumulated mainly in liver, spleen, gastrointestinal tract and lungs, differences related to EV cell origin were detected. EVs accumulated in the tumour tissue of tumour-bearing mice and, after introduction of the rabies virus glycoprotein-targeting moiety, they were found more readily in acetylcholine-receptor-rich organs. In addition, the route of administration and the dose of injected EVs influenced the biodistribution pattern. This is the first extensive biodistribution investigation of EVs comparing the impact of several different variables, the results of which have implications for the design and feasibility of therapeutic studies using EVs.

  12. Clinical feasibility of {sup 90}Y digital PET/CT for imaging microsphere biodistribution following radioembolization

    Energy Technology Data Exchange (ETDEWEB)

    Wright, Chadwick L.; Binzel, Katherine; Zhang, Jun; Knopp, Michael V. [The Ohio State University Wexner Medical Center, Wright Center of Innovation in Biomedical Imaging, Department of Radiology, Columbus, OH (United States); Wuthrick, Evan J. [The Ohio State University Wexner Medical Center, Department of Radiation Oncology, Columbus, OH (United States)

    2017-07-15

    The purpose of this study was to evaluate the clinical feasibility of next generation solid-state digital photon counting PET/CT (dPET/CT) technology and imaging findings in patients following {sup 90}Y microsphere radioembolization in comparison with standard of care (SOC) bremsstrahlung SPECT/CT (bSPECT/CT). Five patients underwent SOC {sup 90}Y bremsstrahlung imaging immediately following routine radioembolization with 3.5 ± 1.7 GBq of {sup 90}Y-labeled glass microspheres. All patients also underwent dPET/CT imaging at 29 ± 11 h following radioembolization. Matched pairs comparison was used to compare image quality, image contrast and {sup 90}Y biodistribution between dPET/CT and bSPECT/CT images. Volumetric assessments of {sup 90}Y activity using different isocontour thresholds on dPET/CT and bSPECT/CT images were also compared. Digital PET/CT consistently provided better visual image quality and {sup 90}Y-to-background image contrast while depicting {sup 90}Y biodistribution than bSPECT/CT. Isocontour volumetric assessment using a 1% threshold precisely outlined {sup 90}Y activity and the treatment volume on dPET/CT images, whereas a more restrictive 20% threshold on bSPECT/CT images was needed to obtain comparable treatment volumes. The use of a less restrictive 10% threshold isocontour on bSPECT/CT images grossly overestimated the treatment volume when compared with the 1% threshold on dPET/CT images. Digital PET/CT is clinically feasible for the assessment of {sup 90}Y microsphere biodistribution following radioembolization, and provides better visual image quality and image contrast than routine bSPECT/CT with comparable acquisition times. With further optimization and clinical validation, dPET technology may allow faster and more accurate imaging-based assessment of {sup 90}Y microsphere biodistribution. (orig.)

  13. Early electrophysiological findings in Fisher-Bickerstaff syndrome.

    Science.gov (United States)

    Alberti, M A; Povedano, M; Montero, J; Casasnovas, C

    2017-09-06

    The term Fisher-Bickerstaff syndrome (FBS) has been proposed to describe the clinical spectrum encompassing Miller-Fisher syndrome (MFS) and Bickerstaff brainstem encephalitis. The pathophysiology of FBS and the nature of the underlying neuropathy (demyelinating or axonal) are still subject to debate. This study describes the main findings of an early neurophysiological study on 12 patients diagnosed with FBS. Retrospective evaluation of clinical characteristics and electrophysiological findings of 12 patients with FBS seen in our neurology department within 10 days of disease onset. Follow-up electrophysiological studies were also evaluated, where available. The most frequent electrophysiological finding, present in 5 (42%) patients, was reduced sensory nerve action potential (SNAP) amplitude in one or more nerves. Abnormalities were rarely found in motor neurography, with no signs of demyelination. The cranial nerve exam revealed abnormalities in 3 patients (facial neurography and/or blink reflex test). Three patients showed resolution of SNAP amplitude reduction in serial neurophysiological studies, suggesting the presence of reversible sensory nerve conduction block. Results from cranial MRI scans were normal in all patients. An electrophysiological pattern of sensory axonal neuropathy, with no associated signs of demyelination, is an early finding of FBS. Early neurophysiological evaluation and follow-up are essential for diagnosing patients with FBS. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. New surface radiolabeling schemes of super paramagnetic iron oxide nanoparticles (SPIONs) for biodistribution studies†

    Science.gov (United States)

    Nallathamby, Prakash D.; Mortensen, Ninell P.; Palko, Heather A.; Malfatti, Mike; Smith, Catherine; Sonnett, James; Doktycz, Mitchel J.; Gu, Baohua; Roeder, Ryan K.; Wang, Wei; Retterer, Scott T.

    2016-01-01

    Nanomaterial based drug delivery systems allow for the independent tuning of the surface chemical and physical properties that affect their biodistribution in vivo and the therapeutic payloads that they are intended to deliver. Additionally, the added therapeutic and diagnostic value of their inherent material properties often provides extra functionality. Iron based nanomaterials with their magnetic properties and easily tailorable surface chemistry are of particular interest as model systems. In this study the core radius of the iron oxide nanoparticles (NPs) was 14.08 ± 3.92 nm while the hydrodynamic radius of the NPs, as determined by Dynamic Light Scattering (DLS), was between 90–110 nm. In this study, different approaches were explored to create radiolabeled NPs that are stable in solution. The NPs were functionalized with polycarboxylate or polyamine surface functional groups. Polycarboxylate functionalized NPs had a zeta potential of –35 mV and polyamine functionalized NPs had a zeta potential of +40 mV. The polycarboxylate functionalized NPs were chosen for in vivo biodistribution studies and hence were radiolabeled with 14C, with a final activity of 0.097 nCi mg–1 of NPs. In chronic studies, the biodistribution profile is tracked using low-level radiolabeled proxies of the nanoparticles of interest. Conventionally, these radiolabeled proxies are chemically similar but not chemically identical to the non-radiolabeled NPs of interest. This study is novel as different approaches were explored to create radiolabeled NPs that are stable, possess a hydrodynamic radius of <100 nm and most importantly they exhibit an identical surface chemical functionality as their non-radiolabeled counterparts. Identical chemical functionality of the radiolabeled probes to the non-radiolabeled probes was an important consideration to generate statistically similar biodistribution data sets using multiple imaging and detection techniques. The radiolabeling approach

  15. Biodistribution of 99m technetium labeled creatinine in healthy rats

    International Nuclear Information System (INIS)

    Yilmaz, O.; Soylu, A.; Kavukcu, S.; Lambrecht, F. Yurt; Durkan, K.

    2007-01-01

    The distribution of creatinine, one of the toxic guanidine compounds, in various tissues has not been studied in detail by using radiolabeled creatinine. Our objective was to investigate the biodistribution of creatinine labeled with 99m technetium ( 99m Tc) by the stannous (II) chloride method in healthy male Wistar rats. Quality controls were carried out by radio thin layer chromatography, high-performance liquid chromatography, and paper electrophoresis. The labeling yield was 85 ± 2% under optimum conditions (pH 7 and 100 μg stannous chloride). Rats (N 12) were injected intravenously with 99m Tc creatinine and their blood and visceral organs were evaluated for 99m Tc-creatinine uptake as percent of the injected dose per gram wet weight of each tissue (%ID/g). The lowest amount of uptake was detected in the brain and testis. When the rate of uptake was evaluated, only the kidney showed increasing rates of uptake of 99m Tc-creatinine throughout the study. Kidneys showed the highest amount of uptake throughout the study (P < 0.001 compared to all other organs), followed by liver, spleen and lung tissue. (author)

  16. Biodistribution and Lymphatic Tracking of the Main Neurotoxin of Micrurus fulvius Venom by Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Irene Vergara

    2016-03-01

    Full Text Available The venom of the Eastern coral snake Micrurus fulvius can cause respiratory paralysis in the bitten patient, which is attributable to β-neurotoxins (β-NTx. The aim of this work was to study the biodistribution and lymphatic tracking by molecular imaging of the main β-NTx of M. fulvius venom. β-NTx was bioconjugated with the chelator diethylenetriaminepenta-acetic acid (DTPA and radiolabeled with the radionuclide Gallium-67. Radiolabeling efficiency was 60%–78%; radiochemical purity ≥92%; and stability at 48 h ≥ 85%. The median lethal dose (LD50 and PLA2 activity of bioconjugated β-NTx decreased 3 and 2.5 times, respectively, in comparison with native β-NTx. The immune recognition by polyclonal antibodies decreased 10 times. Biodistribution of β-NTx-DTPA-67Ga in rats showed increased uptake in popliteal, lumbar nodes and kidneys that was not observed with 67Ga-free. Accumulation in organs at 24 h was less than 1%, except for kidneys, where the average was 3.7%. The inoculation site works as a depot, since 10% of the initial dose of β-NTx-DTPA-67Ga remains there for up to 48 h. This work clearly demonstrates the lymphatic system participation in the biodistribution of β-NTx-DTPA-67Ga. Our approach could be applied to analyze the role of the lymphatic system in snakebite for a better understanding of envenoming.

  17. Brain-targeted solid lipid nanoparticles containing riluzole: preparation, characterization and biodistribution.

    Science.gov (United States)

    Bondì, Maria Luisa; Craparo, Emanuela Fabiola; Giammona, Gaetano; Drago, Filippo

    2010-01-01

    Developments within nanomedicine have revealed a great potential for drug delivery to the brain. In this study nanoparticulate systems as drug carriers for riluzole, with sufficiently high loading capacity and small particle size, were prepared to a reach therapeutic drug level in the brain. Solid lipid nanoparticles containing riluzole have great potential as drug-delivery systems for amyotrophic lateral sclerosis and were produced by using the warm oil-in-water microemulsion technique. The resulting systems obtained were approximately 88 nm in size and negatively charged. Drug-release profiles demonstrated that a drug release was dependent on medium pH. Biodistribution of riluzole blended into solid lipid nanoparticles was carried out after administration to rats and the results were compared with those obtained by riluzole aqueous dispersion administration. Rats were sacrificed at time intervals of 8, 16 and 30 h, and the riluzole concentration in the blood and organs such as the brain, liver, spleen, heart and kidney was determined. It was demonstrated that these solid lipid nanoparticles were able to successfully carry riluzole into the CNS. Moreover, a low drug biodistribution in organs such as the liver, spleen, heart, kidneys and lung was found when riluzole was administered as drug-loaded solid lipid nanoparticles. Riluzole-loaded solid lipid nanoparticles showed colloidal size and high drug loading, a greater efficacy than free riluzole in rats, a higher capability to carry the drug into the brain and a lower indiscriminate biodistribution.

  18. Investigations of a new, highly negative liposome with improved biodistribution for imaging

    International Nuclear Information System (INIS)

    Hnatowich, D.J.; Clancy, B.

    1980-01-01

    An attractive feature of liposomes is the wide range of lipid composition that can lead to liposome formation, coupled with the observation that liposome biodistribution may be altered by varying lipid composition. For instance, adding charged lipids to neutral lecithin will alter the biodistribution of the resulting charged liposomes. We have prepared highly negative liposomes by replacing lecithin with negatively charged cardiolipin. The liposomes have been labeled in the lipid phase with Ga-67 and Tc-99m oxine and their properties evaluated. The expected high negative charge of the resulting liposomes was confirmed by an ion-exchange chromatographic technique. Using paper chromatography, the stability of the label was determined during incubation in saline and serum. Finally, biodistributions were determined at 2 h in mice, and the results compared with those for negative lecithin liposomes. Accumulated activities in liver and spleen were reduced by factors of five and 20, respectively, over lecithin liposomes. Since preferential accumulation of activity in these organs constitutes the biggest limitation to the use of lecithin liposomes, cardiolipin liposomes may prove to be more useful carriers of radioactivity in imaging applications. More importantly, however, these results illustrate the value of studying novel liposome types as potential radiopharmaceuticals

  19. Biodistribution of the radiopharmaceutical technetium-99m-sodium phytate in rats after splenectomy

    International Nuclear Information System (INIS)

    Pereira, Kercia Regina Santos Gomes; Acucena, Maria Kadja Meneses Torres; Villarim Neto, Arthur; Rego, Amalia Cinthia Meneses; Bernardo-Filho, Mario; Azevedo, Italo Medeiros; Araujo Filho, Irami; Medeiros, Aldo Cunha

    2008-01-01

    Drugs and surgery can interfere with the biodistribution of radiopharmaceuticals and data about the effect of splenectomy on the metabolism of phytate-Tc-99m are scarce. This study aimed at evaluating the interference of splenectomy on phytate-Tc-99m biodistribution and liver function in rats. The SP group rats (n=6) underwent splenectomy. In group C (control) the animals were not operated on. After 15 days, all rats were injected with 0.1 mL of Tc-99m-phytate via orbital plexus (0.66 MBq). After 30 minutes, liver samples were harvested, weighed and the percentage of radioactivity per gram (%ATI/g) was determined by a Wizard Perkin-Elme gamma counter. The ATI%/g in splenectomized rats (0.99±0.02) was significantly higher than in controls (0.4±0.02), (p=0.034). ALT, AST and HDL were significantly lower in SP rats (p= 0.001) and leucocytosis was observed in SP rats. In conclusion, splenectomy in rats changed the hepatic biodistribution of Tc-99m-phytate and liver enzymatic activity. (author)

  20. Biodistribution of the radiopharmaceutical technetium-99m-sodium phytate in rats after splenectomy

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Kercia Regina Santos Gomes; Acucena, Maria Kadja Meneses Torres; Villarim Neto, Arthur; Rego, Amalia Cinthia Meneses [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Centro de Ciencias da Saude; Bernardo-Filho, Mario [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Dept. de Biofisica e Biometria; Azevedo, Italo Medeiros; Araujo Filho, Irami; Medeiros, Aldo Cunha [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Dept. de Cirurgia]. E-mail: aldo@ufrnet.br

    2008-12-15

    Drugs and surgery can interfere with the biodistribution of radiopharmaceuticals and data about the effect of splenectomy on the metabolism of phytate-Tc-99m are scarce. This study aimed at evaluating the interference of splenectomy on phytate-Tc-99m biodistribution and liver function in rats. The SP group rats (n=6) underwent splenectomy. In group C (control) the animals were not operated on. After 15 days, all rats were injected with 0.1 mL of Tc-99m-phytate via orbital plexus (0.66 MBq). After 30 minutes, liver samples were harvested, weighed and the percentage of radioactivity per gram (%ATI/g) was determined by a Wizard Perkin-Elme gamma counter. The ATI%/g in splenectomized rats (0.99{+-}0.02) was significantly higher than in controls (0.4{+-}0.02), (p=0.034). ALT, AST and HDL were significantly lower in SP rats (p= 0.001) and leucocytosis was observed in SP rats. In conclusion, splenectomy in rats changed the hepatic biodistribution of Tc-99m-phytate and liver enzymatic activity. (author)

  1. Effects of broccoli extract on biodistribution and labeling blood components with {sup 99m}Tc-GH

    Energy Technology Data Exchange (ETDEWEB)

    Cekic, Betul; Muftuler, Fazilet Zumrut Biber; Kilcar, Ayfer Yurt; Ichedef, Cigdem; Unak, Perihan [Ege University, Izmir (Turkey). Inst. of Nuclear Sciences. Dept. of Nuclear Applications

    2011-09-15

    Purpose: people consume vegetables without the knowledge of the side effects of the biological and chemical contents and interactions between radiopharmaceuticals and herbal extract. To this end, current study is focused on the effects of broccoli extract on biodistribution of radiolabeled glucoheptonate ({sup 99m}Tc-GH) and radiolabeling of blood components. Methods: GH was labeled with {sup 99m}Tc. Quality control studies were done utilizing TLC method. Biodistribution studies were performed on male rats which were treated via gavage with either broccoli extract or SF as control group for 15 days. Blood samples were withdrawn from rats' heart. Radiolabeling of blood constituents performed incubating with GH, SnCl{sub 2} and {sup 99m} Tc. Results: radiochemical yield of {sup 99m}Tc-GH is 98.46{+-}1.48 % (n=8). Biodistribution studies have shown that according to the control, the treated group with broccoli has approximately 10 times less uptake in kidney. The percentage of the radioactivity ratios of the blood components is found to be same in both groups. Conclusions: although there is no considerable effect on the radiolabeling of blood components, there is an outstanding change on the biodistribution studies especially on kidneys. The knowledge of this change on kidney uptake may contribute to reduce the risk of misdiagnosis and/or repetition of the examinations in Nuclear Medicine. (author)

  2. Tc 99m - scorpion venom: labelling, biodistribution and scintiimaging

    International Nuclear Information System (INIS)

    Murugesan, S.; Noronha, O.P.D.; Samuel, A.M.; Murthy, K. Radha Krishna

    1999-01-01

    Labelling of scorpion (Mesobuthus tamulus concanesis Pocock) venom was successfully achieved with Tc 99m using direct tin reduction procedure. Biodistribution studies were carried out in Wistar rats at different time intervals after i.v. administration of the labelled venom. Scintiimages were obtained after scorpion envenoming using a large field of view gamma camera to ascertain the pharmacological action of venom in the body. Within 5 min of administration, labelled venom was found in the blood (27.7%), muscle (30.11%), bone (13.3%), kidneys (11.5%), liver (10.4%) and other organs. The level of venom in the kidneys was higher than in the liver. The labelled venom was excreted through renal and hepatobiliary pathways. An immunoreactivity study was carried out in rabbits after i.v. injection of labelled scorpion venom followed by the injection of the species specific antivenom. A threefold increase in uptake by the kidneys ss was observed compared with that seen with scorpion venom alone. the neutralisation of the venom in the kidneys was higher than in the liver. (author)

  3. Toxicity and biodistribution of orally administered casein nanoparticles.

    Science.gov (United States)

    Gil, Ana Gloria; Irache, Juan Manuel; Peñuelas, Iván; González Navarro, Carlos Javier; López de Cerain, Adela

    2017-08-01

    In the last years, casein nanoparticles have been proposed as carriers for the oral delivery of biologically active compounds. However, till now, no information about their possible specific hazards in vivo was available. The aim of this work was to assess the safety of casein nanoparticles when administered orally to animals through a 90 days dose-repeated toxicity study (OECD guideline 408), that was performed in Wistar rats under GLP conditions. After 90 days, no evidences of significant alterations in animals treated daily with 50, 150 or 500 mg/kg bw of nanoparticles were found. This safety agrees well with the fact that nanoparticles were not absorbed and remained within the gut as observed by radiolabelling in the biodistribution study. After 28 days, there was a generalized hyperchloremia in males and females treated with the highest dose of 500 mg/kg bw, that was coupled with hypernatremia in the females. These effects were related to the presence of mannitol which was used as excipient in the formulation of casein nanoparticles. According to these results, the No Observed Adverse Effect Level (NOAEL) could be established in 150 mg/kg bw/day and the Lowest Observed Effect Level (LOEL) could be established in 500 mg/kg bw/day. Copyright © 2017. Published by Elsevier Ltd.

