A fluorescent probe assay (Heparin Red) for direct detection of heparins in human plasma.

Heparins are widely used anticoagulant drugs. The current monitoring practice for heparin in plasma, such as the chromogenic anti-factor Xa assay, relies on heparin-triggered activation of antithrombin, an inhibitor of coagulation proteases. Such assays are not applicable to the detection of non-anticoagulant heparins, an emerging class of drug candidates for therapeutic applications unrelated to anticlotting activity. This study describes the application of a commercially available fluorescent probe assay (Heparin Red) for the direct and sensitive detection of the "chemical" heparin in plasma, independent of any anticoagulant activity. The quantification range is about 0-5 µg/mL for both unfractionated heparin (corresponding to 0-1 IU/mL) and the low molecular weight heparin enoxaparin. The Heparin Red assay is of particular value for the quantification of non-anticoagulant heparins, as exemplified by the low molecular weight heparin derivative tafoxiparin and a N-desulfated-N-reacetylated heparin. Heparin octa- and decasaccharides are also detected. Graphical abstract Heparin quantification in plasma by mixing the sample with the Heparin Red reagent and fluorescence readout.

[Stress parameters and behaviour of horses in walkers with and without the use of electricity]. / Stressbelastung und Verhalten von Pferden in stromführenden gegenüber nicht stromführenden Führanlagen.

In order to investigate stress responses of horses in walkers with and without electricity, 12 horses were trained during 3 weeks in a horse walker with and without the use of electricity (3.7 kV). To evaluate the stress response, cortisol levels in the blood were measured, the heart rate was monitored using the Polar® system and the behaviour was evaluated. Neither the cortisol levels nor the heart rates showed any relevant statistically significant difference between horses moved in the horse walker with or without the use of electricity. The highest cortisol levels and heart rates were recorded during the first week (habituation period). A significant difference could be observed regarding spontaneous compartment changes: while this happened mainly during the first week and before the first use of electricity, no horses changed compartments in the periods when electricity was used and thereafter. The results of this study indicate that the use of electricity in the horse walker does not seem to cause significant detectable stress in the horses.

Pour comparer le stress ressenti par les chevaux dans les marcheurs, on a placé 12 chevaux durant 3 semaines dans un marcheur avec ou sans courant électrique (3.7 kV) dans les séparations. On a mesuré le taux de cortisol sanguin et la fréquence cardiaque au moyen d'un appareil Polar® et noté le comportement des chevaux. Ni les taux de cortisol ni les fréquences cardiaques ne présentaient de différences significatives entre les chevaux placés dans un marcheur avec ou sans courant électrique dans les séparations. Les taux de cortisol et les fréquences cardiaques les plus élevés ont été observés dans la première semaine (phase d'accoutumance). Des différences significatives de comportement ont par contre été constatées quant aux paramètres «changement spontané de compartiment¼ et «contact avec la séparation¼: alors que ces faits se produisaient particulièrement durant la première semaine et avant le premier usage du courant électrique, les chevaux ne changeaient plus de compartiment pendant et après l'emploi de l'électricité. Les résultats de cette étude indiquent que l'emploi de l'électricité dans les séparations des marcheurs ne cause pas de stress mesurable significatif pour les chevaux.

Formation and relaxation of RbHe exciplexes on He nanodroplets studied by femtosecond pump and picosecond probe spectroscopy.

Vibrationally resolved photoionization spectra of RbHe exciplexes forming on He nanodroplets are recorded using femtosecond pump-probe spectroscopy with amplitude-shaped probe pulses. The time-evolution of the spectra reveals an exciplex formation time ~10 ps followed by vibrational relaxation extending up to ≳ 1 ns. This points to an indirect, time-delayed desorption process of RbHe off the He surface.

Coherent population trapping with controlled interparticle interactions.

We investigate coherent population trapping in a strongly interacting ultracold Rydberg gas. Despite the strong van der Waals interactions and interparticle correlations, we observe the persistence of a resonance with subnatural linewidth at the single-particle resonance frequency as we tune the interaction strength. This narrow resonance cannot be understood within a mean-field description of the strong Rydberg-Rydberg interactions. Instead, a many-body density matrix approach, accounting for the dynamics of interparticle correlations, is shown to reproduce the observed spectral features.

