Opioid growth factor modulates angiogenesis

AbstractObjective: Induced angiogenesis has recently been attempted as a therapeutic modality in patients with occlusive arterial atherosclerotic disease. We investigated the possible role of endogenous opioids in the modulation of angiogenesis. Methods: Chick chorioallantoic membrane was used as an in vivo model to study angiogenesis. Fertilized chick eggs were incubated for 3 days, explanted, and incubated for an additional 2 days. Three-millimeter methylcellulose disks were placed on the surface of the chorioallantoic membrane; each disk contained opioid growth factor ([Met5]-enkephalin; 5 μg), the short-acting opioid receptor antagonist naloxone (5 μg), opioid growth factor and naloxone together (5 μg of each), the long-acting opioid antagonist naltrexone (5 μg), or distilled water (control). A second series of experiments was performed with distilled water, the angiogenic inhibitor retinoic acid (1 μg), and vascular endothelial growth factor (1 μg) to further evaluate our model. The developing vasculature was imaged 2 days later with a digital camera and exported to a computer for image analysis. Total number of blood vessels, total vessel length, and mean vessel length were measured within a 100-mm2 region surrounding each applied disk. Immunocytochemical analysis was performed with antibodies directed against opioid growth factor and its receptor (OGFr). Results: Opioid growth factor had a significant inhibitory effect on angiogenesis, both the number of blood vessels and the total vessel length being decreased (by 35% and 20%, respectively) in comparison with control levels (P <.005). The simultaneous addition of naloxone and opioid growth factor had no effect on blood vessel growth, nor did naloxone alone. Chorioallantoic membranes exposed to naltrexone displayed increases of 51% and 24% in blood vessel number and length, respectively, in comparison with control specimens (P <.005). These results indicate that the opioid growth factor effects are receptor mediated and tonically active. Immunocytochemistry demonstrated the presence of both opioid growth factor and OGFr within the endothelial cells and mesenchymal cells of the developing chorioallantoic membrane vessel wall. Retinoic acid significantly reduced the number and the total length of blood vessels, whereas vascular endothelial growth factor increased both the number and the length of blood vessels in comparison with the controls (P <.0001). The magnitude of opioid growth factor's effects were comparable to those seen with retinoic acid, whereas inhibition of opioid growth factor with naltrexone induced an increase in total vessel length comparable to that for vascular endothelial growth factor. Conclusions: These results demonstrate for the first time that endogenous opioids modulate in vivo angiogenesis. Opioid growth factor is a tonically active peptide that has a receptor-mediated action in regulating angiogenesis in developing endothelial and mesenchymal vascular cells. (J Vasc Surg 2000;32:364-73.

The LBNO long-baseline oscillation sensitivities with two conventional neutrino beams at different baselines

The proposed Long Baseline Neutrino Observatory (LBNO) initially consists of $\sim 20$ kton liquid double phase TPC complemented by a magnetised iron calorimeter, to be installed at the Pyh\"asalmi mine, at a distance of 2300 km from CERN. The conventional neutrino beam is produced by 400 GeV protons accelerated at the SPS accelerator delivering 700 kW of power. The long baseline provides a unique opportunity to study neutrino flavour oscillations over their 1st and 2nd oscillation maxima exploring the $L/E$ behaviour, and distinguishing effects arising from $\delta_{CP}$ and matter. In this paper we show how this comprehensive physics case can be further enhanced and complemented if a neutrino beam produced at the Protvino IHEP accelerator complex, at a distance of 1160 km, and with modest power of 450 kW is aimed towards the same far detectors. We show that the coupling of two independent sub-MW conventional neutrino and antineutrino beams at different baselines from CERN and Protvino will allow to measure CP violation in the leptonic sector at a confidence level of at least $3\sigma$ for 50\% of the true values of $\delta_{CP}$ with a 20 kton detector. With a far detector of 70 kton, the combination allows a $3\sigma$ sensitivity for 75\% of the true values of $\delta_{CP}$ after 10 years of running. Running two independent neutrino beams, each at a power below 1 MW, is more within today's state of the art than the long-term operation of a new single high-energy multi-MW facility, which has several technical challenges and will likely require a learning curve.Comment: 21 pages, 12 figure

