A fiber based in vitro optical signal diagnosis technique for interspecies transmissibility

Author(s):  
Hyun Jin Bang ◽  
Seung Rag Lee ◽  
Byungyeon Kim ◽  
Kiri Lee ◽  
Minsuk Lee ◽  
...  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Zsigmond Benkő ◽  
Kinga Moldován ◽  
Katalin Szádeczky-Kardoss ◽  
László Zalányi ◽  
Sándor Borbély ◽  
...  

1999 ◽  
Vol 11 (6) ◽  
pp. 1877-1882 ◽  
Author(s):  
Katharina Buchheim ◽  
Sebastian Schuchmann ◽  
Herbert Siegmund ◽  
Hans Jürgen Gabriel ◽  
Uwe Heinemann ◽  
...  

1980 ◽  
Vol 239 (3) ◽  
pp. R326-R331
Author(s):  
S. A. Halbert ◽  
R. J. Bourdage ◽  
J. L. Boling ◽  
J. A. Ringo ◽  
R. J. Blandau

An optoelectronic instrument to record oviductal muscular activity in chronically instrumented animals was evaluated in in vitro and in vivo experiments. The intensity of red light transmitted through the oviduct was modulated by contractions of the oviductal wall producing an optical analog of the mechanical events. Accuracy of the analog was tested by Fourier analysis of signals from mechanical and optoelectronic transducers placed at the same site on the oviduct; the results validated the use of the optical device as a contraction event sensor. Contractions of the tubal mesenteries had less effect on the optical signal than on signals from extraluminal mechanical transducers. Optical and photographic recordings of luminal transport in exposed oviducts showed a correspondence of intraluminal movements to events in the optical contraction signal. This instrument does not alter tubal function, and thus it is an especially useful experimental tool to investigate the role of oviductal muscular activity in fertility.


1990 ◽  
Vol 64 (6) ◽  
pp. 1767-1790 ◽  
Author(s):  
A. R. Cinelli ◽  
B. M. Salzberg

1. Multiple site optical recording of transmembrane voltage (MSORTV), together with conventional extracellular electrophysiological techniques were utilized with in vivo and in vitro preparations of the olfactory bulb of the Atlantic skate Raja erinacea to analyze electrical activity simultaneously in layers deep to the glomerular layer. 2. In the living animals and the in vitro isolated olfactory bulb, orthodromic stimulation evoked a compound action potential in the olfactory nerve fibers, followed by a series of early field-potential waves (N1, P1, N2, P2, N3, and N4). During paired stimulation experiments, unusual patterns of facilitation and suppression were observed for the N2 wave. 3. After orthodromic stimulation, single units, presumably mitral/tufted cells, exhibited a period of early discharge, followed by a period of suppression of spontaneous activity and of their test response in a pair stimulation paradigm. Some neurons also exhibited a labile period of reexcitation that was accompanied by a late surface negative field potential; these responses were also present in olfactory bulb slices. 4. Extrinsic absorption changes obtained from 500-microns saggital slices of the olfactory bulb, stained with the pyrazooxonal dye RH-155, consisted mainly of two types of depolarizing responses, a fast and a slow component, followed under some conditions by a late hyperpolarization. All signals exhibited wavelength dependences typical of the action spectrum of RH-155 and were abolished in the presence of tetrodotoxin (TTX) or high K+ in the bath. 5. The fast component of the optical signal represents synchronous compound action potentials conducted by the olfactory nerve fibers or evoked in the mitral/tufted somata and axonal pathways. The slow depolarizing optical signal appeared, after orthodromic stimuli, mainly in the zone between the glomeruli and the mitral/tufted layer; barium (1–10 mM), which depolarizes glial cells, increased its size and duration, suggesting that this signal does not reflect a glial response to [K+]o. 6. Different condition/test (C/T) intervals produced partial or complete suppression of the test response, depending on the recording site and the stimulus intensity. Just threshold orthodromic stimuli evoked an intermediate period of facilitation of the slow signals. A similar period was also observed in the N2 wave of the field potential. 7. Calcium channel blockers such as cadmium ion, or a low Ca2+ medium, suppressed the slow optical component whether evoked by orthodromic, antidromic, or direct stimulation. gamma-Aminobutyric acid (GABA) and baclofen also reduced or blocked the slow component of the extrinsic absorption signal.(ABSTRACT TRUNCATED AT 400 WORDS)


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thomas H. Craven ◽  
Tashfeen Walton ◽  
Ahsan R. Akram ◽  
Emma Scholefield ◽  
Neil McDonald ◽  
...  

AbstractNeutrophil activation is an integral process to acute inflammation and is associated with adverse clinical sequelae. Identification of neutrophil activation in real time in the lungs of patients may permit biological stratification of patients in otherwise heterogenous cohorts typically defined by clinical criteria. No methods for identifying neutrophil activation in real time in the lungs of patients currently exist. We developed a bespoke molecular imaging probe targeting three characteristic signatures of neutrophil activation: pinocytosis, phagosomal alkalinisation, and human neutrophil elastase (HNE) activity. The probe functioned as designed in vitro and ex vivo. We evaluated optical endomicroscopy imaging of neutrophil activity using the probe in real-time at the bedside of healthy volunteers, patients with bronchiectasis, and critically unwell mechanically ventilated patients. We detected a range of imaging responses in vivo reflecting heterogeneity of condition and severity. We corroborated optical signal was due to probe function and neutrophil activation.


