Long Acting, Reversible Veterinary Sedative and Analgesic and Method of Use

A veterinary composition comprising a guanidine derivative, e.g., guanabenz or guanabenz acetate is provided which produces a rapid acting and long lasting sedative and analgesic effect in a subject animal that is selectively reversible. The use of guanabenz in the horse provides for a safe, effective, long lasting and rapidly reversible sedative and analgesic which can be used on the standing animal. Methods of use of the compositions of the invention are also provided

Homodyne detection for laser-interferometric gravitational wave detectors

Gravitational waves are ripples of space-time predicted by Einstein\u27s theory of General Relativity. The Laser Interferometer Gravitational-wave Observatory (LIGO), part of a global network of gravitational wave detectors, seeks to detect these waves and study their sources. The LIGO detectors were upgraded in 2008 with the dual goals of increasing the sensitivity (and likelihood of detection) and proving techniques for Advanced LIGO, a major upgrade currently underway. As part of this upgrade, the signal extraction technique was changed from a heterodyne scheme to a form of homodyne detection called DC readout. The DC readout system includes a new optical filter cavity, the output mode cleaner, which removes unwanted optical fields at the interferometer output port. This work describes the implementation and characterization of the new DC readout system and output mode cleaner, including the achieved sensitivity, noise couplings, and servo control systems

Size-Change Termination as a Contract

Termination is an important but undecidable program property, which has led to a large body of work on static methods for conservatively predicting or enforcing termination. One such method is the size-change termination approach of Lee, Jones, and Ben-Amram, which operates in two phases: (1) abstract programs into "size-change graphs," and (2) check these graphs for the size-change property: the existence of paths that lead to infinite decreasing sequences. We transpose these two phases with an operational semantics that accounts for the run-time enforcement of the size-change property, postponing (or entirely avoiding) program abstraction. This choice has two key consequences: (1) size-change termination can be checked at run-time and (2) termination can be rephrased as a safety property analyzed using existing methods for systematic abstraction. We formulate run-time size-change checks as contracts in the style of Findler and Felleisen. The result compliments existing contracts that enforce partial correctness specifications to obtain contracts for total correctness. Our approach combines the robustness of the size-change principle for termination with the precise information available at run-time. It has tunable overhead and can check for nontermination without the conservativeness necessary in static checking. To obtain a sound and computable termination analysis, we apply existing abstract interpretation techniques directly to the operational semantics, avoiding the need for custom abstractions for termination. The resulting analyzer is competitive with with existing, purpose-built analyzers

Pharmacokinetics and protein binding of morphine in horses

Morphine could be detected in horses dosed with 0.1 mg of drug/kg of body weight for up to 48 hours in blood and 144 hours in urine. This dose of morphine elicited no observ­able effects and is a suggested an­algesic dose. Computer analysis revealed that a 3-compartment open system was the best fitting model with a serum half life of 87.9 minutes and a urine half life of 101.1 minutes. Binding to equine serum proteins was linear over a drug con­centration range of 3.88 x 10-5M to 3.50 x 10-aM and averaged 31.6%. In RBC-partitioning experiments, 78.1 % of the drug was found in the plasma fraction. The data indicated that a horse should not be given morphine closer than 1 week before a race

Diclazuril Protects against Maternal Gastrointestinal Syndrome and Congenital Toxoplasmosis

BACKGROUND: Toxoplasmosis is a common cause of foodborne, gastrointestinal and congenital syndrome with particularly severe or unknown health consequences. There is no safe and effective preventive or therapeutic modality against congenital toxoplasmosis or to eliminate the persistent chronic infection. HYPOTHESIS: Diclazuril to be safe in pregnancy and effective against gastrointestinal toxoplasmosis. METHODS: CD1 programmed pregnant mice were divided into groups and administered a diet containing diclazuril, or sham control. Treatments were initiated on Day 5 of pregnancy and continued until Day 16 when dams were euthanatized. On Day 8 of pregnancy dams were infected intraperitoneally with escalating doses of tachyzoites (0, 100, 300, 600) from Type II strain. Dams were monitored daily for distress, pain, and abortion and samples collected at the end of the experiments. RESULTS: Infected dams developed moderate to severe Toxoplasma related complications in tachyzoites dose dependent manner. Animals became anemic and showed hydrothorax, and ascities. Diclazuril effectively protected dams from ascities and anemia (p \u3c 0.05). Infected dams showed splenomegaly, with massive infiltration of epithelioid cells compared with the protective effect of diclazuril in treated animals. Infected dams exhibited severe hepatitis (score 0 to 4 scale = 3.5 ± 0.01) with influx of inflammatory and plasma cells, dysplastic hepatocytes, multinucleated giant cell transformation and hepatic cells necrosis. Diclazuril treatment significantly protected dams from hepatitis, also in tachyzoites dose (100, 300, 600) dependent manner (respectively infected-treated versus infected controls, p \u3c 0.001, p \u3c 0.01 and p \u3c 0.05). Colonic tissues were significantly shortened in length, with infiltration of lymphocytes, and macrophages and microabscess formations in the cryptic structures, with significant improvement in diclazuril treated animals. Additionally, the number of fetuses, fetal length and fetal weight were preserved in diclazuril treated dams. CONCLUSIONS: This is the first report describing of diclazuril safety in pregnancy as well as efficacy against mild to moderate hepato-gastrointestinal syndrome in dams and fetal toxoplasmosis (Special issue, Treatment of Liver Diseases )

Formulations and Methods to Treat and Prevent Equine Protozoal Myeloencephalitis

The present invention provides formulations useful to treat EPM. It also provides methods to treat EPM in a horse in need of such treatment, comprising administering a pharmaceutically effective amount of a triazine-based anti-coccidial. Preferred are methods to treat EPM using clazuril, diclazuril, toltrazuril or letrazuril. The present invention also provides methods to prevent S. neurona infection in horses comprising administering a prophylactic amount of a triazine-based anticoccidial. Preferred is a method to prevent S. neurona infection by using clazuril, diclazuril, toltrazuril or letrazuril, alone or in combination with other known therapeutics

The pharmacologic effects of isoxsuprine

Isoxsuprine is a therapeutic medication used to treat navicular disease and other lower limb problems in horses and is one of the more frequently detected therapeutic agents in racing horses. In crossover studies, horses were administered intravenous and oral isoxsuprine to determine the character and duration of pharmacological effects. Following intravenous administration, isoxsuprine significantly increased heart rate, spontaneous activity, and sweat production. There was an apparent, although statistically insignificant, increase in cutaneous blood flow. Skin temperature decreased below control values, and there was a significant decrease in core temperature. Isoxsuprine also reduced smooth muscle tone. In contrast, after oral dosing, there was no statistical difference between control and isoxsuprine-treated horses for any of the measured variables. It was concluded that the measurable physiologic effects of intravenous isoxsuprine are short-lived, since none of the above responses was apparent four hours or more after intravenous administration