  4. In vivo biodistribution of stable spherical and filamentous micelles probed by high-sensitivity SPECT

    NARCIS (Netherlands)

    Jennings, L.; Ivashchenko, O.; Marsman, I. J C; Laan, A.C.; Denkova, A.G.; Waton, g; Beekman, F.J.; Schosseler, F.; Mendes, E.

    2016-01-01

    Understanding how nanoparticle properties such as size, morphology and rigidity influence their circulation time and biodistribution is essential for the development of nanomedicine therapies. Herein we assess the influence of morphology on cellular internalization, in vivo biodistribution and

  5. Biodistribution of the 18F-labelled advanced glycation end products Nε-carboxymethyllysine (CML) and Nε-carboxyethyllysine (CEL)

    International Nuclear Information System (INIS)

    Bergmann, R.; Helling, R.; Henle, T.; Heichert, C.; Scheunemann, M.; Maeding, P.; Wittrisch, H.; Johannsen, B.

    2002-01-01

    After synthesis of fluorine-18 labelled analogues [ 18 F]fluorobenzoylation at the α-amino group, biodistribution and elimination of individual advanced glycation end products, namely N ε -carboxymethyllysine and N ε -carboxyethyllysine, was studied in comparison to lysine in rats after intravenous injection using positron emission tomography. (orig.)

  6. The Use of Magnetic Resonance Imaging for Non-Invasive Assessment of Venofer® Biodistribution in Rats

    NARCIS (Netherlands)

    Span, Kimberley; Pieters, Ebel H.E.; Hennink, Wim E.; van der Toorn, Annette; Brinks, Vera; Dijkhuizen, Rick M.; van Tilborg, Geralda A.F.

    2018-01-01

    Purpose: The aim of this study was to determine the potential of magnetic resonance imaging to evaluate the biodistribution of exogenous iron within 24 h after one single injection of Venofer® (iron sucrose). Methods: Venofer® was evaluated in vitro for its ability to generate contrast in MR images.

  7. Automatic Parameterization Strategy for Cardiac Electrophysiology Simulations.

    Science.gov (United States)

    Costa, Caroline Mendonca; Hoetzl, Elena; Rocha, Bernardo Martins; Prassl, Anton J; Plank, Gernot

    2013-10-01

    Driven by recent advances in medical imaging, image segmentation and numerical techniques, computer models of ventricular electrophysiology account for increasingly finer levels of anatomical and biophysical detail. However, considering the large number of model parameters involved parameterization poses a major challenge. A minimum requirement in combined experimental and modeling studies is to achieve good agreement in activation and repolarization sequences between model and experiment or patient data. In this study, we propose basic techniques which aid in determining bidomain parameters to match activation sequences. An iterative parameterization algorithm is implemented which determines appropriate bulk conductivities which yield prescribed velocities. In addition, a method is proposed for splitting the computed bulk conductivities into individual bidomain conductivities by prescribing anisotropy ratios.

  8. A highly versatile and easily configurable system for plant electrophysiology.

    Science.gov (United States)

    Gunsé, Benet; Poschenrieder, Charlotte; Rankl, Simone; Schröeder, Peter; Rodrigo-Moreno, Ana; Barceló, Juan

    2016-01-01

    In this study we present a highly versatile and easily configurable system for measuring plant electrophysiological parameters and ionic flow rates, connected to a computer-controlled highly accurate positioning device. The modular software used allows easy customizable configurations for the measurement of electrophysiological parameters. Both the operational tests and the experiments already performed have been fully successful and rendered a low noise and highly stable signal. Assembly, programming and configuration examples are discussed. The system is a powerful technique that not only gives precise measuring of plant electrophysiological status, but also allows easy development of ad hoc configurations that are not constrained to plant studies. •We developed a highly modular system for electrophysiology measurements that can be used either in organs or cells and performs either steady or dynamic intra- and extracellular measurements that takes advantage of the easiness of visual object-oriented programming.•High precision accuracy in data acquisition under electrical noisy environments that allows it to run even in a laboratory close to electrical equipment that produce electrical noise.•The system makes an improvement of the currently used systems for monitoring and controlling high precision measurements and micromanipulation systems providing an open and customizable environment for multiple experimental needs.

  9. Biodistribution patterns of native and mutant 99mTc-labelled annexin V in mice

    International Nuclear Information System (INIS)

    Mariani, G.; Erba, P.; Pellegrino, D.; Volterrani, D.; Lazzeri, E.; Freer, G.; Bevilacqua, G.; Blankenberg, F.G.; Tait, J.F.; Strauss, H.W.

    2003-01-01

    Full text: Annexin is a 36 kD protein with high binding affinity to phosphatidylserine (PS), a phospholipid exposed on the membrane surface of cells upon activation of the enzyme caspase, the first step of apoptosis. Radiolabeled annexin V could thus be used for imaging apoptosis in-vivo. When the 319 amino acid protein is made by recombinant techniques and expressed as the human material, it can be radiolabeled with 99mTc after derivatization with a bifunctional agent such as HYNIC. Alternatively, the amino acid structure of the protein can be modified by producing annexin V mutants with an endogenous chelation site for 99mTc, the NH2 residue Ala-Gly-Gly-Cys-Gly-His-Met. Mutant annexin has similar affinity for membrane-bound PS as unmodified annexin. This study was performed to compare the biodistribution of 99mTc-labeled HYNIC annexin (HyA) to mutant annexin (MuA). 99mTc-labeling efficiency of the two annexin preparations was >99% by gel chromatography on Sephadex G10 columns. Groups of adult male mice (n 10, body weight 18-25 grams) were injected iv with either HyA or MuA (1-3 MBq, 3-9 μg/animal). Animals were sacrificed one hour later and dissected for organ biodistribution. Similar biodistribution was performed after pretreatment with cyclophosphamide (150 mg/kg ip 6-15 hr prior to the study). The results of the biodistribution study showed significantly reduced (p<0.05 to p<0.01) uptake of MuA versus HyA in the kidneys (Δ- 81.4%), spleen (Δ- 58.2%), liver (Δ- 56.2%), and bone marrow (Δ- 33.7%), while it was increased in lymph nodes (Δ+ 131%, p<0.001). Pretreatment with the pro-apoptotic agent cyclophosphamide induced significantly increased uptake of MuA (p<0.05) versus baseline in the heart (Δ+ 34.7%), spleen (Δ+ 30.1%) and bowel (Δ+ 44.5%), while uptake of HyA was increased only in the spleen (Δ+ 44.1%). The marked reduction in the renal, splenic, liver, and bone marrow localization of MuA compared to HyA in control animals outlines a pattern of

  10. Biofeedback in psychomotor training. Electrophysiological basis.

    Science.gov (United States)

    Bazanova, O M; Mernaya, E M; Shtark, M B

    2009-06-01

    The influences of individual musical practice and the same practice supplemented with biofeedback using electrophysiological markers for optimum music-performing activity were studied in 39 music students. Traditional technical practice produced increases in integral EMG power and decreases in alpha activity in most of the students with initially low maximum alpha activity peak frequencies. Similar practice but combined with individual sessions of alpha-EEG/EMG biofeedback were accompanied by increases in the frequency, bandwidth, and activation responses of EEG alpha rhythms in all subjects, along with decreases in EEG integral power. The efficacy of training with biofeedback and the ability to experience psychomotor learning depended on the initial individual characteristics of EEG alpha activity.

  11. Electrophysiological measurements of diabetic peripheral neuropathy: A systematic review.

    Science.gov (United States)

    Shabeeb, Dheyauldeen; Najafi, Masoud; Hasanzadeh, Gholamreza; Hadian, Mohammed Reza; Musa, Ahmed Eleojio; Shirazi, Alireza

    2018-03-28

    Peripheral neuropathy is one of the main complications of diabetes mellitus. One of the features of diabetic nerve damage is abnormality of sensory and motor nerve conduction study. An electrophysiological examination can be reproduced and is also a non-invasive approach in the assessment of peripheral nerve function. Population-based and clinical studies have been conducted to validate the sensitivity of these methods. When the diagnosis was based on clinical electrophysiological examination, abnormalities were observed in all patients. In this research, using a review design, we reviewed the issue of clinical electrophysiological examination of diabetic peripheral neuropathy in articles from 2008 to 2017. For this purpose, PubMed, Scopus and Embase databases of journals were used for searching articles. The researchers indicated that diabetes (both types) is a very disturbing health issue in the modern world and should be given serious attention. Based on conducted studies, it was demonstrated that there are different procedures for prevention and treatment of diabetes-related health problems such as diabetic polyneuropathy (DPN). The first objective quantitative indication of the peripheral neuropathy is abnormality of sensory and motor nerve conduction tests. Electrophysiology is accurate, reliable and sensitive. It can be reproduced and also is a noninvasive approach in the assessment of peripheral nerve function. The methodological review has found that the best method for quantitative indication of the peripheral neuropathy compared with all other methods is clinical electrophysiological examination. For best results, standard protocols such as temperature control and equipment calibration are recommended. Copyright © 2018. Published by Elsevier Ltd.

  12. Anatomical and Electrophysiological Clustering of Superficial Medial Entorhinal Cortex Interneurons

    Science.gov (United States)

    2017-01-01

    Abstract Local GABAergic interneurons regulate the activity of spatially-modulated principal cells in the medial entorhinal cortex (MEC), mediating stellate-to-stellate connectivity and possibly enabling grid formation via recurrent inhibitory circuitry. Despite the important role interneurons seem to play in the MEC cortical circuit, the combination of low cell counts and functional diversity has made systematic electrophysiological studies of these neurons difficult. For these reasons, there remains a paucity of knowledge on the electrophysiological profiles of superficial MEC interneuron populations. Taking advantage of glutamic acid decarboxylase 2 (GAD2)-IRES-tdTomato and PV-tdTomato transgenic mice, we targeted GABAergic interneurons for whole-cell patch-clamp recordings and characterized their passive membrane features, basic input/output properties and action potential (AP) shape. These electrophysiologically characterized cells were then anatomically reconstructed, with emphasis on axonal projections and pial depth. K-means clustering of interneuron anatomical and electrophysiological data optimally classified a population of 106 interneurons into four distinct clusters. The first cluster is comprised of layer 2- and 3-projecting, slow-firing interneurons. The second cluster is comprised largely of PV+ fast-firing interneurons that project mainly to layers 2 and 3. The third cluster contains layer 1- and 2-projecting interneurons, and the fourth cluster is made up of layer 1-projecting horizontal interneurons. These results, among others, will provide greater understanding of the electrophysiological characteristics of MEC interneurons, help guide future in vivo studies, and may aid in uncovering the mechanism of grid field formation. PMID:29085901

  13. Dosimetric estimation of O-(3-18F-fluoropropyl)-L-tyrosine in human based on mice biodistribution data

    International Nuclear Information System (INIS)

    Tang Ganghua; Wang Mingfang; Luo Lei; Gan Manquan; Tang Xiaolan

    2002-01-01

    Objective: To estimate the radiation absorbed doses in humans due to intravenous administration of O-(3- 18 F-fluoropropyl)-L-tyrosine (FPT) based on mice biodistribution data and appraise the security of FPT in humans. Methods: FPT was injected into mice through a tail vein. At 10, 30, 60, 120 and 180 min after injection, the mice were killed by cervical fracture and biodistribution in mice were determined. Human dosimetric estimation was performed from the biodistribution of FPT in mice and the standard MIRD method using fractional radioactivity-time curves for humans. Results: The bone in human was the organ receiving highest dose of 4.29 x 10 -3 mGy/MBq, the brain received lowest dose of 1.57 x 10 -3 mGy/MBq, and other organs received doses between 1.8 x 10 -3 and 2.4 x 10 -3 mGy/MBq. The effective dose was estimated to be 9.15 x 10 -3 mSv/MBq. These results were comparable to values reported by foreign authors on the radiation dosimetry of O-(2- 18 F-fluoroethyl)-L-tyrosine. Conclusion: Human dosimetric estimation can be performed based on mice biodistribution data. The study provides an important data for clinical safety of FPT

  14. Prognosis assessment of persistent left bundle branch block after TAVI by an electrophysiological and remote monitoring risk-adapted algorithm: rationale and design of the multicentre LBBB-TAVI Study.

    Science.gov (United States)

    Massoullié, Grégoire; Bordachar, Pierre; Irles, Didier; Caussin, Christophe; Da Costa, Antoine; Defaye, Pascal; Jean, Frédéric; Mechulan, Alexis; Mondoly, Pierre; Souteyrand, Géraud; Pereira, Bruno; Ploux, Sylvain; Eschalier, Romain

    2016-10-26

    Percutaneous aortic valve replacement (transcatheter aortic valve implantation (TAVI)) notably increases the likelihood of the appearance of a complete left bundle branch block (LBBB) by direct lesion of the LBB of His. This block can lead to high-grade atrioventricular conduction disturbances responsible for a poorer prognosis. The management of this complication remains controversial. The screening of LBBB after TAVI persisting for more than 24 hours will be conducted by surface ECG. Stratification will be performed by post-TAVI intracardiac electrophysiological study. Patients at high risk of conduction disturbances (≥70 ms His-ventricle interval (HV) or presence of infra-Hisian block) will be implanted with a pacemaker enabling the recording of disturbance episodes. Those at lower risk (HV algorithm based on electrophysiological study and remote monitoring of CIEDs in the prediction of high-grade conduction disturbances in patients with LBBB after TAVI. The primary end point is to compare the incidence (rate and time to onset) of high-grade conduction disturbances in patients with LBBB after TAVI between the two groups at 12 months. Given the proportion of high-grade conduction disturbances (20-40%), a sample of 200 subjects will allow a margin of error of 6-7%. The LBBB-TAVI Study has been in an active recruiting phase since September 2015 (21 patients already included). Local ethics committee authorisation was obtained in May 2015. We will publish findings from this study in a peer-reviewed scientific journal and present results at national and international conferences. NCT02482844; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. Effect of alectinib on cardiac electrophysiology: results from intensive electrocardiogram monitoring from the pivotal phase II NP28761 and NP28673 studies.

    Science.gov (United States)

    Morcos, Peter N; Bogman, Katrijn; Hubeaux, Stanislas; Sturm-Pellanda, Carolina; Ruf, Thorsten; Bordogna, Walter; Golding, Sophie; Zeaiter, Ali; Abt, Markus; Balas, Bogdana

    2017-03-01

    Alectinib, a central nervous system (CNS)-active ALK inhibitor, has demonstrated efficacy and safety in ALK+ non-small-cell lung cancer that has progressed following crizotinib treatment. Other ALK inhibitors have shown concentration-dependent QTc prolongation and treatment-related bradycardia. Therefore, this analysis evaluated alectinib safety in terms of electrophysiologic parameters. Intensive triplicate centrally read electrocardiogram (ECG) and matched pharmacokinetic data were collected across two alectinib single-arm trials. Analysis of QTcF included central tendency analysis [mean changes from baseline with one-sided upper 95% confidence intervals (CIs)], categorical analyses, and relationship between change in QTcF and alectinib plasma concentrations. Alectinib effects on other ECG parameters (heart rate, PR interval and QRS duration) were also evaluated. Alectinib did not cause a clinically relevant change in QTcF. The maximum mean QTcF change from baseline was 5.3 ms observed pre-dose at week 2. The upper one-sided 95% CI was exposure-dependent decrease in mean heart rate of ~11 to 13 beats per minute at week 2. No clinically relevant effects were seen on other ECG parameters. Approximately 5% of patients reported cardiac adverse events of bradycardia or sinus bradycardia; however, these were all grade 1-2. Alectinib does not prolong the QTc interval or cause changes in cardiac function to a clinically relevant extent, with the exception of a decrease in heart rate which was generally asymptomatic.