2021 ◽  
Vol 15 ◽  
Author(s):  
Yi-Ling Lu ◽  
Helen E. Scharfman

Spreading depolarization (SD) is a sudden, large, and synchronous depolarization of principal cells which also involves interneurons and astrocytes. It is followed by depression of neuronal activity, and it slowly propagates across brain regions like cortex or hippocampus. SD is considered to be mechanistically relevant to migraine, epilepsy, and traumatic brain injury (TBI), but there are many questions about its basic neurophysiology and spread. Research into SD in hippocampus using slices is often used to gain insight and SD is usually triggered by a focal stimulus with or without an altered extracellular buffer. Here, we optimize an in vitro experimental model allowing us to record SD without focal stimulation, which we call spontaneous. This method uses only an altered extracellular buffer containing 0 mM Mg2+ and 5 mM K+ and makes it possible for simultaneous patch and extracellular recording in a submerged chamber plus intrinsic optical imaging in slices of either sex. We also add methods for quantification and show the quantified optical signal is much more complex than imaging alone would suggest. In brief, acute hippocampal slices were prepared with a chamber holding a submerged slice but with flow of artificial cerebrospinal fluid (aCSF) above and below, which we call interface-like. As soon as slices were placed in the chamber, aCSF with 0 Mg2+/5 K+ was used. Most mouse slices developed SD and did so in the first hour of 0 Mg2+/5 K+ aCSF exposure. In addition, prolonged bursts we call seizure-like events (SLEs) occurred, and the interactions between SD and SLEs suggest potentially important relationships. Differences between rats and mice in different chambers are described. Regarding optical imaging, SD originated in CA3 and the pattern of spread to CA1 and the dentate gyrus was similar in some ways to prior studies but also showed interesting differences. In summary, the methods are easy to use, provide new opportunities to study SD, new insights, and are inexpensive. They support previous suggestions that SD is diverse, and also suggest that participation by the dentate gyrus merits greater attention.


2009 ◽  
Vol 58 (6) ◽  
Author(s):  
Justo Aznar

Il termine “designer baby” può essere usato per riferirsi ad una serie di tecniche incluse quelle di selezione del sesso per evitare la nascita di bambini con malattie legate al cromosoma sessuale X, la diagnosi genetica preimpiantatoria per selezionare gli embrioni non affetti da disordini genetici, e il potenziamento di caratteristiche come l’intelligenza, le abilità sportive e la bellezza. La produzione di “designer babies” comporta problemi medici ed etici. In questo articolo passiamo in rassegna in particolar modo i secondi. Secondo la nostra opinione, gli aspetti più interessanti sono: 1. la strumentalizzazione dei bambini prodotti; 2. le possibilità che queste tecniche possono aprire le porte ad altre eticamente non adeguate; 3. il possibile beneficio dei genitori; 4. l’impossibilità di ottenere il consenso dei bambini; 5. i problemi clinici che l’utilizzazione della diagnosi genetica preimplantatoria può produrre; 6. quelli della fecondazione in vitro; 7. il grande numero di embrioni che vengono distrutti a seguito dell’uso di queste tecniche; 8. infine l’esistenza o meno di alternative mediche per la produzione dei “designer babies”. Il nostro parere è che uno dei problemi etici più importanti è rappresentato dal gran numero di embrioni che si perdono nella produzione dei “designer babies”. Nel caso di Adam Nash si usarono, infatti, 33 embrioni per produrre un solo bambino, con un’efficienza del 3%. In uno studio nel quale sono stati valutati i dati delle principali cliniche di medicina riproduttiva del mondo emerge che sono stati utilizzati 1130 embrioni per far nascere 35 bambini, con un’efficienza dell’1,15%. ---------- The term “designer babies” may be used to refer to a range of reproductive techniques including the use of sex selection techniques to prevent the birth of children with X-linked diseases, preimplantation genetic diagnosis to select for embryos free from genetic disorders, selection techniques for eggs, sperm or embryo donors with particular characteristics, and the enhancement of features such as intelligence, sporting ability or attractiveness. The production of designer babies entails specific medical and ethical problems. In this article, we will essentially address the latter. In our opinion, the most important aspects to consider in an ethical reflection on the production of designer babies are: 1. the instrumentalisation of the child produced in such a way that these children would be treated as commodities; 2. the secondary consequences that could result from the legal authorisation of this technique could open the door to other ethically unsuitable techniques, especially sex selection, 3. the benefit that the parents may obtain; 4. the impossibility of obtaining the consent of the child him/herself; 5. the medical problems that the use of the preimplantational genetic diagnosis technique may cause in the embryo generated; 6. as well as those inherent in the in-vitro fertilisation technique; 7. the negative ethical burden involved in the high number of embryos lost with this practice, i.e. the high number of human lives destroyed; 8. and finally, whether or not a medical alternative to the production of designer babies exists, since if so, their generation would be doubly unjustified. We think that one of the most important ethical problems is the high number of embryos lost in the production of designer babies. Thus, it can be verified that in the case of the first designer baby, Adam Nash, 33 embryos were used to obtain a useful child, so the efficiency was approximately 3%. In a study which collected the joint data from some of the leading reproductive medicine clinics in the world in which designer babies are produced, is showed that from 1130 embryos, only 35 designer babies were obtained, which indicates that the efficiency of production of these children was 1.15%.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1674-1674 ◽  
Author(s):  
Paul W. Manley ◽  
Sandra W. Cowan-Jacob ◽  
Gabriele Fendrich ◽  
Wolfgang Jahnke ◽  
Doriano Fabbro