Network visualization for outbreak response: Mapping the Ebola Virus Disease (EVD) chains of transmission in N'Zérékoré, Guinea.

BACKGROUND: During the 2014-2015 Ebola Virus Disease (EVD) outbreak in N'Zérékoré, Forested Guinea, modes of transmission remained unexamined for a number of new cases. We used network visualization to investigate EVD transmission chains (TC) in seven sub-prefectures of N'Zérékoré in order to adapt outbreak response. METHODS: Between August 2014 and February 2015, the EVD outbreak response team including the World Health Organization (WHO) and local health authorities routinely collected information among new cases regarding hospital visits, cases within a household, participation in burials, as well as dates of symptom onset, serial intervals (SI) and exposure to EVD. SI's were defined as the interval between symptom onset in an index case and symptom onset in a secondary case infected by that index case. Cases who reported hospital visits, contact with a case in the household or participating in burials were attributed to these exposures. RESULTS: We identified seven TC (two urban and five rural) gathering characteristics of 109 probable/confirmed cases. Overall, 61% (66 cases, SI range: 7-20 days) were household related, 32% (35 cases, SI range 8-30 days) were household or burial related and 7% (8 cases, SI range: 4-20 days) were hospital-related. In the urban chains (18 cases, SI range: 7-20 days), 12 cases were household related and 6 cases were hospital related, none where household or burial related. In the rural chains (84 cases, SI range: 7-30 days), 60% (50 cases) were household related, 1% (1 case) was hospital related and 39% (34 cases) were household or burial related. No cases reported multiple exposures. CONCLUSIONS: Network visualization during field response is crucial in enhancing local control strategies, refining outbreak response and aiding rapid response teams in insuring psychosocial and socio-economic recovery. Urban settings need to focus on reducing hospital EVD transmission whereas rural settings should focus on raising awareness of transmission within a household and safeguarding EVD burials.

Effect of dried garlic on blood coagulation, fibrinolysis, platelet aggregation and serum cholesterol levels in patients with hyperlipoproteinemia.

The effects of intake of dried garlic on blood coagulation, fibrinolysis, platelet aggregation, serum cholesterol levels, and blood pressure were studied in 20 patients with hyperlipoproteinemia over a period of four weeks. Fibrinogen and fibrinopeptide A significantly decreased by 10%. Streptokinase activated plasminogen and fibrinopeptide B beta 15-42 significantly increased by about 10%. Serum cholesterol levels significantly decreased by 10%. Systolic and diastolic blood pressure decreased. ADP and collagen induced platelet aggregation were not influenced.

Biological activity and safety of the subcutaneous administration of high doses of low molecular weight heparin for 8 days in human volunteers.

This study reports on the biological activity and safety of high dose low molecular weight (LMW) heparin therapy administered by two subcutaneous (s.c.) injections daily for 8 days in healthy human volunteers. Group 1 received 2 x 30 aPTT units LMW heparin/kg bodyweight, and group 2 received 2 x 50 aPTT units/kg per day. In group 1, activated partial thromboplastin time (aPTT) and thrombin clotting time (TCT) were uniformly prolonged by 3-5 sec 4 hrs after s.c. administration of heparin. Heptest coagulation time values were prolonged consistently as well by 57 sec on day 1 to 68 sec on day 8. Factor Xa inhibition measured by the S 2222 chromogenic substrate method continuously increased from 0.16 units/ml on day 1 to 0.28 units/ml on day 8. In group 2 prolongation of a aPTT and TCT values increased from 6 sec on day 1 to 15 sec on day 8 and of Heptest time from 70 sec on day 1 to 110 sec on day 8. S 2222 method showed factor Xa inhibitory activity which increased from 0.5 units/ml on day 1 to 0.75 units/ml on day 8. The clinical tolerance of the treatment was good. No changes in clinical chemistry parameters were detected, except for a reversible increase of serum transaminases. The coagulation studies demonstrate accumulation of LMW heparin when high doses are given twice daily. The half life of LMW heparin of factor Xa inhibition increases with increasing doses. Heptest coagulation values were prolonged to 4-6 times the normal values during administration of heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

Monitoring of heparin and low molecular weight heparin with capillary and venous whole blood.