  16. Influence of sweeteners in the biodistribution of radiopharmaceutical ...

    African Journals Online (AJOL)

    Influence of sweeteners in the biodistribution of radiopharmaceutical and laboratory tests in rats. Michelly Pires Queiroz, Vanessa Santos de Arruda Barbosa, Cecília Maria de Carvalho Xavier Holanda, Janette Monroy Osório, Tarciso Bruno Montenegro Sampaio, Christina da Silva Camillo, Aldo Cunha Medeiros, Marília ...

  17. Pelvic floor electrophysiology patterns associated with faecal ...

    African Journals Online (AJOL)

    Hussein Al-Moghazy Sultan

    2012-12-28

    Dec 28, 2012 ... pelvic floor electrophysiological abnormalities associated with. FI were illustrated in ... detection of a localized anal sphincter defect clinically and ..... Woods R, Voyvodic F, Schloithe A, Sage M, Wattchow D. Anal sphincter ...

  18. Effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1

    International Nuclear Information System (INIS)

    Watanabe, Ayahisa; Nishijima, Ken-ichi; Zhao, Songji; Tamaki, Nagara; Kuge, Yuji; Tanaka, Yoshikazu; Itoh, Takeshi; Takemoto, Hiroshi

    2012-01-01

    Glycosylation is generally applicable as a strategy for increasing the activity of bioactive proteins. In this study, we examined the effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1 (GLP-1) as a bioactive peptide for type 2 diabetes. Noninvasive imaging studies were performed using a gamma camera after the intravenous administration of 123 I-GLP-1 or 123 I-α2, 6-sialyl N-acetyllactosamine (glycosylated) GLP-1 in rats. In ex vivo biodistribution studies using 125 I-GLP-1 or 125 I-glycosylated GLP-1, organ samples were measured for radioactivity. Plasma samples were added to 15% trichloroacetic acid (TCA) to obtain TCA-insoluble and TCA-soluble fractions. The radioactivity in the TCA-insoluble and TCA-soluble fractions was measured. In the noninvasive imaging studies, a relatively high accumulation level of 123 I-GLP-1 was found in the liver, which is the major organ to eliminate exogenous GLP-1. The area under the time-activity curve (AUC) of 123 I-glycosylated GLP-1 in the liver was significantly lower (89%) than that of 123 I-GLP-1. These results were consistent with those of ex vivo biodistribution studies using 125 I-labeled peptides. The AUC of 125 I-glycosylated GLP-1 in the TCA-insoluble fraction was significantly higher (1.7-fold) than that of GLP-1. This study demonstrated that glycosylation significantly decreased the distribution of radiolabeled GLP-1 into the liver and increased the concentration of radiolabeled GLP-1 in plasma. These results suggested that glycosylation is a useful strategy for decreasing the distribution into the liver of bioactive peptides as desirable pharmaceuticals. (author)

  19. Biodistribution of radiolabelled human dendritic cells injected by various routes

    International Nuclear Information System (INIS)

    Quillien, Veronique; Moisan, Annick; Carsin, Andre; Lesimple, Thierry; Lefeuvre, Claudia; Bertho, Nicolas; Devillers, Anne; Toujas, Louis; Adamski, Henri; Leberre, Claudine

    2005-01-01

    The purpose of this study was to investigate the biodistribution of mature dendritic cells (DCs) injected by various routes, during a cell therapy protocol. In the context of a vaccine therapy protocol for melanoma, DCs matured with Ribomunyl and interferon-gamma were labelled with 111 In-oxine and injected into eight patients along various routes: afferent lymphatic vessel (IL) (4 times), lymph node (IN) (5 times) and intradermally (ID) (6 times). Scintigraphic investigations showed that the IL route allowed localisation of 80% of injected radioactivity in eight to ten nodes. In three cases of IN injection, the entire radioactivity stagnated in the injected nodes, while in two cases, migration to adjacent nodes was observed. This migration was detected rapidly after injection, as with IL injections, suggesting that passive transport occurred along the physiological lymphatic pathways. In two of the six ID injections, 1-2% of injected radioactivity reached a proximal lymph node. Migration was detectable in the first hour, but increased considerably after 24 h, suggesting an active migration mechanism. In both of the aforementioned cases, DCs were strongly CCR7-positive, but this feature was not a sufficient condition for effective migration. In comparison with DCs matured with TNF-α, IL-1β, IL-6 and PGE2, our DCs showed a weaker in vitro migratory response to CCL21, despite comparable CCR7 expression, and higher allostimulatory and TH1 polarisation capacities. The IL route allowed reproducible administration of specified numbers of DCs. The IN route sometimes yielded fairly similar results, but not reproducibly. Lastly, we showed that DCs matured without PGE2 that have in vitro TH1 polarisation capacities can migrate to lymph nodes after ID injection. (orig.)

  20. Biological Effects and Biodistribution of Bufotenine on Mice

    Directory of Open Access Journals (Sweden)

    Hugo Vigerelli

    2018-01-01

    Full Text Available Bufotenine is an alkaloid derived from serotonin, structurally similar to LSD and psilocin. This molecule is able to inhibit the rabies virus infection in in vitro and in vivo models, increasing the survival rate of infected animals. Being a very promising molecule for an incurable disease and because of the fact that there is no consensus regarding its neurological effects, this study aimed to evaluate chronic treatment of bufotenine on behavior, pathophysiology, and pharmacokinetics of mice. Animals were daily treated for 21 consecutive days with 0.63, 1.05, and 2.1 mg/animal/day bufotenine and evaluated by open field test and physiological parameters during all the experiment. After this period, organs were collected for histopathological and biodistribution analysis. Animals treated with bufotenine had mild behavioral alterations compared to the control group, being dose-response relationship. On the other hand, animals showed normal physiological functions and no histological alterations in the organs. With high doses, an inflammatory reaction was observed in the site of injection, but with no cellular damage. The alkaloid could be found in the heart and kidney with all doses and in the lungs and brain with higher doses. These results show that the effective dose, 0.63 mg/day, is safe to be administered in mice, since it did not cause significant effects on the animals’ physiology and on the CNS. Higher doses were well tolerated, causing only mild behavioral effects. Thus, bufotenine might be a drug prototype for rabies treatment, an incurable disease.

  1. Altered biodistribution of FDG in patients with type-2 diabetes mellitus

    International Nuclear Information System (INIS)

    Ozguven, M.A.; Karacalioglu, A.O.; Ince, S.; Emer, M.O.

    2014-01-01

    Positron emission tomography-computed tomography (PET-CT) imaging of patients with diabetes can be problematic because elevated glucose levels may cause competitive inhibition of [F-18]-2-deoxy-2-fluoro-D-glucose (FDG) uptake in different tissues. Therefore, the aim of the study was to evaluate the biodistribution of FDG in patients with type-2 diabetes mellitus. Two hundred forty patients were retrospectively enrolled to the study. Study population was divided into three subgroups, named as the normal (group 1), the insulin (group 2) and the oral anti-diabetic (group 3). Unenhanced low-dose CT and PET emission data were acquired from the mid-thigh to the vertex of the skull. FDG uptakes in different organs were evaluated qualitatively or semi-quantitatively. In the diabetic groups, diffuse FDG uptake of the colon was increased (p > 0.001) but segmental FDG uptake was decreased (p > 0.001). Intestinal FDG uptake was detected in 20% of the study population and only 3% of these uptakes were in diffuse pattern. Segmental FDG uptake in the bowel was increased significantly in the groups of patients with diabetes (p = 0.002). Maximum standardized uptake values of the liver in the groups 1, 2, and 3 were 2.66 ± 0.6, 3.25 ± 0.9 and 3.16 ± 0.8, respectively, and the difference between the groups was not statistically significant (p = 0.083). Cardiac FDG uptake was decreased significantly in the groups of patients with diabetes (p < 0.001). According to our results, whole body bio-distribution of FDG uptake seems to be changed in patients with type-2 diabetes who were using insulin or oral anti-diabetic drugs. Although the use of oral antidiabetic drugs was known to change the biodistribution of FDG, insulin use also seems to change FDG uptake in different organs of diabetic patients. (author)

  2. Effects of MRI on the electrophysiology of the motor cortex: a TMS study; Auswirkungen der Magnetresonanztomografie auf die Elektrophysiologie des motorischen Kortex: eine Studie mit transkranieller Magnetstimulation

    Energy Technology Data Exchange (ETDEWEB)

    Schlamann, Marc; Pietrzyk, T. [Universitaetsklinikum Essen (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie; Yoon, M.S.; Gerwig, M.; Kastrup, O. [Universitaetsklinikum Essen (Germany). Neurologische Klinik; Maderwald, S.; Forsting, M.; Ladd, S.C. [Universitaetsklinikum Essen (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie; Duisburg-Essen Univ. (Germany). Erwin-L.-Hahn-Inst. fuer Magnetresonanz; Bitz, A.; Ladd, M.E. [Duisburg-Essen Univ. (Germany). Erwin-L.-Hahn-Inst. fuer Magnetresonanz

    2009-03-15

    The increasing spread of high-field and ultra-high-field MRI scanners encouraged a new discussion on safety aspects of MRI examinations. Earlier studies report altered acoustically evoked potentials. This finding was not able to be confirmed in later studies. In the present study transcranial magnetic stimulation (TMS) was used to evaluate whether motor cortical excitability may be altered following MRI examination even at field strength of 1.5 T. In 12 right-handed male volunteers individual thresholds for motor responses and then the length of the post-excitatory inhibition (silent period) were determined. Subsequently the volunteers were examined in the MRI scanner (Siemens Avanto, 1.5 T) for 63 minutes using gradient and spin echo sequences. MRI examination was immediately followed by another TMS session and a third 10 minutes later. As a control condition, the 12 subjects spent one hour in the scanner without examination and one hour on a couch without the presence of a scanner. After MRI examination, the silent period was significantly lengthened in all 12 subjects and then tended to the initial value after 10 min. Motor thresholds were significantly elevated and then normalized after 10 minutes. No significant effects were found in the control conditions. (orig.)

  3. 188Re labeling and biodistribution of magnetic nanoparticles for the tumor targeting

    International Nuclear Information System (INIS)

    Li Guiping; Zhang Hui; Wang Yongxian; Zhang Chunfu

    2006-01-01

    Objective: To prepare 188 Re labeled monoclonal antibody (Herceptin)-coated magnetic nanoparticles for tumor targeting and to study its biodistribution in mice. Methods: Herceptin and histidine were covalently linked to the amine group upon silica-coated magnetic nanoparticles modified by N-[3-(trimethyoxysilyl)prowl]-ethylenediamine using glutaraldehyde method. The Herceptin-coated magnetic nanoparticles and Herceptin were radiolabeled with 188 Re by a direct labelling method, whereas the histidine-coated magnetic nanoparticles was radiolabeled with 188 Re using fac-[ 188 Re(CO) 3 (H 2 0) 3 ] + as a precursor. The labelling efficiency and immunoreactivity as well as labelling stability were determined. Also, the biodistribution of 188 Re-magnetic and 188 Re-Herceptin-magnetic nanoparticles were observed in mice. Results: Herceptin-coated magnetic nanoparticles was characterized by transmission electron microscope (TEM) with diameter about 60 nm, while histidine-coated magnetic nanoparticles about 30 nm. The labeling efficiency for 188 Re-Herceptin, 188 Re-magnetic nanoparticles and 188 Re-Herceptin-magnetic nanoparticles were all > 90% and had a better stability in vitro. The immunoreactivity of Herceptin linked to magnetic nanoparticles was still high. The biodistribution in mice was shown that 188 Re-magnetic nanoparticles and 188 Re-Herceptin- magnetic nanoparticles had higher radioactivity levels in blood. Magnetic nanoparticles with diameter of 30 or 60 nm had a long half-life in blood stream and were accumulated in liver. Conclusion: The efficiency and stability of labelling Herceptin-coated magnetic nanoparticles and labelling magnetic nanoparticles with 188 Re are suitable for in vivo study in tumor-beating nude mice models. (authors)

  4. Dimercaptosuccinic acid-Tc99m: Preparation and biodistribution in rats

    International Nuclear Information System (INIS)

    Smal, F.; Englebienne, P.

    1976-01-01

    Owing to the juxtaposition of 4 ligands (2 SH groups + 2 COOH groups), dimercaptosuccinic acid has a strong chelating capacity which suits it for technetium 99 m labelling. The study is carried out in 2 stages: preparation and stability of the dimercaptosuccinic acid - stannous chloride complex (DMSA-Sn); biodistribution of DMSA-Sn-Tc99m complex in rats as a function of the following parameters: pH, relative stannous chloride and dimercaptosuccinic acid concentrations, TcO 4 volume added, injection time after labelling. The strong activity uptake obtained in rat kidneys represents a considerable step forward in the radioisotopic kidney examination and offers the prospect of clinical use [fr

  5. Biodistribution of doxorubicin and nanostructured ferrocarbon carrier particles in organism during magnetically controlled drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Kuznetsov, Anatoly A.; Filippov, Victor I.; Nikolskaya, Tatiana A. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation); Budko, Andrei P. [Oncological Center, Russian Academy of Medical Sciences, Moscow (Russian Federation); Kovarskii, Alexander L. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation); Zontov, Sergei V. [Oncological Center, Russian Academy of Medical Sciences, Moscow (Russian Federation); Kogan, Boris Ya. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation); Kuznetsov, Oleg A. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation)], E-mail: kuznetsov_oa@yahoo.com

    2009-05-15

    Biodistribution of doxorubicin and ferrocarbon carrier particles in organism during and after magnetically controlled anti-tumor drug delivery and deposition was studied. Animal tests show high concentration of the cytostatic drug in the target zone, while its concentration is three orders of magnitude lower in bloodstream and other organs. A significant depot of the drug remains on the deposited particles days after the procedure. Macrophages actively phagocytose the ferrocarbon (FeC) particles and remain viable long enough to carry them to the lymph nodes.

  6. Biodistribution of doxorubicin and nanostructured ferrocarbon carrier particles in organism during magnetically controlled drug delivery

    International Nuclear Information System (INIS)

    Kuznetsov, Anatoly A.; Filippov, Victor I.; Nikolskaya, Tatiana A.; Budko, Andrei P.; Kovarskii, Alexander L.; Zontov, Sergei V.; Kogan, Boris Ya.; Kuznetsov, Oleg A.

    2009-01-01

    Biodistribution of doxorubicin and ferrocarbon carrier particles in organism during and after magnetically controlled anti-tumor drug delivery and deposition was studied. Animal tests show high concentration of the cytostatic drug in the target zone, while its concentration is three orders of magnitude lower in bloodstream and other organs. A significant depot of the drug remains on the deposited particles days after the procedure. Macrophages actively phagocytose the ferrocarbon (FeC) particles and remain viable long enough to carry them to the lymph nodes.

  7. Modeling of biodistribution of 90 Y-DOTA-hR3 by using artificial intelligence techniques

    International Nuclear Information System (INIS)

    Ondarse, Dianelys; Quiza, Ramon; Leyva, Rene; Zamora, Minely; Ducat, Luis; Hernandez, Ignacio; Alonso, Luis Michel

    2011-01-01

    In this work the biodistribution of radioimmunoconjugate 9 0Y-DOTA-hR3 was modeled by using an artificial neural network. In vivo stability of 9 0Y-DOTA-hR3 was determined in healthy male Wistar rats at 4, 24 and 48 hours, in different organs. A model describing the relationship between, by one hand, the incorporated dose and, by the other hand, organ and time was developed by using a multilayer perceptron neural network. Adjusted model was analyzed by several statistical tests. Outcomes shown that proposed neural model describes the relationship between the studied variables in a proper way. (Author)

  8. Synthesis, radioiodination, and biodistribution of some nido- and closo-monocarbon carborane derivatives

    International Nuclear Information System (INIS)

    Wilbur, D. Scott; Hamlin, Donald K.; Srivastava, Rajiv R.; Chyan, Ming-Kuan

    2004-01-01

    Iodination and radioiodination reactions of several anionic nido- and closo-monocarbon carboranes were conducted. Iodinations occurred more rapidly with nido-carboranes than with closo-carboranes. The most rapid iodination and radioiodination reactions occurred with unsubstituted carboranes. C-amino and C-ammonium derivatives did not iodinate under the conditions studied. Both nido- and closo-carboranes with C-NH-acetyl and C-NH-succinyl substituents iodinated, but the nido-carboranes iodinated under milder reaction conditions. Biodistributions of nido-1-succinylamido-[ 131 I]carborane and closo-1-succinylamido-[ 125 I]carborane were similar in mice, but blood clearance of the nido- compound was slower

  9. Predicting the biodistribution of radiolabeled cMORF effector in MORF-pretargeted mice

    International Nuclear Information System (INIS)

    Liu, Guozheng; Dou, Shuping; He, Jiang; Liu, Xinrong; Rusckowski, Mary; Hnatowich, Donald J.

