Resin hemoperfusion in dogs intoxicated with ethchlorvynol (Placidyl®)

Resin hemoperfusion in dogs intoxicated with ethchlorvynol (Placidyl®). Kinetic parameters were studied to determine the effectiveness of hemoperfusion in removing ethchlorvynol from the plasma and red blood cells (RBC) of intoxicated dogs. Perfusion columns contained polystyrene/divinyl benzene resin (XAD-4 Amberlite(®)). Column clearances of ethchlorvynol averaged 96.5 ± 0.4% of the plasma flow rate (mean ±SEM, 9 dogs). Plasma ethchlorvynol t1/2's during preperfusion periods averaged 94.1hr. During hemoperfusion, t1/2's averaged 3.8hr, or 90.3hr shorter than at the endogenous rate of detoxication. There was no significant difference between preperfusion and postperfusion half lives. An estimate based on plasma column clearance suggests that 1.5 ± 0.1g ethchlorvynol, or 19.0 ± 2.8% of the dose, was removed by hemoperfusion. The amount eluted from the resin was 2.9 ± 0.3g (37.2 ± 5.8% of the dose), or about twice the amount apparent from plasma clearance alone. Further, the volume of distribution of ethchlorvynol was 2.3 ± 0.2 liters/kg, suggesting significant distribution to intracellular and extravascular compartments. The results show that resin hemoperfusion removes a large fraction of ethchlorvynol from intoxicated dogs, and greatly adds to endogenous mechanisms for elimination. Ethchlorvynol was removed from RBC directly, and ultimately from extravascular sites as well.Hémoperfusion sur résine chez des chiens intoxiqués par l'éthchlorvynol (Placidyl®). Afin de déterminer l'efficacité de l'hémoperfusion dans la soustraction d'éthchlorvynol du plasma et des hématies de chiens intoxiqués, les paramètres cinétiques ont été mesurés. Les colonnes de perfusion contenaient une résine polystyrène/divinyl benzène (XAD-4 Amberlite®). La clearance de l'éthchlorvynol par les colonnes était en moyenne de 96,5 ± 0,4% du débit plasmatique (moyenne ±SEM, 9 chiens). La plasmatique de l'éthchlorvynol t½'s pendant la période préalable à la perfusion était de 94,1 heures. Pendant l'hémoperfusion, t½'s était en moyenne de 3,8 heures, soit 90,3 heures de moins qu'au cours de la détoxication spontanée. Il n'a pas été observé de différence entre les demi vies avant et après perfusion. Une estimation fondée sur la clearance des colonnes suggère que 1,5 ± 0,1g d'éthchlorvynol, soit 19,0 ± 2,8% de la dose a été soustrait par l'hémoperfusion. La quantité éluée de la résine a été de 2,9 ± 0,3g (37,2 ± 5,8% de la dose), soit le double de la quantité évaluée à partir de la clearance du plasma. De plus, le volume de distribution de l'éthchlorvynol était de 2,3 ± 0,2 litres/kg, ce qui suggère une distribution importante dans les compartiments intracellulaire et extravasculaire. Les résultats montrent que l'hémoperfusion sur résine soustrait une fraction importante de l'éthchlorvynol chez des chiens intoxiqués et ajoute une élimination importante aux mécanismes endogènes. L'ethchlorvynol a été soustrait des hématies directement et finalement des sites extravasculaires aussi

Foolproof quick-release locking pin

Locking pin can be withdrawn only when stress on the joint is negligible. Pin consists of a forward-pointing sleeve, a spring-loaded sliding handle, and a sliding plunger. Plunger movement controls installation and withdrawal of pin

Solar Protons and Magnetic Storms in July 1961

Injun i satellite observations of solar protons and magnetic storm

An evaluation of geomagnetic harmonic series for 1100 kilometers altitude

Geomagnetic harmonic series evaluation for 1100 kilometers altitude using satellite observation

The scaler magnetic intensity at 1100 kilometers in middle and low latitudes

Satellite borne magnetometer for measuring scalar magnetic intensities in middle and low latitudes at 1100 km altitud