Muscle Fiber Viability, a Novel Method for the Fast Detection of Ischemic Muscle Injury in Rats

Acute lower extremity ischemia is a limb- and life-threatening clinical problem. Rapid detection of the degree of injury is crucial, however at present there are no exact diagnostic tests available to achieve this purpose. Our goal was to examine a novel technique - which has the potential to accurately assess the degree of ischemic muscle injury within a short period of time - in a clinically relevant rodent model. Male Wistar rats were exposed to 4, 6, 8 and 9 hours of bilateral lower limb ischemia induced by the occlusion of the infrarenal aorta. Additional animals underwent 8 and 9 hours of ischemia followed by 2 hours of reperfusion to examine the effects of revascularization. Muscle samples were collected from the left anterior tibial muscle for viability assessment. The degree of muscle damage (muscle fiber viability) was assessed by morphometric evaluation of NADH-tetrazolium reductase reaction on frozen sections. Right hind limbs were perfusion-fixed with paraformaldehyde and glutaraldehyde for light and electron microscopic examinations. Muscle fiber viability decreased progressively over the time of ischemia, with significant differences found between the consecutive times. High correlation was detected between the length of ischemia and the values of muscle fiber viability. After reperfusion, viability showed significant reduction in the 8-hour-ischemia and 2-hour-reperfusion group compared to the 8-hour-ischemia-only group, and decreased further after 9 hours of ischemia and 2 hours of reperfusion. Light- and electron microscopic findings correlated strongly with the values of muscle fiber viability: lesser viability values represented higher degree of ultrastructural injury while similar viability results corresponded to similar morphological injury. Muscle fiber viability was capable of accurately determining the degree of muscle injury in our rat model. Our method might therefore be useful in clinical settings in the diagnostics of acute ischemic muscle injury

Radionuclide imaging of bone marrow disorders

Noninvasive imaging techniques have been used in the past for visualization the functional activity of the bone marrow compartment. Imaging with radiolabelled compounds may allow different bone marrow disorders to be distinguished. These imaging techniques, almost all of which use radionuclide-labelled tracers, such as 99mTc-nanocolloid, 99mTc-sulphur colloid, 111In-chloride, and radiolabelled white blood cells, have been used in nuclear medicine for several decades. With these techniques three separate compartments can be recognized including the reticuloendothelial system, the erythroid compartment and the myeloid compartment. Recent developments in research and the clinical use of PET tracers have made possible the analysis of additional properties such as cellular metabolism and proliferative activity, using 18F-FDG and 18F-FLT. These tracers may lead to better quantification and targeting of different cell systems in the bone marrow. In this review the imaging of different bone marrow targets with radionuclides including PET tracers in various bone marrow diseases are discussed

Performance study of a 3 x 1 x 1 m(3) dual phase liquid Argon Time Projection Chamber exposed to cosmic rays

This work would not have been possible without the support of the Swiss National Science Foundation, Switzerland; CEA and CNRS/IN2P3, France; KEK and the JSPS program, Japan; Ministerio de Ciencia e Innovacion in Spain under grants FPA2016-77347-C2, SEV-2016-0588 and MdM-2015-0509, Comunidad de Madrid, the CERCA program of the Generalitat de Catalunya and the fellowship (LCF/BQ/DI18/11660043) from "La Caixa" Foundation (ID 100010434); the Programme PNCDI III, CERN-RO, under Contract 2/2020, Romania; the U.S. Department of Energy under Grant No. DE-SC0011686. This project has received funding from the European Union's Horizon 2020 Research and Innovation program under Grant Agreement no. 654168. The authors are also grateful to the French government operated by the National Research Agency (ANR) for the LABEX Enigmass, LABEX Lyon Institute of Origins (ANR-10-LABX-0066) of the Universite de Lyon for its financial support within the program "Investissements d'Avenir" (ANR-11-IDEX-0007).We report the results of the analyses of the cosmic ray data collected with a 4 tonne (3x1x1 m(3)) active mass (volume) Liquid Argon Time-Projection Chamber (TPC) operated in a dual-phase mode. We present a detailed study of the TPC's response, its main detector parameters and performance. The results are important for the understanding and further developments of the dual-phase technology, thanks to the verification of key aspects, such as the extraction of electrons from liquid to gas and their amplification through the entire one square metre readout plain, gain stability, purity and charge sharing between readout views.Swiss National Science Foundation (SNSF)French Atomic Energy CommissionCentre National de la Recherche Scientifique (CNRS)High Energy Accelerator Research Organization (KEK)Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceSpanish Government FPA2016-77347-C2 SEV-2016-0588MdM-2015-0509Comunidad de MadridCERCA program of the Generalitat de CatalunyaLa Caixa Foundation LCF/BQ/DI18/11660043 100010434Programme PNCDI III, RomaniaCERN-RO, Romania 2/2020United States Department of Energy (DOE) SC0011686European Commission 654168Universite de Lyon ANR-10-LABX-0066 ANR-11-IDEX-000