    2007-01-01

    Pretargeting with phosphorodiamidate morpholino oligomers (MORFs) involves administration of a MORF-conjugated anti-tumor antibody such as MN14 as a pretargeting agent before that of the radiolabeled complementary MORF (cMORF) as the effector. The dosages of the pretargeting agent and effector, the pretargeting interval, and the detection time are the four pretargeting variables. The goal of this study was to develop a semiempirical description capable of predicting the biodistribution of the radiolabeled effector in pretargeted mice and then to compare predictions with experimental results from pretargeting studies in tumored animals in which the pretargeting interval and the detection time were both fixed but the dosages of both the effector and the pretargeting agent were separately varied. Pretargeting studies in LS174T tumored mice were performed using the anti-CEA antibody MN14 conjugated with MORF and the cMORF radiolabeled with 99m Tc. A description was developed based on our previous observations in the same mouse model of the blood and tumor levels of MORF-MN14, accessibility of MORF-MN14 to labeled cMORF, the tumor accumulation of labeled cMORF relative to MORF-MN14 levels therein, and the kidney accumulation of labeled cMORF. The predicted values were then compared with the experimental values. The predicted biodistribution of the radiolabeled effector and the experimental data were in gratifying agreement in normal organs, suggesting that the description of the pretargeting process was reliable. The tumor accumulations occasionally fell outside two standard deviations of that predicted, but after tumor size correction, good agreement between predicted and experimental values was observed here as well. A semiempirical description of the biodistribution of labeled cMORF was capable of predicting the biodistribution of the radiolabeled effector in the pretargeted tumored mouse model, demonstrating that the underlying pretargeting concepts are correct. We

  10. Synthesis, quality control and biodistribution of 99mTc-Kanamycin

    International Nuclear Information System (INIS)

    Roohi, S.; Mushtaq, A.; Jehangir, M.; Malik, S.A.

    2006-01-01

    Kanamycin is an antibiotic used for treatment of infections when penicillin or other less toxic drugs cannot be used. Kanamycin was labeled with technetium-99m pertechnetate using SnCl 2 x 2H 2 O as reducing agent. The labeling efficiency depends on the ligand/reductant ratio, pH, and volume of reaction mixture. Radiochemical purity and stability of 99m Tc-Kanamycin was determined by thin layer chromatography. Biodistribution studies of 99m Tc-Kanamycin were performed in rats and rabbits. A significantly higher accumulation of 99m Tc-Kanamycin was seen at sites of S. aureus infected animals (rat/rabbit). (author)

  11. Whole-body biodistribution, dosimetry and metabolite correction of [11C]palmitate: A PET tracer for imaging of fatty acid metabolism

    DEFF Research Database (Denmark)

    Christensen, Nana Louise; Jakobsen, Steen; Schacht, Anna Christina

    2017-01-01

    INTRODUCTION: Despite the decades long use of [11C]palmitate positron emission tomography (PET)/computed tomography in basic metabolism studies, only personal communications regarding dosimetry and biodistribution data have been published. METHODS: Dosimetry and biodistribution studies were...... performed in 2 pigs and 2 healthy volunteers by whole-body [11C]palmitate PET scans. Metabolite studies were performed in 40 participants (healthy and with type 2 diabetes) under basal and hyperinsulinemic conditions. Metabolites were estimated using 2 approaches and subsequently compared: Indirect [11C]CO2...

  12. Labeling method of 17-allylamino, 17-demethoxygeldanamycin with 131I and its biodistribution in experimental animals

    International Nuclear Information System (INIS)

    Jiang Xinyu; Liu Lu; Gao Wen; Chen Daozhen; Huang Ying; Yang Min; Luo Shineng

    2008-01-01

    Objective: The aims of the study were to find out the optimal 131 I labeling method with 17-allylamino, 17-demethoxygeldanamycin (17-AAG) and also to study its biodistribution in animals. Methods: 131 I-17-AAG was prepared by the reaction of 17-AAG with Na 131 I in the presence of hydrogen peroxide. The labeling efficiency and the stability of 131 I-17-AAG were measured by paper chromatograph. The biodistribution in the ICR normal mice was observed by the blood samplings and major organs that were taken out from mice at 0.5, 1, 4, 8, 24 h after 131 I-17-AAG injection through tail veins. VX2 tumor was also implanted in rabbit liver for in vivo imaging with SPECT. Results: The optimal labeling conditions of 17-AAG with mi were determined. The labeling efficiency was 85.65%. The radiochemical purity of 131 I- 17-AAG in acetoacetate solution was (96.51 ± 0.80)% after purification and its radiochemical purity in normal saline solution was (95.57 ± 0.09)%. The radiochemical purity could keep to 90% in normal saline after 5 d at 4 degree C. The biodistribution study in normal mice showed that the uptake (percentage activity of injection dose per gram of tissue, % ID/g) in liver and kidney was less than that in cholecyst [(3.0963 ± 1.3394) %ID/g] at 0.5 h post-injection, and the uptake in stomach and intestine reached to the highest level at 4 h post-injection. The SPECT images showed that the 131 I-17-AAG was obviously concentrated in the tumor after injection at 2 h and 4 d, 6 d, 14 d with the highest tumor to non-tumor (T/NT) radioactivity ratio of 10.36. Conclusions: The labeling method of 17-AAG with 131 I was successfully established. The 131 I-17-AAG in normal saline had a good stability. The main biodistribution in mice was in digestive system and was excreted through the intestinal tract. The SPECT images showed that 131 I-17-AAG might be a potential target-directed agent to the tumor. (authors)

  13. Subthalamic stimulation: toward a simplification of the electrophysiological procedure.

    Science.gov (United States)

    Fetter, Damien; Derrey, Stephane; Lefaucheur, Romain; Borden, Alaina; Wallon, David; Chastan, Nathalie; Maltete, David

    2016-06-01

    The aim of the present study was to assess the consequences of a simplification of the electrophysiological procedure on the post-operative clinical outcome after subthalamic nucleus implantation in Parkinson disease. Microelectrode recordings were performed on 5 parallel trajectories in group 1 and less than 5 trajectories in group 2. Clinical evaluations were performed 1 month before and 6 months after surgery. After surgery, the UPDRS III score in the off-drug/on-stimulation and on-drug/on-stimulation conditions significantly improved by 66,9% and 82%, respectively in group 1, and by 65.8% and 82.3% in group 2 (P<0.05). Meanwhile, the total number of words (P<0.05) significantly decreased for fluency tasks in both groups. Motor disability improvement and medication reduction were similar in both groups. Our results suggest that the electrophysiological procedure should be simplified as the team's experience increases.

  14. Dual-modality NIRF-MRI cubosomes and hexosomes: High throughput formulation and in vivo biodistribution

    Energy Technology Data Exchange (ETDEWEB)

    Tran, Nhiem, E-mail: nhiem.tran@rmit.edu.au [CSIRO Manufacturing, Clayton, Victoria 3168 (Australia); Australian Synchrotron, Clayton, Victoria 3168 (Australia); RMIT University, Melbourne, Victoria 3000 (Australia); Bye, Nicole; Moffat, Bradford A. [Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, Victoria 3010 (Australia); Wright, David K. [Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, Victoria 3010 (Australia); The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria 3052 (Australia); Cuddihy, Andrew [Myeloma Research Group, Australian Centre for Blood Diseases, Monash Central Clinical School, The Alfred Hospital, Melbourne, Victoria 3004 (Australia); Hinton, Tracey M. [CSIRO Australian Animal Health Laboratory, East Geelong, Victoria 3219 (Australia); Hawley, Adrian M. [Australian Synchrotron, Clayton, Victoria 3168 (Australia); Reynolds, Nicholas P. [CSIRO Manufacturing, Clayton, Victoria 3168 (Australia); ARC Training Centre for Biodevices, Faculty of Science Engineering and Technology, Swinburne University of Technology, Melbourne, Victoria 3122 (Australia); Waddington, Lynne J.; Mulet, Xavier [CSIRO Manufacturing, Clayton, Victoria 3168 (Australia); Turnley, Ann M. [Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, Victoria 3010 (Australia); Morganti-Kossmann, M. Cristina [Australian New Zealand Intensive Care Research Centre, Monash University, Victoria 3800 (Australia); Department of Child Health, Barrow Neurological Institute, University of Arizona, Phoenix, AZ 85004 (United States); Muir, Benjamin W., E-mail: ben.muir@csiro.au [CSIRO Manufacturing, Clayton, Victoria 3168 (Australia)

    2017-02-01

    Engineered nanoparticles with multiple complementary imaging modalities are of great benefit to the rapid treatment and diagnosis of disease in various organs. Herein, we report the formulation of cubosomes and hexosomes that carry multiple amphiphilic imaging contrast agents in their self-assembled lipid bilayers. This is the first report of the use of both near infrared fluorescent (NIRF) imaging and gadolinium lipid based magnetic resonance (MR) imaging modalities in cubosomes and hexosomes. High-throughput screening was used to rapidly optimize formulations with desirable nano-architectures and low in vitro cytotoxicity. The dual-modal imaging nanoparticles in vivo biodistribution and organ specific contrast enhancement were then studied. The NIRF in vivo imaging results indicated accumulation of both cubosomes and hexosomes in the liver and spleen of mice up to 20 h post-injection. Remarkably, the biodistribution of the nanoparticle formulations was affected by the mesophase (i.e. cubic or hexagonal), a finding of significant importance for the future use of these compounds, with hexosomes showing higher accumulation in the spleen than the liver compared to cubosomes. Furthermore, in vivo MRI data of animals injected with either type of lyotropic liquid crystal nanoparticle displayed enhanced contrast in the liver and spleen. - Highlights: • Dual modality NIRF-MR imaging self-assembled lipid nanoparticles were formulated. • The nanoparticles showed cubic and hexagonal internal nanostructures. • Biodistribution experiments revealed accumulation of both cubosomes and hexosomes in spleen and liver of mice. • Pre-clinical MRI displayed enhanced contrast in spleen and liver of mice that received either cubosomes or hexosomes.

  15. Docetaxel-loaded PLGA and PLGA-PEG nanoparticles for intravenous application: pharmacokinetics and biodistribution profile.

    Science.gov (United States)

    Rafiei, Pedram; Haddadi, Azita

    2017-01-01

    Docetaxel is a highly potent anticancer agent being used in a wide spectrum of cancer types. There are important matters of concern regarding the drug's pharmacokinetics related to the conventional formulation. Poly(lactide- co -glycolide) (PLGA) is a biocompatible/biodegradable polymer with variable physicochemical characteristics, and its application in human has been approved by the United States Food and Drug Administration. PLGA gives polymeric nanoparticles with unique drug delivery characteristics. The application of PLGA nanoparticles (NPs) as intravenous (IV) sustained-release delivery vehicles for docetaxel can favorably modify pharmacokinetics, biofate, and pharmacotherapy of the drug in cancer patients. Surface modification of PLGA NPs with poly(ethylene glycol) (PEG) can further enhance NPs' long-circulating properties. Herein, an optimized fabrication approach has been used for the preparation of PLGA and PLGA-PEG NPs loaded with docetaxel for IV application. Both types of NP formulations demonstrated in vitro characteristics that were considered suitable for IV administration (with long-circulating sustained-release purposes). NP formulations were IV administered to an animal model, and docetaxel's pharmacokinetic and biodistribution profiles were determined and compared between study groups. PLGA and PEGylated PLGA NPs were able to modify the pharmacokinetics and biodistribution of docetaxel. Accordingly, the mode of changes made to pharmacokinetics and biodistribution of docetaxel is attributed to the size and surface properties of NPs. NPs contributed to increased blood residence time of docetaxel fulfilling their role as long-circulating sustained-release drug delivery systems. Surface modification of NPs contributed to more pronounced docetaxel blood concentration, which confirms the role of PEG in conferring long-circulation properties to NPs.

  16. Dual-modality NIRF-MRI cubosomes and hexosomes: High throughput formulation and in vivo biodistribution

    International Nuclear Information System (INIS)

    Tran, Nhiem; Bye, Nicole; Moffat, Bradford A.; Wright, David K.; Cuddihy, Andrew; Hinton, Tracey M.; Hawley, Adrian M.; Reynolds, Nicholas P.; Waddington, Lynne J.; Mulet, Xavier; Turnley, Ann M.; Morganti-Kossmann, M. Cristina; Muir, Benjamin W.

    2017-01-01

    Engineered nanoparticles with multiple complementary imaging modalities are of great benefit to the rapid treatment and diagnosis of disease in various organs. Herein, we report the formulation of cubosomes and hexosomes that carry multiple amphiphilic imaging contrast agents in their self-assembled lipid bilayers. This is the first report of the use of both near infrared fluorescent (NIRF) imaging and gadolinium lipid based magnetic resonance (MR) imaging modalities in cubosomes and hexosomes. High-throughput screening was used to rapidly optimize formulations with desirable nano-architectures and low in vitro cytotoxicity. The dual-modal imaging nanoparticles in vivo biodistribution and organ specific contrast enhancement were then studied. The NIRF in vivo imaging results indicated accumulation of both cubosomes and hexosomes in the liver and spleen of mice up to 20 h post-injection. Remarkably, the biodistribution of the nanoparticle formulations was affected by the mesophase (i.e. cubic or hexagonal), a finding of significant importance for the future use of these compounds, with hexosomes showing higher accumulation in the spleen than the liver compared to cubosomes. Furthermore, in vivo MRI data of animals injected with either type of lyotropic liquid crystal nanoparticle displayed enhanced contrast in the liver and spleen. - Highlights: • Dual modality NIRF-MR imaging self-assembled lipid nanoparticles were formulated. • The nanoparticles showed cubic and hexagonal internal nanostructures. • Biodistribution experiments revealed accumulation of both cubosomes and hexosomes in spleen and liver of mice. • Pre-clinical MRI displayed enhanced contrast in spleen and liver of mice that received either cubosomes or hexosomes.

  17. Synthesis, radiolabeling and biodistribution of a new opioid glucuronide derivative. Ethyl-morphine glucuronide (em-glu)

    International Nuclear Information System (INIS)

    Enginar, H.

    2012-01-01

    In current study, ethyl-morphine (em) was synthesized from the morphine and glucuronidated via enzymatic mechanism. The conjugated glucuronide ethyl-morphine (em-glu) was radiolabeled with 131 I using iodogen method. The quality control studies of radiolabeled compound ( 131 I-em-glu) were done with Thin Layer Radio Chromatography to confirm the radiolabeling efficiency. Biodistribution studies of 131 I labeled em-glu were run on healthy male Albino Wistar rats. The distribution figures demonstrated that 131 I-em-glu was eliminated through the small intestine, large intestine and accumulated in urinary bladder both receptor blocked and unblocked biodistribution studies. A greater uptake of the radiolabeled substance was observed in the m.pons, hypothalamus and mid brain than in the other branches of the rats' brains. (author)

  18. Biodistribution, pharmacokinetics, and toxicity of dendrimer-coated iron oxide nanoparticles in BALB/c mice

    Directory of Open Access Journals (Sweden)

    Salimi M

    2018-03-01

    Full Text Available Marzieh Salimi,1,2 Saeed Sarkar,1,2 Samaneh Fathi,3 Ali Mohammad Alizadeh,4 Reza Saber,2,3 Fatemeh Moradi,5 Hamid Delavari6 1Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran; 2Research Center of Science and Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 3Department of Medical Nanotechnology, Tehran University of Medical Sciences, Tehran, Iran; 4Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran; 5Department of Medical Physiology, Tehran University of Medical Sciences, Tehran, Iran; 6Department of Materials Science and Engineering, Tarbiat Modares University, Tehran, Iran Background: The possibility of using a specific nanoparticle in nanomedicine highly depends on its biodistribution profile and biocompatibility. Due to growing demand for iron oxide nanoparticles (IONPs and dendrimers in biomedical applications, this study was performed to assess the biodistribution, pharmacokinetics, and toxicity of dendrimer-coated iron oxide nanoparticles (G4@IONPs. Materials and methods: IONPs were synthesized via co-precipitation and coated with the fourth generation (G4 of polyamidoamine (PAMAM dendrimer. To determine the biodistribution, 5 mg/mL G4@IONPs suspension was intraperitoneally injected into tumor-bearing BALB/c mice, and iron levels in blood and various organs, including the lung, liver, brain, heart, tumor, and kidney, were measured by inductively coupled plasma mass spectrometry (ICP-MS at 4, 8, 12, and 24 h after injection. Also, to investigate the toxicity of G4@IONPs, different concentrations of G4@IONPs were injected into BALB/c mice, and blood, renal, and hepatic factors were measured. Furthermore, histopathological staining was performed to investigate the effect of G4@IONPs on the liver and kidney tissues. Results: The results showed that the iron content was higher in the kidney, liver, and lung tissues 24 h after

  19. Radioiodine-labeling of EGCG and its biodistribution in mice

    International Nuclear Information System (INIS)

    Diao Yao; Zhao Wenjin; Liu Jie; Zhao Xun; Yu Chengguo; Cui Zeshi; Liu Xinning; Lan Zhenhe; Ma Jing

    2013-01-01

    To establish the 125 I-EGCG labeling method and investigate the biodistribution of 125 I-EGCG in mice, 125 I-EGCG was prepared by Iodogen solid labeling method, and were isolated and purified by Sephadex-G25 agarose. The labeling yield and radiochemical purity of 125 I-EGCG was analyzed by polyamide TLC. The labeling yield of 125 I-EGCG was 89.4% and its radiochemical purity (RCP) were 96.4%. The Biodistribution of 125 I-EGCG in mice was measured at different times after caudal vein injection with 185 kBq for each mice. The biodistribution in mice demonstrated that 125 I-EGCG was distributed into broad organs and tissues, especially in the Stomach, Small intestine and Submaxillay gland, and the biggest uptake of 125 I-EGCG in there organs was 15.92, 5.83 and 11.56 %ID · g -1 respectively at 15 min post injection. In addition, 125 I-EGCG was cleared out from blood quickly, and the uptake of 131 I-EGCG in blood was 11.95 at 5 min, and decreased to 1.25 at 4 h post injection. Therefore, 125 I-EGCG was stable and it was metabolized mainly in Stomach, Small intestine, Submaxillay gland, worthy of further investigation to trace the compound in vivo and in vitro. (authors)

  20. Whole-body biodistribution, dosimetry and metabolite correction of [11C]palmitate: A PET tracer for imaging of fatty acid metabolism

    DEFF Research Database (Denmark)

    Christensen, Nana Louise; Jakobsen, Steen; Schacht, Anna Christina

    2017-01-01

    release and parent [11C]palmitate measured by a solid-phase extraction (SPE) method. Finally, myocardial fatty acid uptake was calculated in a patient cohort using input functions derived from individual metabolite correction compared with population-based metabolite correction. RESULTS: In humans, mean......INTRODUCTION: Despite the decades long use of [11C]palmitate positron emission tomography (PET)/computed tomography in basic metabolism studies, only personal communications regarding dosimetry and biodistribution data have been published. METHODS: Dosimetry and biodistribution studies were...