A method for determination of antifactor Xa-like activity in capillary whole blood obtained from the fingertip is described, which employs the Heptest coagulation assay. Values obtained with capillary whole blood are compared to values of corresponding plasma and venous whole blood samples. Normal values in plasma, venous whole blood, and capillary blood from the fingertip were 17.1 +/- 2.1, 10.0 +/- 1.3 and 10.4 +/- 1.3 sec, respectively. The intraindividual coefficients of variations range from 0.4 to 1.8% in all assays. The day to day coefficient of variation of normal values ranged between 0.8 and 2.0% for all assays. The within assay coefficients of variation ranged from 3.0 to 7.7% for whole blood samples and from 1.5 to 2.2% for plasma samples after addition of no, 0.2 or 1.0 units of normal or LMW heparin to the samples. After administration of heparin or LMW heparin in healthy persons the coagulation values of the different coagulation assay systems displayed coefficients of correlation between r = 0.87 and r = 0.95. Correlation coefficients between the coagulation tests and the S 2222 chromogenic substrate method ranged from r = 0.77 to r = 0.92. In patients, who received LMW heparin for prophylaxis of thromboembolism the coagulation assay correlated between r = 0.78 and 0.92. The coagulation assays and the S 2222 method displayed coefficients of correlation between r = 0.74 and r = 0.83. The data indicate that Heptest sensitively measures antifactor Xa-like activity in capillary whole blood as well as venous whole blood samples containing low quantities of heparin or LMW heparin.

Sub-miniature ExB sector-field mass spectrometer.

A novel sub-miniature double-focusing sector-field mass spectrometer has been fabricated at the University of Minnesota using a combination of conventional machining methods and thin film patterning techniques typically used in the sensor technology industry. Its design is based on the mass separation capabilities of a 90 degrees cylindrical crossed electric and magnetic sector-field analyzer with a 2-cm radius, which under proper conditions is able to effectively cancel the angular and chromatic dispersion of the ion beam, thus improving the resolving power of the instrument. Simulations using finite element analysis and computer modeling were employed to verify and optimize the performance of the proposed instrument before and during its fabrication. The prototype was able to attain a resolving power of 106 full-width at half-maximum (FWHM), a detection limit close to 10 parts per million, a dynamic range of 5 orders of magnitude and a mass range up to 103 Da. Its overall size, including the magnet assembly, is 3.5 cm wide, 6 cm long and 7.5 cm tall, it weighs 0.8 kg, and its power consumption was measured to be 2.5 W. The performance of the instrument was found to be comparable to that of commercial residual gas analyzers, at a fraction of the cost. All these characteristics make this miniature mass spectrometer suitable for portable and low-cost analytical instrumentation.

Studies on the immunomodulatory effects of anthracycline antibiotics in mice: effects on immune responses and graft immunogenicity.

The immunomodulatory effects of adriamycin, a clinically used tumor antibiotic, were studied. A 5-day course of adriamycin therapy in mice led to a suppression of the primary but not of the secondary humoral response to sheep erythrocytes without significant alterations in peripheral blood leukocyte subsets or lymphocyte subpopulations in the spleen. The delayed type hypersensitivity (DTH) response to ovalbumin or alloantigens was not inhibited. Adriamycin-treated spleen cells were unable to stimulate an allogeneic mixed leukocyte reaction, which shows that antigen presentation is inhibited by this drug. Adriamycin-treated murine skin grafts show a prolonged survival after allotransplantation despite their unimpaired ability to induce DTH. The possible cellular mechanisms of these effects and clinical relevance of adriamycin are discussed.

Resistance and vulnerability of crustaceans to cytolytic sea anemone toxins.