Comparação termohigrométrica de sub-altitude em área urbana e rural em São Carlos, Brasil, por meio de VANT/DRONE.

A Radiossondagem de sub-altitude tem como objetivo mensurar os dados climatológicos em vários níveis verticais da atmosfera por meio de um equipamento denominado radiossonda. Além do mais, é conhecido que os diferentes tipos de uso e ocupação do solo (urbano, industrial, rural, florestal) alteram o balanço de energia entre a superfície e a atmosfera. Dessa forma, o estudo proposto tem como objetivo analisar e comparar os valores de temperatura e umidade relativa do ar próximo a superfície (1,5m de altura) e em diferentes alturas (50m e 190m da superfície) em área urbana e rural no município de São Carlos, Brasil, no período noturno em episódios de inverno, por meio de termohigrômetros acoplados em um Veículo Aéreo Não-Tripulado (Vant/Drone) do tipo quadricóptero (quatro hélices). O voo na área urbana foi realizado no dia 13/07/2018 e na área rural no dia 26/07/2018 entre 19:30 e 20:30. Os resultados demonstraram que na área urbana em períodos noturnos a temperatura e umidade relativa do ar são maiores próxima a superfície em relação aos dados de sub-altitude. Já na área rural em períodos noturnos a temperatura do ar é menor e a umidade relativa do ar é maior próximo a superfície em comparação aos dados de sub-altitude