  1. [Electrophysiological bases of semantic processing of objects].

    Science.gov (United States)

    Kahlaoui, Karima; Baccino, Thierry; Joanette, Yves; Magnié, Marie-Noële

    2007-02-01

    How pictures and words are stored and processed in the human brain constitute a long-standing question in cognitive psychology. Behavioral studies have yielded a large amount of data addressing this issue. Generally speaking, these data show that there are some interactions between the semantic processing of pictures and words. However, behavioral methods can provide only limited insight into certain findings. Fortunately, Event-Related Potential (ERP) provides on-line cues about the temporal nature of cognitive processes and contributes to the exploration of their neural substrates. ERPs have been used in order to better understand semantic processing of words and pictures. The main objective of this article is to offer an overview of the electrophysiologic bases of semantic processing of words and pictures. Studies presented in this article showed that the processing of words is associated with an N 400 component, whereas pictures elicited both N 300 and N 400 components. Topographical analysis of the N 400 distribution over the scalp is compatible with the idea that both image-mediated concrete words and pictures access an amodal semantic system. However, given the distinctive N 300 patterns, observed only during picture processing, it appears that picture and word processing rely upon distinct neuronal networks, even if they end up activating more or less similar semantic representations.

  2. A brain electrophysiological correlate of depth perception

    International Nuclear Information System (INIS)

    Akay, Ahmet; Celebi, Gurbuz

    2009-01-01

    To investigate brain electrical activity accompanying depth perception using random-dot stereograms. Additional experiments were conducted to ascertain the specificity of this potential to depth perception. In the present study, we performed 3 different and independent experiments on 34 subjects to establish the relationship between depth perception and its cortical electrophysiological correlate. Visual evoked potentials in response to visual stimulation by random-dot stereograms were recorded. To achieve this goal, a data acquisition and analysis system, different from common visual evoked potential recording systems, consisting of 2 personal computers, was used. One of the computers was used to generate the visual stimulus patterns and the other to record and digitally average the potentials evoked by the stimuli. This study was carried out at the Department of Biophysics of Ege University Medical School, Izmir, Turkey, from April to December, 2006. A negative potential component, which is thought to arise in association with depth perception, was recorded from the occipital region from 30 of the 34 subjects. Typically, it had a mean latency of 211.46 ms and 6.40 micron V amplitude. The negative potential is related to depth perception, as this component is present in the responses to stimulus, which carries disparity information but is absent when the stimulus is switched to no disparity information. Additional experiments also showed that the specificity of this component to depth perception becomes evident beyond doubt. (author)

  3. Preparation and standardization of an 'in vitro' labelling methodology and study of [{sup 99m} Tc]-EDDA/Tricine/Hynic-[Tyr{sup 3}]-octreotide biodistribution; Preparacao e padronizacao de metodologia de marcacao 'in vitro' e estudo de biodistribuicao do octreotideo-[Tyr{sup 3} ]Hynic/EDDA/Tricina[{sup 99m}Tc

    Energy Technology Data Exchange (ETDEWEB)

    Hernandes Melero, Laura Terumi Ueda

    2008-07-01

    .60 {+-} 0.35 % at 5 hours using 80 /{mu}g octreotide-HYNIC, 10 mg of EDDA, 20 mg of tricine, 150 {mu}g of SnCI{sub 2}.2H{sub 2}0 in a final pH 8.0, and activity up to 3700 MBq (100 mCi). This formulation can be an alternative for the administration of more than one patient per labeling procedure, using a lyophilized reagent. The biodistribution performed by invasive method in the intervals of 1.5 and 4 hours after intravenous administration of the radiopharmaceutical in Swiss mice determined the percentage of the activity administered in the blood and the various organs. The biodistribution data in Swiss and Nude mice bearing AR42J tumor (rat pancreatic adenocarcinoma) were compatible with the distribution of the labeled peptide: fast blood clearance, high uptake in the kidneys due to the elimination by the urinary tract, and high uptake in organs with high density of somatostatin receptors like lung, stomach, pancreas and tumor in the case of Nude mice. The uptake of the radiolabeled peptide in the abdominal region was not significant and represents an advantage related to the diagnosis of neuroendocrine tumors, frequently found in this region. The labeling and biodistribution results described in this study showed the potential of the {sup 99m}Tc-labeled peptide to be applied in diagnostic procedures in nuclear medicine. (author)

  4. Integrated platform and API for electrophysiological data.

    Science.gov (United States)

    Sobolev, Andrey; Stoewer, Adrian; Leonhardt, Aljoscha; Rautenberg, Philipp L; Kellner, Christian J; Garbers, Christian; Wachtler, Thomas

    2014-01-01

    Recent advancements in technology and methodology have led to growing amounts of increasingly complex neuroscience data recorded from various species, modalities, and levels of study. The rapid data growth has made efficient data access and flexible, machine-readable data annotation a crucial requisite for neuroscientists. Clear and consistent annotation and organization of data is not only an important ingredient for reproducibility of results and re-use of data, but also essential for collaborative research and data sharing. In particular, efficient data management and interoperability requires a unified approach that integrates data and metadata and provides a common way of accessing this information. In this paper we describe GNData, a data management platform for neurophysiological data. GNData provides a storage system based on a data representation that is suitable to organize data and metadata from any electrophysiological experiment, with a functionality exposed via a common application programming interface (API). Data representation and API structure are compatible with existing approaches for data and metadata representation in neurophysiology. The API implementation is based on the Representational State Transfer (REST) pattern, which enables data access integration in software applications and facilitates the development of tools that communicate with the service. Client libraries that interact with the API provide direct data access from computing environments like Matlab or Python, enabling integration of data management into the scientist's experimental or analysis routines.

  5. Radiolabeling and biodistribution of 62Cu-dithiocarbamate

    International Nuclear Information System (INIS)

    Matsumoto, Kazuya; Fujibayashi, Yasuhisa; Yokoyama, Akira; Konishi, Junji.

    1990-01-01

    The newly developed 62 Zn/ 62 Cu generator system has made available the production of the short-lived 62 Cu (T 1/2 = 9.8 min) positron radionuclide, eluted as 62 Cu-glycine. In the search for 62 Cu labeled radiopharmaceuticals for positron CT (PET) brain diagnostic studies, two ligands N,N-diethyl- and N,N-dimethyl-dithiocarbamic acid (DDC and DmDC) were selected, based on their Cu chelating abilities and the neutral lipophilic character of their copper chelates. In the present work, an in vitro study with non-radioactive Cu-glycine showed that both ligands easily formed the stable, neutral Cu-DDC and Cu-DmDC chelates (1:2 metal-ligand complexes) based on the ligand exchange reaction. Then the 62 Zn/ 62 Cu generator eluate, the 62 Cu-glycine was used for the radiolabeling of DDC and DmDC. The following HPLC analysis revealed that the ligand exchange reaction proceeded rapidly; the radiochemical purities of 62 Cu-DDC and 62 Cu-DmDC were extremely high (non-detectable 62 Cu-glycine) and both chelates were more lipophilic than 62 Cu-glycine. The mouse biodistribution of both radiolabeled compounds, 62 Cu-DDC and 62 Cu-DmDC indicated a brain accumlation of 2.8 and 5.3 times higher than 62 Cu-glycine, 15 min post injection, respectively. The brain accumulation observed with both 62 Cu-DDC and 62 Cu-DmDC might be due to their stable, neutral and lipophilic character; the latter enhanced by the presence of the methylated side chains. The gathered results indicated the applicability of dithiocarbamic acid derivatives in the production of new 62 Cu-labeled compounds using the 62 Zn/ 62 Cu generator system based on the ligand exchange reaction with 62 Cu-glycine eluate. Further studies with Cu-dithiocarbamic acid derivatives for development of new generator-produced 62 Cu positron radiopharmaceuticals can be recalled. (author)

  6. Effect of iron deficiency anemia on the biodistribution of {sup 99m}Tc radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Calmanovici, Gabriela P. [Radioisotopes Laboratory, Physics Department, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956 - 1113, Buenos Aires (Argentina); Salgueiro, Maria J. [Radioisotopes Laboratory, Physics Department, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956 - 1113, Buenos Aires (Argentina); Janjetic, Mariana A. [Physics Department, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956 - 1113, Buenos Aires (Argentina); Leonardi, Natalia M. [Radioisotopes Laboratory, Physics Department, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956 - 1113, Buenos Aires (Argentina); Boccio, Jose R. [Physics Department, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956 - 1113, Buenos Aires (Argentina); Zubillaga, Marcela B. [Radioisotopes Laboratory, Physics Department, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956 - 1113, Buenos Aires (Argentina)]. E-mail: mzubi@ffyb.uba.ar

    2006-05-15

    The distribution of colloids and labeled cells in organs is influenced by their intrinsic properties and by the state of the investigated subject. Iron deficiency remains an unsolved nutritional problem all over the world; one of its severe consequences is anemia. Because iron metabolism principally takes place in the liver, spleen, bone marrow, skeletal muscle and blood, we studied the effect of iron deficiency anemia on the biodistribution of {sup 99m}Tc phytate, {sup 99m}Tc gelatin colloid and {sup 99m}Tc RBC (red blood cells labeled with {sup 99m}Tc). Our results show that iron deficiency anemia modifies the pattern of biodistribution of the two colloids assayed. However, this behavior is different for both of them. This work contributes to studies that kinetically and statistically establish that iron deficiency anemia induces a significant inversion in the spleen-liver activity relationship when centellographic studies are performed with colloids such as {sup 99m}Tc phytate.

  7. 99mTc-glycopeptide: Synthesis, biodistribution and imaging in breast tumor-bearing rodents

    International Nuclear Information System (INIS)

    Wei, I-C.; Tsao Ning; Huang Yahui; Ho Yensheng; Wu Chungchin; Yu Dongfang; Yang, David J.

    2008-01-01

    This study was aimed to develop a glycopeptide (GP) to be used as a carrier for anti-cancer drug delivery. GP was synthesized by conjugating glutamate peptide and chitosan using carbodiimide as a coupling agent. Elemental analysis and capillary electrophoresis confirmed the purity was >95%. GP was labeled with sodium pertechnetate (Na 99m TcO 4 ) for in vitro and in vivo studies. Rhenium-GP was synthesized to support the binding site of 99m Tc at the glutamate positions 3-5. In vitro cellular uptake of 99m Tc-GP was performed in breast cancer cells. Cytosol had 60% whereas nucleus had 40% uptake of 99m Tc-GP. When cancer cells were incubated with glutamate or aspartate, followed by 99m Tc-GP, there was decreased uptake in cells treated with glutamate but not aspartate. The findings indicated that cellular uptake of 99m Tc-GP was via glutamate transporters. In addition, 99m Tc-GP was able to measure uptake differences after cells treated with paclitaxel. Biodistribution and planar imaging were conducted in breast tumor-bearing rats. Biodistribution of 99m Tc-GP showed increased tumor-to-tissue ratios as a function of time. Planar images confirmed that 99m Tc-GP could assess tumor uptake changes after paclitaxel treatment. In vitro and in vivo studies indicated that GP could target tumor cells, thus, GP may be a useful carrier for anti-cancer drug delivery

  8. Differential biodistribution of oncolytic poxvirus administered systemically in an autochthonous model of hepatocellular carcinoma.

    Science.gov (United States)

    Baril, Patrick; Touchefeu, Yann; Cany, Jeannette; Cherel, Yan; Thorne, Steve H; Tran, Lucile; Conchon, Sophie; Vassaux, Georges

    2011-12-01

    Preclinical studies have demonstrated that, unlike oncolytic adenoviruses, oncolytic vaccinia viruses can reach implanted tumors upon systemic injection. However, the biodistribution of this oncolytic agent in in situ autochthonous tumor models remains poorly characterized. In the present study, we assessed this biodistribution in a model of mouse hepatocellular carcinoma (HCC) obtained after injection of the carcinogen diethylnitrosamine (DEN). Twelve months after DEN administration, histology, quantitative reverse transcription-polymerase chain reaction, in situ hybridization and viral titration were used to characterize tumors, as well as to assess the viral load of the livers upon either intravenous or intraperitoineal injection. The results obtained showed that the architecture of the liver was lost, with a noticeable absence of sinusoids, as well as the presence of steatosis and α-fetoprotein-positive HCC tumor nodules. Bioluminescence imaging and measures of the infective virus load demonstrated that intravenous injection of 10(8)  plaque-forming units of the recombinant vaccinia virus led to a predominant transduction of the liver, whereas intraperitoneal injection resulted in a lower level of liver transduction accompanied by an increased infection of the lungs, spleen, kidneys and bowels. Immunohistochemical analysis of liver sections of animals injected intravenously with the virus revealed a preferential localization of vaccinia-specific immunoreactivity in the tumors. The findings of the present study emphasize the importance of the route of administration of the vector and highlight the relevance of systemic injection of oncolytic vaccinia virus in the context of hepatocellular carcinoma. Copyright © 2011 John Wiley & Sons, Ltd.

  9. I-124 production using nanomaterials and its biodistribution in animals

    International Nuclear Information System (INIS)

    Braghirolli, Ana Maria Silveira

    2014-01-01

    Iodine-124 is a positron emitter with physical half-life of 4.2 days. Its decay occurs by positron emission (23.3%) and electron capture (76.7%). Their physical and chemical characteristics make it an attractive isotope for medical applications. The development of new imaging techniques, improvements in Positron Emission Tomography (PET), the development of new detectors and computational methods of signal processing, open new perspectives for its application. The increasing use of PET technology in medical oncology, pharmacokinetics and drug metabolism, make the radiopharmaceuticals labeled with 124 I a tool of great interest and usefulness. The use of 124 I - labeled molecules stands out particularly due to the convenient half-life of 124 I. This feature enables diagnostic imaging in PET centers far away from the radionuclides producing center. Within this context, this work presents a method for the production and separation of 124 I. This method is innovative and pioneering in the country. It is based on the development and use of nanostructured targets of nat TeO 2 . These targets are irradiated in a charged particles accelerator, with variable energy, the IEN's CV-28 cyclotron. The irradiations are performed with 24 MeV, initial energy, proton beams. In the preparation of nanoparticulated targets the highlight was the simplicity of the method that uses the sol-gel technique for obtaining nanoparticles, TeCl 4 as precursor and water as solvent. The produced 124 I was separated from the target material by dry distillation and trapped in a NaOH solution (0.02 M), in an automated system. The thick target yield was 6.81 MBq/μAh, and the synthesis yield was 90%. The 124 I obtained was then used in preliminary biodistribution studies. These studies were performed on a micro PET, model Lab PET 4 of the CDTN, in Swiss type mice. The results of the application of Na 124 I showed high quality PET imaging of the thyroid, with the maximum uptake at 6 h after

  10. In vivo biodistribution of 131I labeled bleomycin (BLM) and isomers (A2 and B2) on experimental animal models

    International Nuclear Information System (INIS)

    Avcibasi, U.; Demiroglu, H.; Uenak, P.; Mueftueler, F.Z.B.; Ichedef, C.A.; Guemueser, F.G.

    2010-01-01

    Bleomycins (BLMs; BLM, A2, and B2) were labeled with 131 I and radiopharmaceutical potentials were investigated using animal models in this study. Quality control procedures were carried out using thin layer radiochromatography (TLRC), high performance liquid chromatography (HPLC), and liquid chromatography (LC/MS/MS). Labeling yields of radiolabeled BLMs were found to be 90, 68, and 71%, respectively. HPLC chromatograms were taken for BLM and cold iodinated BLM ( 127 I-BLM). Five peaks were detected for BLM and three peaks for 127 I-BLM in the HPLC studies. Two peaks belong to isomers of BLM. The isomers of BLM were purified with using HPLC. Biological activity of BLM was determined on male Albino Wistar rats by biodistribution and scintigraphic studies were performed for BLMs by using New Zealand rabbits. The biodistribution results of 131 I-BLM showed high uptake in the stomach, the bladder, the prostate, the testicle, and the spinal cord in rats. Scintigraphic results on rabbits agrees with that of biodistributional studies on rats. The scintigraphy of radiolabeled isomers ( 131 I-A2 and 131 I-B2) are similarly found with that of 131 I-BLM. (author)

  11. Effects of Glycosylation on Biodistribution and Imaging Quality of Necrotic Myocardium of Iodine-131-Labeled Sennidins.