Crustaceans (Mithraculus, Neopetrolisthes, Periclimenes, Stenorhynchus sp.) living in association with sea anemones, shore crabs (Metopograpsus oceanicus) and brine shrimps (Artemia salina) were found to be resistent to the exposure of cytolytic sea anemone toxins (up to 100 micrograms/ml) and to other membrane-active compounds such as gramicidin A and saponin. The gill filaments of the crustaceans were not affected, indicating that the chitin layer protects the epithelium from the action of the cytolytic toxins. However, crustaceans are highly susceptible to sea anemone toxins when injected parenterally.

Dynamics of low-energy helium vapor pulses.

We report results of experiments in which pulses of helium vapor are produced by a current pulse in a chromium film covered with superfluid helium at around 0.3 K. The pulses were detected by a titanium bolometer operating at 0.47 K. The shape of the detected signal is a strong function of the power of the initiating current pulse. For low powers the signal from a single current pulse also contains a single peak, but for higher powers, a single current pulse produces two and then at the highest powers, three peak signals. To analyze the origin of these phenomena we report results of hybrid gas-dynamics and hydrodynamics simulations, which demonstrate that the signals arise from shock waves formed in the vapor. The shock waves form due to the presence of a gradient in the small ambient background of helium vapor in the chamber and are extremely sensitive to the pulse power.

Ten-microsecond pulsed molecular beam source and a fast ionization detector.

We describe a pulsed gas valve which we have developed for use as a molecular beam source. In order to observe the performance of the pulsed beam source, we also have developed an ionization detector with a rise time of about 1 micros. The pulsed valve produces very intense supersonic molecular beam pulses of about 10 micros duration for light gases such as H2 and He, and of somewhat longer duration for heavier gases. As a new tool for the study of molecular collisions, the pulsed beam technique offers substantial advantages over the conventional continuous-beam method for experiments which are limited by the signal-to background ratio for scattered products.

[History of veterinary medicine as a branch of learning--lessons and possibilities]. / Geschichte der Veterinärmedizin als Lehrfach--Aufgaben und Möglichkeiten.

History of veterinary medicine--which has always been under-rated in the curricula--is the only discipline within the professional training of a veterinary surgeon which encompasses all subjects. It therefore has a uniting, virtually encyclopaedic, mediating function. The intention of a lecture must be to impart a historic view, to inspire the students to consider the responsibility which man has for animals, and to make them sensitive in their professional life for a critical reflection of the basic intellectual concepts of our time and our society beyond the limits of their knowledge of veterinary medicine. It is the veterinary surgeon's "professional culture"--and an essential part of it is the history of veterinary medicine and domestic animals--which demands that this permanent reflection be the basis for the meaningful work of a veterinary surgeon.

["With effort and much pain and an unspeakable, truly stupid patience." Theodor Ludwig Wilhelm von Bischoff (1807-1882) as an embryologist]. / "Mit Aufwand und vieler Mühe und einer unsäglichen, wahrhaft stupiden Geduld" Theodor Ludwig Wilhelm von Bischoff (1807-1882) als Embryologe.

Theodor L. W. von Bischoff (1807-1882), who worked as an anatomist and physiologist in Heidelberg, Giessen and Munich, is among the most excellent embryologists of the 19th century. His work on the history of development of mammals and of man (1842), his finding proof of spontaneous periodic ovulation in mammals (1844), but above all his directive monographies on rabbits, dogs, guinea pigs and deer (1842-1854) provided the most comprehensive research into the history of the development of mammals which had been done so far. He was less successful, however, with his physiological research including a project on urea as a measure for metabolic activity (1853) which had been initiated by Justus Liebig. The same is true for his studies of the weight of the human brain and his comparative anatomical research into the anatomy of the skull and brain of primates, which had been his main interest since 1860. Bischoff, who had been raised to nobility for his merits, did not confine his activities to science, but engaged in questions of medical education and in the politics of his profession as a member of influential committees, fiercely opposing the admission of women to medical studies (1872).