Tromboelastografía

15 páginasMaintaining blood in a liquid state is critical for homeostasis. It allows blood to supply adequate oxygen and nutrients to tissues while also eliminating carbon dioxide and other waste products. On the other hand, the ability of blood to convert from a liquid to a solid state, in other words, to coagulate, underlies the mechanism that protects the body from life-threatening exsanguination. This process of thrombosis is normally a localized event at the site of vascular injury while the rest of the circulating blood remains in a liquid state. Thrombosis is a dynamic process that includes associated thrombolysis to maintain or restore blood flow through vessels once an injury has been sealed. These unique properties of blood are largely determined by a complex and active balance between pro-coagulation factors, anticoagulants, and fibrinolysis. Two major pathologic conditions are commonly associated with disequilibrium of this intricate system: bleeding and vessel thrombosis. Major bleeding is a serious medical complication that may be caused by external trauma, surgery, invasive procedures, or an underlying medical condition such as aneurysm rupture or peptic ulcer disease. According to the World Health Organization (WHO), injuries are responsible for 5.8 million deaths per year worldwide, with the associated bleeding responsible for about 30% to 40% of these deaths. Several congenital disorders associated with a coagulation factor deficiency, such as Von Willebrand disease, hemophilia A or B, may cause significant bleeding even with minor injuries. Also, prescribed anticoagulants and antiplatelet agents may create a coagulopathic state that may lead to excessive bleeding either associated with trauma or medical procedures. Finally, major acute blood loss can lead to coagulopathy due to a loss of coagulation factors. Predictably, trauma-related coagulopathy has been associated with significantly higher mortality. Patients with ongoing or expected major bleeding would benefit from an accurate assessment of the functional state of the hemostatic system to provide optimal care, providing cost-effective replacement of only the needed blood components. Venous thromboembolism (VTE) is another common and serious condition that is associated with abnormal blood coagulation. In these cases, systemic hypercoagulability shifts the body’s homeostatic mechanisms toward a pro-thrombotic state. In particular patients, however, a definitive cause for the VTE may be unclear. Routine coagulation testing has not been shown to predict such events, and in many cases, even a detailed hypercoagulability investigation fails to identify an underlying disorder. Many people take anticoagulants and antiplatelet agents regularly, which impacts the accuracy of the results of many laboratory coagulation studies. An accurate and cost-efficient method of monitoring antithrombotic activity would be helpful to maintain an acceptable risk/benefit ratio in such patients. Inadequate anticoagulation or antiplatelet therapy can lead to devastating thromboembolic conditions. Several commonly used blood tests assess blood coagulation. These tests include prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), platelet count, fibrinogen concentration, D-dimer level, activated clotting time, and whole blood bleeding time (BT). These tests are usually used for the clinical diagnosis of coagulopathy and a possible prothrombotic state, to monitor anticoagulation therapy, and to assist in treating bleeding episodes. More specific factor analyses, such as Factor V, proteins C and S, anti-thrombin III, anticardiolipin antibodies, and prothrombin gene mutation, are useful but not as readily available in emergency clinical situations. Despite being very effective for specific clinical needs, such as anticoagulation monitoring, the first group of usual diagnostic tests has limitations. Their main disadvantage in circumstances of acute major bleeding is the long turnaround time. Furthermore, they do not provide a complete picture of hemostasis due to their inability to assess some coagulation factors (such as Factor XIII), platelet function, and the activity of the fibrinolytic system. Platelet concentration, easily measured as part of a complete blood count, does not necessarily reflect their function, especially in the presence of elements known to affect platelet reactivity, such as non-steroidal anti-inflammatory drugs, antiplatelet agents, uremia, malignancy, or alcohol intake. Bleeding time has a low sensitivity and high inconsistency in detecting platelet disorders. Delayed or inadequate diagnosis of coagulopathy in a bleeding patient may lead to an excessive and improperly balanced transfusion of scarce blood components with increased morbidity, treatment costs, and mortality. Thromboelastography (TEG) is a promising diagnostic modality that offers several advantages compared to the other tests that have been mentioned above. TEG was developed and first described by Dr. Hellmut Hartert at the University of Heidelberg (Germany) in 1948. The first reported clinical application of the test occurred during the Vietnam War in an attempt to guide transfusions of blood components in injured soldiers. In the 1980s, TEG was found to be beneficial in liver transplant patients, and in the 1990s, it was demonstrated to be useful in cardiac surgery. Since then, TEG has evolved into a more commonly used test as more evidence for its clinical efficacy has been attained. A brief search in PubMed using keywords “thromboelastography” and “thromboelastometry” results in about 6000 publications. This article will describe the general principles of TEG, methodology, normal values, along with the current evidence and clinical applications, as well as limitations and future research directions.Mantener la sangre en estado líquido es fundamental para la homeostasis. Permite que la sangre suministre el oxígeno y los nutrientes adecuados a los tejidos, al tiempo que elimina el dióxido de carbono y otros productos de desecho. Por otra parte, la capacidad de la sangre de pasar de estado líquido a sólido, es decir, de coagularse, es la base del mecanismo que protege al organismo de un desangramiento potencialmente mortal. Este proceso de trombosis es normalmente un acontecimiento localizado en el lugar de la lesión vascular, mientras que el resto de la sangre circulante permanece en estado líquido. La trombosis es un proceso dinámico que incluye la trombólisis asociada para mantener o restablecer el flujo sanguíneo a través de los vasos una vez sellada la lesión. Estas propiedades únicas de la sangre vienen determinadas en gran medida por un equilibrio complejo y activo entre los factores procoagulantes, los anticoagulantes y la fibrinólisis. El desequilibrio de este intrincado sistema suele estar asociado a dos patologías principales: la hemorragia y la trombosis vascular