    Science.gov (United States)

    Li, Ling; Zhang, Dongjian; Yang, Shengwei; Song, Shaoli; Li, Jindian; Wang, Qin; Wang, Cong; Feng, Yuanbo; Ni, Yicheng; Zhang, Jian; Liu, Wei; Yin, Zhiqi

    2016-12-01

    Sennidins are necrosis-avid agents for noninvasive assessment of myocardial viability which is important for patients with myocardial infarction (MI). However, high accumulation of radioactivity in the liver interferes with the assessment of myocardial viability. In this study, we compared sennidins with sennosides to investigate the effects of glycosylation on biodistribution and imaging quality of sennidins. Sennidin A (SA), sennidin B (SB), sennoside A (SSA), and sennoside B (SSB) were labeled with I-131. In vitro binding to necrotic cells and hepatic cells and in vivo biodistribution in rats with muscular necrosis were evaluated by gamma counting, autoradiography, and histopathology. Single photon emission computed tomography/computed tomography (SPECT/CT) images were acquired in rats with acute MI. The uptake of [ 131 I]SA, [ 131 I]SSA, [ 131 I]SB, and [ 131 I]SSB in necrotic cells was significantly higher than that in viable cells (p sennosides than those with [ 131 I]sennidins (p < 0.01). Autoradiography showed preferential accumulation of these four radiotracers in necrotic areas of muscle, confirmed by histopathology. SPECT/CT imaging studies showed better image quality with [ 131 I]SSB than with [ 131 I]SB due to less liver interference. Glycosylation significantly decreased the liver uptake and improved the quality of cardiac imaging. [ 131 I]SSB may serve as a promising necrosis-avid agent for noninvasive assessment of myocardial viability.

  12. Radioiodination and biodistribution of isolated lawsone compound from Lawsonia inermis (henna) leaves extract

    International Nuclear Information System (INIS)

    Volkan Tekin; Zumrut Biber Muftuler, F.; Ayfer Yurt Kilcar; Perihan Unak

    2014-01-01

    Lawsonia inermis (henna) is one of the most effective medicinal plants and it has been using for treatment of wounds and burns for centuries. The using of Henna leaves is very popular for cosmetic as well as medicine in many countries. Henna leaves contain lots of different compounds and lawsone (LW) is the main one. In current study, extraction with bidistillated water of henna leaves was performed and LW was isolated by using high performance liquid chromatography system. Chemical structure of LW was evaluated by nuclear magnetic resonance method. LW was radiolabeled with iodine-131 ( 131 I) radionuclide which is well known for nuclear imaging and therapy in nuclear medicine by utilizing iodogen method. The yield of radiolabeling of LW ( 131 I-LW) was calculated as 92.70 ± 4.312 % (n = 10) by thin layer radio chromatography. Its in vivo biological activity was investigated by biodistribution studies which were performed by using healthy female and male Balb/C mice. According to results of biodistribution, uptake of 131 I labeled LW compound in uterus, breast and ovary for female mice and prostate in male mice was higher than other organs in the body. (author)

  13. In vivo evaluation of potential Tc-99m brain perfusion agents using brain uptake index determination and biodistribution

    International Nuclear Information System (INIS)

    Rajeckas, A.J.; Watson, A.D.; Subramanyam, V.; Williams, S.J.; Belonga, B.Q.; de Nemours, E.I.D.

    1985-01-01

    In order to evaluate the pharmacological properties of various Tc-99m complexes as potential brain perfusion agents, the authors have employed both biodistribution techniques as well as modified Oldendorf procedure for the determination of the brain uptake index (BUI). A typical BUI determination involves the coinjection of 1 microcurie each of I-125 iodoantipyrine and the Tc-99m complex into the left carotid artery of a pentabarbitol anesthetized rat. The animal is sacrificed at 10 seconds; the right and left hemispheres of the brain are removed and counted for each isotope in a gamma well counter. Biodistribution studies are performed using tail-vein injections in unanesthetized rats. In the evaluation of a series of Tc-99m N/sub 2/S/sub 2/ (diamine dithiol) complexes, they have observed that compounds with a low BUI (less than 50) also have a low brain concentration (less than 1% ID) at 30 seconds post injection

  14. Synthesis quality control and biodistribution of technetium-99m triamcinolone (99mTc-TA) complex: An inflammation tracer agent

    International Nuclear Information System (INIS)

    Rizvii, Faheem Askari; Naqvi, Syed Ali Raza; Mehdi, Muhammad; Roohi, Samina; Zahoor, Ameer Fawad; Khan, Zulfiqar Ali; Sohaib, Muhammad; Rasheed, Rashid

    2017-01-01

    In present study synthesis of 99m Tc-triamcinolone acetonide ( 99m Tc-TA) complex and its stability using set of quality control parameters such as ligand concentration, reducing agent concentration, pH, temperature and reaction time was assessed. 99m Tc-TA complex was characterized in terms of percent (%) yield, stability in saline and serum using chromatographic procedures. Radiochemically the 99m Tc-TA complex was found quite stable in saline and serum. After 30 min of reaction the complex showed maximum radiochemical yield of 96.32% which decreased to 96.25 % after 4 h incubation period. In serum, the % yield of radiochemical was remained same up to 2 h which decreased to 93.5% at 24 h time point. Normal biodistribution pattern in Sprague-Dawley rats revealed liver, stomach and kidneys as areas of high 99m Tc-TA complex uptake (8.44 ±1.32, 8.75 ± 1.03 and 12.67 ± 1.21%, respectively) at 1 h post injection time point. Scintigraphy of 99m Tc-TA in rabbits showed similar eco as observed in biodistribution study. Based on the promising results obtained in context of in vitro and in vivo stability and biodistribution, 99m Tc-TA complex could be further studied to identify the inflammation based diseases

  15. Preparation, quality control and biodistribution of [61Cu]-doxorubicin for PET imaging

    International Nuclear Information System (INIS)

    Jalilian, A.R.; Akhlaghi, M.; Zandi, H.; Yousefnia, H.; Faghihi, R.

    2009-01-01

    This work was conducted for radiolabeling of an anticancer antibiotic, i.e. doxorubicin with 61 Cu for production of possible tracer used in PET oncology. 61 Cu was prepared with natural zinc target and 22 MeV 150 μA protons via nat Zn(p, xn) 61 Cu reaction with a yield of 123.2 MBq·μA -1 ·h -1 . Optimization reactions were performed for pH, temperature and concentration. Biodistribution of the tracer was studied in normal and fibrosarcoma bearing mice. At the optimized conditions, ITLC showed that radiochemical purity was over 97% with a specific activity of 2.22 X 10 3 MBq·mmol -1 ·L -1 . This was kept unchanged even with presence of human serum as well as room temperature for 5 h. Biodistribution of the tracer in fibrosarcoma bearing mice demonstrated significant tumor uptake after 2 h. This tracer can be used in the detection of various tumors responding to doxorubicin chemotherapy using PET scan and/or determination of tumor therapy response to doxorubicin chemotherapy. (authors)

  16. Molecular Imaging of Stem Cells: Tracking Survival, Biodistribution, Tumorigenicity, and Immunogenicity

    Directory of Open Access Journals (Sweden)

    Eugene Gu, Wen-Yi Chen, Jay Gu, Paul Burridge, Joseph C. Wu

    2012-01-01

    Full Text Available Being able to self-renew and differentiate into virtually all cell types, both human embryonic stem cells (hESCs and induced pluripotent stem cells (iPSCs have exciting therapeutic implications for myocardial infarction, neurodegenerative disease, diabetes, and other disorders involving irreversible cell loss. However, stem cell biology remains incompletely understood despite significant advances in the field. Inefficient stem cell differentiation, difficulty in verifying successful delivery to the target organ, and problems with engraftment all hamper the transition from laboratory animal studies to human clinical trials. Although traditional histopathological techniques have been the primary approach for ex vivo analysis of stem cell behavior, these postmortem examinations are unable to further elucidate the underlying mechanisms in real time and in vivo. Fortunately, the advent of molecular imaging has led to unprecedented progress in understanding the fundamental behavior of stem cells, including their survival, biodistribution, immunogenicity, and tumorigenicity in the targeted tissues of interest. This review summarizes various molecular imaging technologies and how they have advanced the current understanding of stem cell survival, biodistribution, immunogenicity, and tumorigenicity.

  17. Biodistribution and catabolism of 18F-labelled isopeptide N(epsilon)-(gamma-glutamyl)-L-lysine.

    Science.gov (United States)

    Hultsch, C; Bergmann, R; Pawelke, B; Pietzsch, J; Wuest, F; Johannsen, B; Henle, T

    2005-12-01

    Isopeptide bonds between the epsilon-amino group of lysine and the gamma-carboxamide group of glutamine are formed during strong heating of pure proteins or, more important, by enzymatic reaction mediated by transglutaminases. Despite the wide use of a microbial transglutaminase in food biotechnology, up to now little is known about the metabolic fate of the isopeptide N(epsilon)-(gamma-glutamyl)-L-lysine. In the present study, N-succinimidyl-4-[(18)F]fluorobenzoate was used to modify N(epsilon)-(gamma-glutamyl)-L-lysine at each of its two alpha-amino groups, resulting in the 4-[(18)F]fluorobenzoylated derivatives, for which biodistribution, catabolism, and elimination were investigated in male Wistar rats. A significant different biochemical behavior of the two labelled isopeptides was observed in terms of in vitro stability, in vivo metabolism as well as biodistribution. The results suggest that the metabolic fate of isopeptides is likely to be dependent on how they are reabsorbed - free or peptide bound.

  18. Ciprofloxacin-99mTc: labeling and biodistribution in infection diagnostic

    International Nuclear Information System (INIS)

    Martins, Patricia de Andrade

    2004-01-01

    Labeling and biodistribution studies with the antibiotic ciprofloxacin were done using as radio marker Tc-99m. The aims were to optimize the labeling procedures as well as to analyze its efficacy in the diagnosis of infection sites, healthy and experimentally infected animals were employed to this purpose. On basis of optimized parameters a freeze-dried could be formulated containing 2 mg ciprofloxacin, 30 μg SnCl 2 H O and 5 mg ascorbic acid. This preparation could be easily activated by the addiction of Na 99m Tc) 4 a maximum value of 3700 MBq after a reaction time of 10 minutes only. Yield of the labeling technique higher than 95%, radiochemical stability reached 6 hours after preparation, and shelf life till 2 months was demonstrated. Biodistribution investigations revealed high renal excretion, low concentration in liver and soft tissues, along with affinity for the bacterial focus 1.7-2.4 times higher than for normal tissues. This protocol demonstrated the potential of ciprofloxacin- 99m Tcs a diagnostic agent for infections process. (author)

  19. Labelling and biodistribution of /sup 99m/Tc-ceftriaxone: a new imaging agent

    International Nuclear Information System (INIS)

    Khurshid, Z.; Roohi, S.; Zahoor, R.; Tariq, S.

    2012-01-01

    Most commonly used infection imaging agents are specific for inflammation. Some newer agents like labeled antimicrobials and peptides have shown infection seeking properties. Research is underway for synthesis of newer imaging agents specific for infections. In this quest we have labeled and bio evaluated /sup 99m/Tc-ceftriaxone. Ceftriaxone is a commonly used third generation cephalosporin antibiotic having a broad anti-bacterial spectrum but has more specificity for gram-negative bacteria. /sup 99m/Tc-ceftriaxone was prepared at ph 7 by adding 30 mg of ligand to /sup 99m/Tc in the presence of 50 mu g of SnCl/sub 2/./sup 2/H/sub 2/O. Boiling for ten minutes gave maximum labeling yield (96+1.76%). The stability at room temperature both with and without human serum was more than 90% till 24 hours. In-vitro binding revealed maximum binding of 68% and 47% with E.coli and S.aureus respectively after 4 hours incubation. Biodistribution studies in normal rats showed maximum uptake in hepatobiliary system followed by kidney. In infection and inflammation models the maximum target to non- target ratios of 12.66 +- 2.59, 2.36 +- 0.30 and 1.44 +- 0.53 were achieved with E. coli, S. aureus and oil inflammation respectively 4 hours post injection. Scintigraphic findings also correlated with biodistribution results. (Orig./A.B.)

  20. Peripheral Neuropathy – Clinical and Electrophysiological Considerations

    Science.gov (United States)

    Chung, Tae; Prasad, Kalpana; Lloyd, Thomas E.

    2013-01-01

    This article is a primer on the pathophysiology and clinical evaluation of peripheral neuropathy for the radiologist. Magnetic resonance neurography (MRN) has utility in the diagnosis of many focal peripheral nerve lesions. When combined with history, examination, electrophysiology, and laboratory data, future advancements in high-field MRN may play an increasingly important role in the evaluation of patients with peripheral neuropathy. PMID:24210312

  1. Radioiodine-labeling of tetrahydropalmatine and its biodistribution in mice

    International Nuclear Information System (INIS)

    Tan Cheng; Lin Xiufeng; Zhang Li; Chen Bo; Cao Guoxian; Yu Huixin; Song Cuicui

    2008-01-01

    The work was to investigate radioiodinated tetrahydropalmatine and its biodistribution in mice. Tetrahydropalmatine was labeled with 131 I using the chloramine-T method and the labeled compound were characterized by polyamide TLC. The animals were sacrificed at different times after radiopharmaceutical i.v. administration. The interested tissues samples were collected, and percent injected dose per gram (%ID·g -1 ) was calculated for each sample. The labeling yield of 131 I-tetrahydropalmatine was 76% and its RCPs were 97.3%, 95.4%, and 96.8% after 1, 7 and 20 days, respectively. Biodistribution in mice demonstrated that 131 I-tetrahydropalmatine was extensive, and it was metabolized mainly in liver and kidney, which contained of 14.35% and 6.55% ID·g -1 at 5 min, respectively, with 3.26% and 1.20% ID·g -1 at 4h, respectively. Comparatively high 131 I-tetrahydropalmatine was found in intestine and fat, but clearance was slow, 3.91% and 3.05% at 5 min and decreased to 0.79% and 0.37% at 4 h. The results also showed that 131 I-tetrahydropalmatine could well penetrate the blood-brain barrier to attain a maximal level in brain tissue within 5-10 min, but it mostly was cleaned out after 2 h. There was no significant difference in brain regions despite of highest biodistribution in parietal lobe. In conclusion, 131 I-tetrahydropalmatine was stable and it was metabolized mainly in liver and kidney, but there was no significant difference in brain regions. (authors)

  2. Biodistribution of technetium-{sup 99m} pertechnetate after Roux-en-Y gastric bypass (Capella technique) in rats

    Energy Technology Data Exchange (ETDEWEB)

    Rego, Amalia Cinthia Meneses do; Jacome, Daniel Torres; Ramalho, Rachel de Alcantara Oliveira [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil); Araujo-Filho, Irami; Azevedo, Italo Medeiros; Medeiros, Aldo Cunha, E-mail: aldo@ufrnet.b [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Dept. of Surgery

    2010-01-15

    Purpose: The biodistribution of sodium pertechnetate, the most used radiopharmaceutical in nuclear medicine, has not been studied in details after bariatric surgery. The objective was to investigate the effect of Roux-en-Y gastric bypass (RYGB) on biodistribution of sodium pertechnetate (Na{sup 99m}Tc-) in organs and tissues of rats. Methods: Twelve rats were randomly divided into two groups of 6 animals each. The RYGB group rats were submitted to the Roux-en-Y gastric bypass and the control group rats were not operated. After 15 days, all rats were injected with 0.1mL of Na{sup 99m}Tc- via orbital plexus with average radioactivity of 0.66 MBq. After 30 minutes, liver, stomach, thyroid, heart, lung, kidney and femur samples were harvested, weighed and percentage of radioactivity per gram (%ATI/g) of each organ was determined by gamma counter Wizard Perkin-Elmer. We applied the Student t test for statistical analysis, considering p<0.05 as significant. Results: Significant reduction in mean %ATI/g was observed in the liver, stomach and femur in the RYGB group animals, compared with the control group rats (p<0.05). In other organs no significant difference in %ATI/g was observed between the two groups. Conclusion: This work contributes to the knowledge that the bariatric surgery RYGB modifies the pattern of biodistribution of Na{sup 99m}Tc{sup -}. (author)

  3. Encoding and Decoding Models in Cognitive Electrophysiology

    Directory of Open Access Journals (Sweden)

    Christopher R. Holdgraf

    2017-09-01

    Full Text Available Cognitive neuroscience has seen rapid growth in the size and complexity of data recorded from the human brain as well as in the computational tools available to analyze this data. This data explosion has resulted in an increased use of multivariate, model-based methods for asking neuroscience questions, allowing scientists to investigate multiple hypotheses with a single dataset, to use complex, time-varying stimuli, and to study the human brain under more naturalistic conditions. These tools come in the form of “Encoding” models, in which stimulus features are used to model brain activity, and “Decoding” models, in which neural features are used to generated a stimulus output. Here we review the current state of encoding and decoding models in cognitive electrophysiology and provide a practical guide toward conducting experiments and analyses in this emerging field. Our examples focus on using linear models in the study of human language and audition. We show how to calculate auditory receptive fields from natural sounds as well as how to decode neural recordings to predict speech. The paper aims to be a useful tutorial to these approaches, and a practical introduction to using machine learning and applied statistics to build models of neural activity. The data analytic approaches we discuss may also be applied to other sensory modalities, motor systems, and cognitive systems, and we cover some examples in these areas. In addition, a collection of Jupyter notebooks is publicly available as a complement to the material covered in this paper, providing code examples and tutorials for predictive modeling in python. The aim is to provide a practical understanding of predictive modeling of human brain data and to propose best-practices in conducting these analyses.