Abstract Abstract 1674 Background: Imatinib, nilotinib and dasatinib are effective therapies for chronic myeloid leukemia, as a consequence of their inhibiting the Abelson tyrosine kinase activity of the BCR-ABL oncoprotein. Their rank-order of potency in assays assessing either effects on BCR-ABL autophosphorylation or cell proliferation is dasatinib > nilotinib > imatinib. However, such quantitative in vitro differences do not directly translate into pharmacological differences due to other factors (Laneuville et al. JCO 2010;28: e169), such as pharmacokinetics (dasatinib, nilotinib and imatinib have plasma half-lives in CML patients of 3–5, 19±6 and ≈20 hours respectively) and pharmacodynamics, including cell penetration and protein binding. Here we report the ABL binding kinetics for these drugs and discuss how the data can be related to target occupancy and the pharmacodynamic properties of the drugs. Methods: Active phosphorylated ABL (residues 118–535 of SH1 domain) was purified from insect cells and was treated with shrimp alkaline phosphatase to afford the dephosphorylated form. Drug binding kinetics were studied using the Proteros reporter displacement assay. This utilises reporter probes that bind to the target protein, with the proximity between reporter and protein resulting in the emission of an optical signal, so that compounds which bind to the same site as the reporter probe displace the probe, causing signal diminution. The rate of reporter displacement is measured over time after addition of compounds at various concentrations. Results and Conclusions: The kinetic parameters for the interaction between the drugs and either phosphorylated or dephosporylated ABL are tabulated below. The binding affinity (KD) is related to the association rate constant (kon) and the dissociation rate constant (koff) by KD = koff / kon. The kon rates (dasatinib > imatinib > nilotinib) reflect that dasatinib recognises the phosphorylated, catalytically-active resting-state conformation of ABL (DGF-in; Tokarski et al. Cancer Res 2006;66: 5790 and Vajpai et al. JBC 2008;283: 18292), whereas the other drugs bind to an inactive conformation (DFG-out) and this leads to dasatinib having the highest KD of the three drugs. However, in terms of their Koff rates, the rank order of activity is reversed, reflecting the strong binding of nilotinib to the DFG-out conformation and the thermodynamic stability of the ABL-nilotinib complex. The stability of the complexes between the drugs and ABL protein is quantifiable through the half-life of the complexes (residence times) and for nilotinib is over 3 hours. It is generally recognised that prolonged residence-times for drugs bound to their pharmacologically-relevant protein target, can uncouple pharmacodynamic target inhibition from tissue level pharmacokinetics. Furthermore, high off-rate selectivity can minimise the side-effects of drugs caused by off-target binding, which is reduced in the case of drugs with high target residence times. Thus this kinetic analysis can provide an explanation for the high efficacy of nilotinib in CML patients, at doses that cause relatively few side-effects. Disclosures: Manley: Novartis Pharma AG: Employment. Cowan-Jacob:Novartis Pharma AG: Employment. Fendrich:Novartis Pharma AG: Employment. Jahnke:Novartis Pharma AG: Employment. Fabbro:Novartis Pharma AG: Employment.


2021 ◽  
Vol 17 ◽  
Author(s):  
Mingmin Li ◽  
Changhua An ◽  
Tie Wang

Background: Integrating metal-organic frameworks (MOFs) with other functional materials to form MOF-composites has attracted great attention. Their diverse and synergetic performance (e.g., mechanical stability, conductivity, optical signal and catalytic activity) facilitates their applications in sensing of various target molecules. Methods: Up to now, a wide range of MOF-composites have been designed and synthesized. The choice of appropriate parent materials, as well as their combination strategy, is of great importance for their performance. Prior to the design of MOF-composites for certain sensing applications, it is necessary to evaluate the advantages of the composites compared to the pristine MOFs and other functional materials. Results: In this review, an overview of the significant advances in the development of diverse MOF-composites was presented, with special emphases on the synergistic effects in sensing (e.g., optical, electrochemical and biological) applications of the composites. Additionally, the challenges and future prospective of MOF-composites as an innovative sensing platform were discussed to seek for further development in this emerging research area. Conclusion: MOF-composites show great potential in sensing applications. Further efforts are still urgent to advance their applications in point-of-care (POC) detection and in vitro diagnosis (IVD).


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