A Method for Murine Islet Isolation and Subcapsular Kidney Transplantation

Since the early pioneering work of Ballinger and Reckard demonstrating that transplantation of islets of Langerhans into diabetic rodents could normalize their blood glucose levels, islet transplantation has been proposed to be a potential treatment for type 1 diabetes 1,2. More recently, advances in human islet transplantation have further strengthened this view 1,3. However, two major limitations prevent islet transplantation from being a widespread clinical reality: (a) the requirement for large numbers of islets per patient, which severely reduces the number of potential recipients, and (b) the need for heavy immunosuppression, which significantly affects the pediatric population of patients due to their vulnerability to long-term immunosuppression. Strategies that can overcome these limitations have the potential to enhance the therapeutic utility of islet transplantation

A novel 18F-labelled high affinity agent for PET imaging of the translocator protein

The translocator protein (TSPO) is an important target for imaging focal neuroinflammation in diseases such as brain cancer, stroke and neurodegeneration, but current tracers for non-invasive imaging of TSPO have important limitations. We present the synthesis and evaluation of a novel 3-fluoromethylquinoline-2-carboxamide, AB5186, which was prepared in eight steps using a one-pot two component indium(III)-catalysed reaction for the rapid and efficient assembly of the 4-phenylquinoline core. Biological assessment and the implementation of a physicochemical study showed AB5186 to have low nanomolar affinity for TSPO, as well as optimal plasma protein binding and membrane permeability properties. Generation of [18F]-AB5186 through 18F incorporation was achieved in good radiochemical yield and subsequent in vitro and ex vivo autoradiography revealed the ability of this compound to bind with specificity to TSPO in mouse glioblastoma xenografts. Initial positron emission tomography imaging of a glioma bearing mouse and a healthy baboon support the potential for [18F]-AB5186 use as a radiotracer for non-invasive TSPO imaging in vivo

Synthesis and evaluation of a radioiodinated tracer with specificity for poly(ADP-ribose) polymerase-1 (PARP-1) in vivo

Interest in nuclear imaging of poly(ADP-ribose) polymerase-1 (PARP-1) has grown in recent years due to the ability of PARP-1 to act as a biomarker for glioblastoma and increased clinical use of PARP-1 inhibitors. This study reports the identification of a lead iodinated analog 5 of the clinical PARP-1 inhibitor olaparib as a potential single-photon emission computed tomography (SPECT) imaging agent. Compound 5 was shown to be a potent PARP-1 inhibitor in cell-free and cellular assays, and it exhibited mouse plasma stability but approximately 3-fold greater intrinsic clearance when compared to olaparib. An (123)I-labeled version of 5 was generated using solid state halogen exchange methodology. Ex vivo biodistribution studies of [(123)I]-5 in mice bearing subcutaneous glioblastoma xenografts revealed that the tracer had the ability to be retained in tumour tissue and bind to PARP-1 with specificity. These findings support further investigations of [(123)I]-5 as a non-invasive PARP-1 SPECT imaging agent

Theoretical Study of the Effect of Ionospheric Return Currents on the Electron Temperature

An electron heat flow can occur in a partially ionized plasma in response to either an electron temperature gradient (thermal conduction) or an electron current (thermoelectric heat flow). The former process has been extensively studied, while the latter process has received relatively little attention. Therefore a time-dependent three-dimensional model of the high-latitude ionosphere was used to study the effect of field-aligned ionospheric return currents on auroral electron temperatures for different seasonal and solar cycle conditions as well as for different upper boundary heat fluxes. The results of this study lead to the following conclusions: (1) The average, large-scale, return current densities, which are a few microamps per square meter, are too small to affect auroral electron temperatures. (2) Current densities greater than about 10−5 A m−2 are needed for thermoelectric heat flow to be important. (3) The thermoelectric effect displays a marked solar cycle and seasonal dependence. (4) Thermoelectric heat transport corresponds to an upward flow of electron energy. (5) This energy flow can be either a source or sink of electron energy, depending on the altitude and geophysical conditions. (6) Thermoelectric heat transport is typically a sink above 300 km and acts to lower ambient electron temperatures by as much as 2000 K for field-aligned return current densities of the order of 5 × 10−5 A m−2. For this case, the electron temperature decreases with altitude above 300 km with a gradient that can exceed 1 K km−1. Also, the electron temperature can drop below both the ion and neutral temperatures in the upper F region owing to thermoelectric cooling. (7) A downward magnetospheric heat flux in combinations with an upward thermoelectric heat flux can produce steep positive electron temperature gradients in the topside ionosphere