  4. Bioavailability and biodistribution of nanodelivered lutein

    Science.gov (United States)

    The aim of the study was to evaluate the ability of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to enhance lutein bioavailability. The bioavailability of free lutein and PLGA-NP lutein in rats was assessed by determining plasma pharmacokinetics and deposition in selected tissues. Lutein ...

  5. Biodistribution of Carbon Nanotubes in Animal Models

    DEFF Research Database (Denmark)

    Jacobsen, Nicklas Raun; Møller, Peter Horn; Clausen, Per Axel

    2017-01-01

    the main sites of long-term CNT accumulation, which also includes pleura, a major site for fibre-induced pulmonary diseases. Studies on intravenous injection show that CNT in blood circulation are cleared relatively fast with a half-life of minutes or hours. The major target organs were the same...

  6. Th biodistribution in internal contamination of animals

    International Nuclear Information System (INIS)

    Ciubotariu, M.; Danis, A.; Dumitrescu, G.; Cucu, M.

    1999-01-01

    Fissionable elements (U,Th) internal contamination have been studied using the fission track method as analysis method of the U and/or Th contaminant elements and Wistar-London breed rats as experiment animals. Different ways to obtain internal contaminations have been investigated: ingestion, inhalation, absorption by skin and through wounds. After the U internal contamination study was carried out, in this stage the Th internal contamination by ingestion is in progress. Using the identical aliquot parts of a solution calibrated in Th, corresponding to an Annual Limit Intake, three Wistar-London breed rats were contaminated. They were kept in normal life conditions and under permanent medical surveillance up to their sacrification. The animals were sacrificed at different time intervals after their contamination: 2 days, 7 days and 14 days, respectively. After the sacrification, their vital organs were sampled, weighed, calcined, re-weighed and finally analysed by track detection using the fission track micro-mappings technique. Also, their evacuations were sampled every 24 hours weighed, calcined and analysed in the same way as the vital organs. The Th fission track micro-mappings technique was used in the following conditions: - mica-muscovite as track detector pre-etched for fossil tracks 18 h in HF-40 per cent at room temperature; - the neutron irradiations were performed in the nuclear reactor VVR-S Bucharest at the neutron fluences of 3.10 15 - 2.10 16 fast neutrons/c m 2 ; - the visualization of the Th induced fission tracks were obtained by chemical etching in HF-40 per cent, 3 h at room temperature; - the Th track micro-mappings obtained in track detectors were studied by optical microscopy using a stereo microscope WILD M7S for ensemble study (X6-X31) and a binocular ZEISS JENA microscope for qualitative and quantitative studies (X150). The biological reference materials calibrated in Th were prepared in our laboratory using the calcined organs and the

  7. Safety, Pharmacokinetics, Immunogenicity, and Biodistribution of (186)Re-Labeled Humanized Monoclonal Antibody BIWA 4 (Bivatuzumab( in Patients with Early-Stage Breast Cancer.

    NARCIS (Netherlands)

    Koppe, M.; Schaijk, F. van; Roos, J.C.; Leeuwen, P.; Heider, K.H.; Kuthan, H.; Bleichrodt, R.P.

    2004-01-01

    The aim of this prospective study was to evaluate the safety, pharmacokinetics, immunogenicity, and biodistribution of (186)Re-labeled humanized anti-CD44v6 monoclonal antibody (MAb( BIWA 4 (Bivatuzumab( in 9 patients with early-stage breast cancer. Radioimmunoscintigraphy (RIS( was performed within

  8. Synthesis and biodistribution of some radioiodinated diamines

    International Nuclear Information System (INIS)

    Joshua, A.V; Sandfor, J.G.; Scott, J.R.; Muddukrishna, S.N.

    1987-01-01

    It was felt that investigations of somke side chain analogues of HIPDM [N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodo-benzyl)-1,3-propanediamine] may help elucidate some of the factors necessary for the uptake and retention of radiolabelled compounds by the brain. All compounds investigated showed significant initial brain uptake in mice. When the side chain is shortened by one carbon, there is high initial brain activity but this falls very rapidly. These results indicate that the particular side chain seen in HIPDM is important for brain retention. Several of the compounds which are reporting here, have also pancreatic uptake and the study in mece and rats are included. (M.E.L.) [es

  9. Samarium oxide as a radiotracer to evaluate the in vivo biodistribution of PLGA nanoparticles

    CSIR Research Space (South Africa)

    Mandiwana, V

    2015-09-01

    Full Text Available the biodistribution of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles containing samarium-153 oxide ([(sup153)Sm]Sm(sub2)O(sub3)) in vivo to prove that orally administered nanoparticles alter the biodistribution of a drug. These were then activated in a nuclear...

  10. Electrophysiological Evaluation of People With Volatile Substance Addiction

    Directory of Open Access Journals (Sweden)

    Nurten Uzun

    2008-02-01

    Full Text Available OBJECTIVE: Scientific BACKGROUND: There is an increase in addiction of volatile substances in recent years. Miscellaneous electrophysiological pathological findings are determined in volatile substance abusers. OBJECTIVE: In this study, we aim to examine the neurologic effects of these substances by electrophysiologic methods. METHODS: Cases and METHOD: Twenty-three patients from Bakirkoy Psychiatry Hospital, Alcohol and Substance Addiction Research and Treatment Center were included in this study. Motor and sensory nerve conduction studies, somatosensorial, visual and auditory evoked potentials (SEP, VEP, BAEP as well as electroencephalography (EEG were studied in all 23 patients. The results were compared with the published data and the values of age matched 19 normal controls. RESULTS: RESULTS: In nerve conduction studies, there were pathological findings in 14 (60.9% cases, in three (13% mild sensorimotor polyneuropathy was determined. Tibial nerve motor distal latencies as well as median nerve sensorial and sural nerve distal latencies were longer in patients compared to controls (p<0.05. SEP findings were pathological in six (26.1% cases, VEP in two (8.7% cases and BAEP in eight (34.8% cases. Scalp SEP distal latency by tibial nerve stimulation as well as distal latencies of right and left V. wave, left III-V interpeak latency, right and left interpeak latencies and I-V interaural latency difference in BAEP were longer in abusers (p<0.05. Although it was not statistically significant, the ratio of pathological findings was higher if the exposure time was over 2 years. EEG was found to be normal in all patients. CONCLUSION: YORUM: Our results showed that toluene results in slowly progressive multifocal central nervous system damage and subclinical damage could be determined in early stages by electrophysiologic methods

  11. Denervation syndromes of the shoulder girdle: MR imaging with electrophysiologic correlation

    International Nuclear Information System (INIS)

    Bredella, M.A.; Wischer, T.K.; Stork, A.; Genant, H.K.; Tirman, P.F.J.; Fritz, R.C.

    1999-01-01

    Objective. To investigate the use of MR imaging in the characterization of denervated muscle of the shoulder correlated with electrophysiologic studies.Design and patients. We studied with MR imaging five patients who presented with shoulder weakness and pain and who underwent electrophysiologic studies. On MR imaging the distribution of muscle edema and fatty infiltration was recorded, as was the presence of masses impinging on a regional nerve.Results. Acute/subacute denervation was best seen on T2-weighted fast spin-echo images with fat saturation, showing increased SI related to neurogenic edema. Chronic denervation was best seen on T1-weighted spin-echo images, demonstrating loss of muscle bulk and diffuse areas of increased signal intensity within the muscle. Three patients showed MR imaging and electrophysiologic findings of Parsonage Turner syndrome. One patient demonstrated an arteriovenous malformation within the spinoglenoid notch, impinging on the suprascapular nerve with associated atrophy of the infraspinatus muscle. The fifth patient demonstrated fatty atrophy of the teres minor muscle caused by compression by a cyst of the axillary nerve and electrophysiologic findings of an incomplete axillary nerve block.Conclusion. MR imaging is useful in detecting and characterizing denervation atrophy and neurogenic edema in shoulder muscles. MR imaging can provide additional information to electrophysiologic studies by estimating the age (acute/chronic) and identifying morphologic causes for shoulder pain and atrophy. (orig.)

  12. Iatrogenic alterations in the biodistribution of radiotracers as a result of drug therapy: Reported instances

    International Nuclear Information System (INIS)

    Hladik, W.B. III; Ponto, J.A.; Lentle, B.C.; Laven, D.L.

    1987-01-01

    This chapter is a compilation of reported instances in which the biodistribution of a radiopharmaceutical has been (or could be) modified by the administration of a therapeutic nonradioactive drug or contrast agent in such a way as to potentially interfere with the interpretation of the nuclear medicine study in question. This type of phenomenon is commonly referred to as a drug-radiopharmaceutical interaction. In this chapter, interactions are arranged according to the radiopharmaceutical involved; each interaction is characterized by use of the following descriptors: 1. Interfering drug: the interfering nonradioactive drug that alters the kinetics of the radiopharmaceutical and thus changes the resulting diagnostic data obtained from the study. 2. Nuclear medicine study affected: the nuclear medicine study in which the interaction is likely to occur. 3. Effect on image: the appearance of the image (or the effect on diagnostic data) which results from the interaction. 4. Significance: the potential clinical significance of the interaction

  13. Prevalence of ulnar-to-median nerve motor fiber anastomosis (Riché-Cannieu communicating branch) in hand: An electrophysiological study

    Science.gov (United States)

    Ahadi, Tannaz; Raissi, Gholam Reza; Yavari, Masood; Majidi, Lobat

    2016-01-01

    Background: Two main muscles studied in the hand for evaluation of median nerve injuries are opponens pollicis (OP) and abductor pollicis brevis (APB). However, Riché-Cannieu communicating branch (RCCB) may limit the use of these muscles in electrodiagnosis. This condition is confusing in the case of median nerve injuries. This study was conducted to evaluate the prevalence of RCCB. Methods: Twenty-three consecutive cases of complete median nerve injury were studied. Evoked responses via stimulation of median and ulnar nerves in the wrist and recording with needle in the thenar area were studied. Results: Of the patients, 82.6% exhibited RCCB. In 14 (60.8%) cases the OP and in 19(82.6%) cases APB was supplied by the ulnar nerve. Conclusion: RCCB was detected to be 60.8% in OP and 82.6% in APB, so OP is preferable to APB in the study of median nerve. PMID:27390694

  14. Re-visiting the electrophysiology of language.

    Science.gov (United States)

    Obleser, Jonas

    2015-09-01

    This editorial accompanies a special issue of Brain and Language re-visiting old themes and new leads in the electrophysiology of language. The event-related potential (ERP) as a series of characteristic deflections ("components") over time and their distribution on the scalp has been exploited by speech and language researchers over decades to find support for diverse psycholinguistic models. Fortunately, methodological and statistical advances have allowed human neuroscience to move beyond some of the limitations imposed when looking at the ERP only. Most importantly, we currently witness a refined and refreshed look at "event-related" (in the literal sense) brain activity that relates itself more closely to the actual neurobiology of speech and language processes. It is this imminent change in handling and interpreting electrophysiological data of speech and language experiments that this special issue intends to capture. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Labeling of scorpion venom with 99mTc and its biodistribution

    International Nuclear Information System (INIS)

    Amin, A.M.

    2013-01-01

    Labeling of scorpion venom (SV) was successfully achieved with 99m Tc using direct chelating method. Venom was labeled with 99m Tc using stannous chloride as reducing agent. Preliminary studies were done to establish the optimum conditions for obtaining the highest yield of the labeled venom. The labeling technique is effective, as a maximum labeling yield (97 %) was obtained after 30-min reaction time by using 80 μg SV in phosphate buffer of pH 7 and 25 μg Sncl 2 ·2H 2 O at room temperature. Venom was injected into normal mice to determine the excretion pathway. Biodistribution studies in normal mice with SV shows rapid clearance of the venom from blood and tissue except for kidneys. The improvement of the immunotherapeutic treatment of envenomation requires a better knowledge of the biological actions of the SV since tissue distribution studies are very important for clinical purpose. (author)

  16. In vivo biodistribution and biological impact of injected carbon nanotubes using magnetic resonance techniques

    Directory of Open Access Journals (Sweden)

    Achraf Al Faraj

    2011-02-01

    Full Text Available Achraf Al Faraj1,2, Florence Fauvelle3, Nathalie Luciani4, Ghislaine Lacroix5, Michael Levy4, Yannick Crémillieux1, Emmanuelle Canet-Soulas1Université Lyon1, Créatis-LRMN, Lyon, France; 2King Saud University, College of Applied Medical Sciences, Radiological Sciences Department, Riyadh, Kingdom of Saudi Arabia; 3CRSSA, Biophysique Cellulaire et Moléculaire, Laboratoire de RMN, La Tronche, France; 4Université Paris7-Paris Diderot, Matières et Systèmes Complexes, Paris, France; 5Institut National de l’Environnement et des Risques Industriels, Verneuil-en-Halatte, FranceBackground: Single-walled carbon nanotubes (SWCNT hold promise for applications as contrast agents and target delivery carriers in the field of nanomedicine. When administered in vivo, their biodistribution and pharmacological profile needs to be fully characterized. The tissue distribution of carbon nanotubes and their potential impact on metabolism depend on their shape, coating, and metallic impurities. Because standard radiolabeled or fluorescently-labeled pharmaceuticals are not well suited for long-term in vivo follow-up of carbon nanotubes, alternative methods are required.Methods: In this study, noninvasive in vivo magnetic resonance imaging (MRI investigations combined with high-resolution magic angle spinning (HR-MAS, Raman spectroscopy, iron assays, and histological analysis ex vivo were proposed and applied to assess the biodistribution and biological impact of intravenously injected pristine (raw and purified and functionalized SWCNT in a 2-week longitudinal study. Iron impurities allowed raw detection of SWCNT in vivo by susceptibility-weighted MRI.Results: A transitional accumulation in the spleen and liver was observed by MRI. Raman spectroscopy, iron assays, and histological findings confirmed the MRI readouts. Moreover, no acute toxicological effect on the liver metabolic profile was observed using the HR-MAS technique, as confirmed by quantitative real

  17. In vitro evaluation, biodistribution and scintigraphic imaging in mice of radiolabeled anthrax toxins

    International Nuclear Information System (INIS)

    Dadachova, Ekaterina; Rivera, Johanna; Revskaya, Ekaterina; Nakouzi, Antonio; Cahill, Sean M.; Blumenstein, Michael; Xiao, Hui; Rykunov, Dmitry; Casadevall, Arturo

    2008-01-01

    Introduction: There is a lot of interest towards creating therapies and vaccines for Bacillus anthracis, a bacterium which causes anthrax in humans and which spores can be made into potent biological weapons. Systemic injection of lethal factor (LF), edema factor (EF) and protective antigen (PA) in mice produces toxicity, and this protocol is commonly used to investigate the efficacy of specific antibodies in passive protection and vaccine studies. Availability of toxins labeled with imageable radioisotopes would allow to demonstrate their tissue distribution after intravenous injection at toxin concentration that are below pharmacologically significant to avoid masking by toxic effects. Methods: LF, EF and PA were radiolabeled with 188 Re and 99m Tc, and their performance in vitro was evaluated by macrophages and Chinese hamster ovary cells toxicity assays and by binding to macrophages. Scintigraphic imaging and biodistribution of intravenously (IV) injected 99m Tc-and 123 I-labeled toxins was performed in BALB/c mice. Results: Radiolabeled toxins preserved their biological activity. Scatchard-type analysis of the binding of radiolabeled PA to the J774.16 macrophage-like cells revealed 6.6x10 4 binding sites per cell with a dissociation constant of 6.7 nM. Comparative scintigraphic imaging of mice injected intravenously with either 99m Tc-or 123 I-labeled PA, EF and LF toxins demonstrated similar biodistribution patterns with early localization of radioactivity in the liver, spleen, intestines and excretion through kidneys. The finding of renal excretion shortly after IV injection strongly suggests that toxins are rapidly degraded which could contribute to the variability of mouse toxigenic assays. Biodistribution studies confirmed that all three toxins concentrated in the liver and the presence of high levels of radioactivity again implied rapid degradation in vivo. Conclusions: The availability of 188 Re and 99m Tc-labeled PA, LF and EF toxins allowed us to

  18. Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat

    Directory of Open Access Journals (Sweden)

    Barrefelt A

    2013-08-01

    Full Text Available Åsa Barrefelt,1,2,* Maryam Saghafian,2,* Raoul Kuiper,3 Fei Ye,4 Gabriella Egri,5 Moritz Klickermann,5 Torkel B Brismar,1 Peter Aspelin,1 Mamoun Muhammed,4 Lars Dähne,5 Moustapha Hassan2,6 1Department of Clinical Science, Intervention and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, and Department of Radiology, Karolinska University Hospital-Huddinge, Stockholm, Sweden; 2Experimental Cancer Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; 3Karolinska Institute Core Facility for Morphologic Phenotype Analysis, Clinical Research Center, Karolinska University Hospital-Huddinge, Stockholm, Sweden; 4Division of Functional Materials, Department of Materials and Nano Physics, Royal Institute of Technology, Stockholm, Sweden; 5Surflay Nanotec GmbH, Berlin, Germany; 6Clinical Research Center, Karolinska University Hospital-Huddinge, Stockholm, Sweden *These authors contributed equally to this work Background: In the present investigation, we studied the kinetics and biodistribution of a contrast agent consisting of poly(vinyl alcohol (PVA microbubbles containing superparamagnetic iron oxide (SPION trapped between the PVA layers (SPION microbubbles. Methods: The biological fate of SPION microbubbles was determined in Sprague-Dawley rats after intravenous administration. Biodistribution and elimination of the microbubbles were studied in rats using magnetic resonance imaging for a period of 6 weeks. The rats were sacrificed and perfusion-fixated at different time points. The magnetic resonance imaging results obtained were compared with histopathologic findings in different organs. Results: SPION microbubbles could be detected in the liver using magnetic resonance imaging as early as 10 minutes post injection. The maximum signal was detected between 24 hours and one week post injection. Histopathology showed the presence of clustered SPION microbubbles predominantly in the lungs from

  19. The role of cortical and hypothalamic histamine-3 receptors in the modulation of central histamine neurotransmission : an in vivo electrophysiology and microdialysis study

    NARCIS (Netherlands)

    Flik, Gunnar; Dremencov, Eliyahu; Cremers, Thomas I. H. F.; Folgering, Joost H. A.; Westerink, Ben H. C.

    2011-01-01

    The current study aimed to investigate the effect of histamine-3 (H3) receptors, expressed in the tuberomammillary nucleus (TMN) of the hypothalamus and in the prefrontal cortex (PFC), on histamine neurotransmission in the rat brain. The firing activity of histamine neurons in the TMN was measured

  20. Teaching Cardiac Electrophysiology Modeling to Undergraduate Students: Laboratory Exercises and GPU Programming for the Study of Arrhythmias and Spiral Wave Dynamics

    Science.gov (United States)

    Bartocci, Ezio; Singh, Rupinder; von Stein, Frederick B.; Amedome, Avessie; Caceres, Alan Joseph J.; Castillo, Juan; Closser, Evan; Deards, Gabriel; Goltsev, Andriy; Ines, Roumwelle Sta.; Isbilir, Cem; Marc, Joan K.; Moore, Diquan; Pardi, Dana; Sadhu, Sandeep; Sanchez, Samuel; Sharma, Pooja; Singh, Anoopa; Rogers, Joshua; Wolinetz, Aron; Grosso-Applewhite, Terri; Zhao, Kai; Filipski, Andrew B.; Gilmour, Robert F., Jr.; Grosu, Radu; Glimm, James; Smolka, Scott A.; Cherry, Elizabeth M.; Clarke, Edmund M.; Griffeth, Nancy; Fenton, Flavio H.

    2011-01-01

    As part of a 3-wk intersession workshop funded by a National Science Foundation Expeditions in Computing award, 15 undergraduate students from the City University of New York collaborated on a study aimed at characterizing the voltage dynamics and arrhythmogenic behavior of cardiac cells for a broad range of physiologically relevant conditions…

  1. Clinical Characteristics, Electrophysiology, and Skin Biopsy of 38 Peripheral Neuropathy Cases with Small Fiber Involvement of Various Etiologies

    Directory of Open Access Journals (Sweden)

    Bo Sun

    2017-01-01

    Conclusions: IENFD of patients included in the present study weakly correlated with various electrophysiological parameters. Small and large fibers are more involved in patients with MS-related PN than in patients with idiopathic PN.

  2. Inheritance of electrophysiological responses to leaf saps of host- and nonhost plants in two helicoverpa species and their hybrids

    NARCIS (Netherlands)

    Tang, Q.B.; Huang, L.Q.; Wang, C.Z.; Tang, Q.B.T.; Zhan, H.; Loon, van J.J.A.

    2014-01-01

    The polyphagous cotton bollworm Helicoverpa armigera (Hubner) and the oligophagous oriental tobacco budworm Helicoverpa assulta (Guenee) (Lepidoptera: Noctuidae) display contrasting heritable feeding preferences for cotton and pepper leaves. In this study, electrophysiological response patterns to

  3. Synthesis of macrocyclic polyamines; complexation of basic [{sup 99m}TcO{sub 2}{sup +}] and biodistribution of complexed forms; Synthese de polyamines macrocycliques. Complexation du coeur [{sup 99m}TcO{sub 2}{sup +}] et biodistribution des complexes formes

    Energy Technology Data Exchange (ETDEWEB)

    Riche, F.; Vidal, M. [Universite Joseph Fourier, 38 - Grenoble (France); Mathieu, J.P.; Fagret, D.; Comet, M. [Universite Joseph Fourier, 38 - La Tronche (France). Faculte de Medecine; Pasqualini, R. [CIS bio international, 91 - Gif-sur-Yvette (France)

    1996-01-01

    The synthesis of macrocyclic polyamines is described, as well as their complexation with technetium via pertechnetole ligands. Several pertechnetole reducing agents were studied, as well as their method of complexation with polyamines and their charge and lipophilicity. Their biodistribution in the mouse and the dog has been studied by scintiscanning which provides evidence of their excellence as hepatobiliary tracers. (UK).

  4. Biodistribution and radiation dosimetry of [11C]DASB in baboons

    International Nuclear Information System (INIS)

    Belanger, Marie-Jose; Simpson, Norman R.; Wang, Theodore

    2004-01-01

    Objective: The serotonin transporter has been implicated in a variety of conditions including mood disorders and suicidal behavior. In vivo human brain studies with positron emission tomography and the serotonin transporter antagonist [ 11 C]DASB ([ 11 C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile) are ongoing in several laboratories with the maximum administered activity based on dosimetry collected in rodents. We report on the biodistribution and dosimetry of [ 11 C]DASB in the baboon as this species may be a more reliable surrogate for human dosimetry. Methods: Four baboon studies (two studies in each of two baboons) were acquired in an ECAT ACCEL camera after the bolus injection of 183±5 MBq/2.3±1.0 nmol of [ 11 C]DASB. For each study, six whole-body emission scans were collected in 3D mode over 6/7 bed positions for 2 h. Regions of interest were drawn on brain, lungs, liver, gallbladder, spleen, kidneys, small intestine and bladder. Since no fluid was removed from the animal, total body radioactivity was calculated using the injected dose calibrated to the ACCEL image units. Results: Uptake was greatest in lungs, followed by the urinary bladder, gallbladder, brain and other organs. The ligand was eliminated via the hepato-billiary and renal systems. The largest absorbed dose was found in the lungs (3.6x10 -2 mSv/MBq). The absorbed radiation doses in lungs and gallbladder were four and nine times larger than that previously estimated from rat studies. Conclusion: Based on our baboon biodistribution and dose estimates, the lungs are the critical organs for administration of [ 11 C]DASB. In the United States, the absorbed dose to the lungs would limit [ 11 C]DASB administered with the approval of a Radioactive Drug Research Committee to 1400 MBq (37 mCi) in the adult male and 1100 MBq (30 mCi) in the adult female

  5. Effects of Ascorbic Acid on the Amplitude of Ventral Tegmental Area Field Action Potential in Morphine-Exposed Rats (An Electrophysiology Study

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    K Saadipour

    2010-07-01

    Full Text Available Introduction & Objective: Evidences have indicated that the Ventral Tegmental Area (VTA is the major source of dopamine (DA neurons projecting to cortical and limbic regions involved in cognitive and motivational aspects of addiction. Also, studies have indicated that the Ascorbic acid (vitamin C can reduce the dependency symptoms of opioids such as morphine via effect of activity on dopaminergic neuron in VTA. For this reason, the aim of this study was to assess the effects of ascorbic acid on the amplitude of Ventral Tegmental Area field action potential in morphine-exposed rats. Materials & Methods: Forty male Wistar’s rats were used in this experimental study conducted at Yasuj University of Medical Sciences in 2010. Animals were randomly divided into four groups after electrode implantation and recovery period: 1. No- Vit C and No-Addicted group (nVitC.nA 2. Vit C and No-Addicted group (VitC.nA 3. No- Vit C and Addicted group (nVitCA 4.Vit C and Addicted (VitC.A, The Vit C groups received 500 mg/kg of Vit C during 20 days. For addicted groups morphine was administrated once daily for 20 days. In the 20th day, the field potential recording was accomplished. Two-way ANOVA was used for data analysis followed by the Tukey test for post hoc analysis. Results were considered significant at P < 0.05. Results: This study shows the exposure to morphine declined the power of Delta and Beta bands (p<0.05 and Vit C solely enhance power of Theta and Beta (p<0.05, p<0.001 in VTA nuclei. Furthermore, Vit C could alter power of some bands which were affected by morphine. Therefore it seems that Vit C has an increasing effects on them (p<0.05. Conclusion: Although the effect of Vit C on power of the VTA bands is not well known, but it is supposed that this phenomenon can be related to alteration in activity of dopaminergic neuron in the brain.

  6. Electrophysiological and biochemical studies of the effects of radiation on brain activity and development. Progress report, November 1973--October 31, 1974

    International Nuclear Information System (INIS)

    Timiras, P.S.

    1974-01-01

    Some biochemical aspects of synaptogenesis were explored in recent studies, through the use of x-radiation techniques, particularly in the cerebellum where x-radiation was shown to preferentially destroy specific cell populations (the external granular layer cells) as well as to inhibit cell migration. Studies in this area demonstrated clearly that x radiation causes significant abnormalities in cholinergic neurotransmission, in GABA, and in monoamine metabolism. These abnormalities were localized to CNS regions, such as the cerebellum, which were active in terms of cell proliferation, cell migration, and growth at the time of exposure to x-irradiation. The data accumulated thus far does not yet allow conclusions to be drawn as to the mode of action whereby x radiation brings about the increase in cholinergic and monaminergic metabolism; however, it is proposed that x radiation interferes with developmental aspects of neurotransmitter metabolism involving, perhaps, alterations to the cell population of the receptor area and/or changes in the branching of axonal terminals of the particular transmitter neuron. It was further hypothesized that when abnormalities occur in the physical contact of neurons, at critical developmental stages of the nervous system, biochemical aspects of cell differentiation related to neurotransmission are concomitantly affected. Different fibers exert influence on developing neurons and, consequently, that cell connectivity is integrally related to neuronal maturation. (U.S.)

  7. Pharmacokinetics and biodistribution of 11C-HupA in the normal animal

    International Nuclear Information System (INIS)

    Yan Jin; Guan Yihui; Xue Fangping; Zhang Zhenwen; Liu Ping; Lin Yiangtong

    2009-01-01

    Objective: Hula is one of the potential drugs which can be used to treat Alzheimer's disease (Ad). The aim of this study was to explore the pharmacokinetics and biodistribution of Hula in vivo by using 11 C-Hula. Methods: A total of 25 Sd rats were studied. They were divided into 5 groups (5 rats in each group). All had intravenous injection of 22 MBq (in 0.2 ml) 11 C-Hula through tail vein. Dynamic imaging Was acquired from 5 to 90 minutes after injection. Venous blood and organ activities were collected at 5, 15, 30, 60. and 90 minutes after injection. Percentage activity of injected dose per gram of tissue (%ID/g) was calculated to characterize the biodistribution of tracer in different brain regions: frontal,apical, temporal, occipital, cerebellum, hippocampus, striatum, thalamencephalon, and brain stem, Variance analysis using SPSS 11.5 software was performed and compared among the study groups. Results: 11 C-HupA was characteristic for its quick clearance from blood, with half time T 1/2 of (14.61 ± 1.77) min, and clearance rate (CL) of (0.12 ± 0.01) ml · min -1 · kg -1 . Metabolism was through liver, and excretion through kidney. Pharmacokinetics of 11 C-HupA in rats corresponded to a one-compartment model. with an activity curve (area under curve, AUC) 0-8 integral of (167.57 ± 12.39) ml · min -1 · kg -1 . There was significant difference of 11 C-HupA distribution in different brain regions, being greater in cerebral cortex, hippocampus, hypothalamus and brain stem. Conclusions: Pharmacokinetic study of 11 C-HupA in brain was fast. convenient and showed high specificity and sensitivity. Its ability to quantitatively evaluate brain function and its characteristic distribution in mice provided some evidence for monitoring therapy in AD patients. (authors)

  8. Assessing the permeability of the rat sciatic nerve epineural sheath against compounds with local anesthetic activity: an ex vivo electrophysiological study.

    Science.gov (United States)

    Kagiava, Alexia; Theophilidis, George

    2013-10-01

    Abstract Studies have shown that the sciatic nerve epineural sheath acts as a barrier and has a delaying effect on the diffusion of local anesthetics into the nerve fibers and endoneurium. The purpose of this work is to assess and to quantify the permeability of the epineural sheath. For this purpose, we isolated the rat sciatic nerve in a three-chamber recording bath that allowed us to monitor the constant in amplitude evoked nerve compound action potential (nCAP) for over 24 h. For nerves exposed to the compounds under investigation, we estimated the IT50 the time required to inhibit the nCAP to 50% of its initial value. For desheathed nerves, the half-vitality time was denoted as IT50(-) and for the ensheath normal nerves as IT50(+). There was no significant difference between the IT50 of desheathed and ensheathed nerves exposed to normal saline. The IT50(-) for nerves exposed to 40 mM lidocaine was 12.1 ± 0.95 s (n=14) and the IT50(+) was 341.4 ± 2.49 s (n=6). The permeability (P) coefficient of the epineural sheath was defined as the ratio IT50(+)/IT50(-). The P coefficient for 40 mM lidocaine and linalool was 28.2 and 3.48, correspondingly, and for 30 mM 2-heptanone was 4.87. This is an indication that the epineural sheath provided a stronger barrier against lidocaine, compared to natural local anesthetics, linalool and 2-heptanone. The methodology presented here is a useful tool for studying epineural sheath permeability to compounds with local anesthetic properties.

  9. Effects of Cornus mas L. and Morus rubra L. extracts on penicillin-induced epileptiform activity: an electrophysiological and biochemical study.

    Science.gov (United States)

    Tubaş, Filiz; Per, Sedat; Taşdemir, Abdulkadir; Bayram, Ayşe Kaçar; Yıldırım, Mehmet; Uzun, Aydın; Saraymen, Recep; Gümüş, Hakan; Elmalı, Ferhan; Per, Hüseyin

    2017-01-01

    Traditionally, Morus rubra L. (Moraceae) (red mulberry) and Cornus mas L. (Cornacea) (cornelian cherry) fruits are eaten fresh and are also used in marmalades, juices, jam, natural dyes in Turkey and are believed to have beneficial effects in case of multiple health issues such as antipyretic, diarrhea and intestinal parasites. However, the effects of M. rubra and C. mas on epilepsy has not been known. This study evaluates the effects of M. rubra and C. mas extracts on penicillin-induced epileptiform activity. Sixty Wistar rats randomly divided into ten groups (n=6): control, sham, penicillin, penicillin+M. rubra extract (2.5, 5, 10, 20 mg/kg) and penicillin+C. mas extract (2.5, 5, 10 mg/kg). Epileptiform activity was induced by using penicillin (500 IU, i.c.) and electrocorticogram records (150 min) were obtained. Also, biochemical analysis in blood samples were evaluated. According to the electrocorticogram analysis, the effective dose was detected as 10 mg/kg for both C. mas and M. rubra. This dose decreased the spike frequencies of convulsions while amplitude wasn't changed by both substances. In erythrocyte studies, there were significant differences regarding nitric oxide in the control, sham and penicillin groups. There were significant differences regarding malondialdehyde in all groups. In the plasma, there were significant differences among groups regarding xanthine oxidase in the penicillin‑C. mas and penicillin‑M. rubra groups. There were differences regarding malondialdehyde in the penicillin-C. mas and M. rubra-C. mas groups. Both extracts reduced the frequency of epileptiform activity. After administration of the extracts malondialdehyde levels decreased also in both erythrocytes and plasma.

  10. Linking Theoretical Decision-making Mechanisms in the Simon Task with Electrophysiological Data: A Model-based Neuroscience Study in Humans.

    Science.gov (United States)

    Servant, Mathieu; White, Corey; Montagnini, Anna; Burle, Borís

    2016-10-01

    A current challenge for decision-making research is in extending models of simple decisions to more complex and ecological choice situations. Conflict tasks (e.g., Simon, Stroop, Eriksen flanker) have been the focus of much interest, because they provide a decision-making context representative of everyday life experiences. Modeling efforts have led to an elaborated drift diffusion model for conflict tasks (DMC), which implements a superimposition of automatic and controlled decision activations. The DMC has proven to