Pharmacokinetics of multiple doses of transdermal flunixin meglumine in adult Holstein dairy cows

A transdermal formulation of the nonsteroidal anti‐inflammatory drug, flunixin meglumine, has been approved in the United States and Canada for single‐dose administration. Transdermal flunixin meglumine was administered to 10 adult Holstein cows in their second or third lactation at the label dose of 3.33 mg/kg every 24 hr for three total treatments. Plasma flunixin concentrations were determined using high‐pressure liquid chromatography with mass spectroscopy (HPLC ‐MS ). Pharmacokinetic analysis was completed on each individual animal with noncompartmental methods using computer software. The time to maximum drug concentration (T max) was 2.81 hr, and the maximum drug concentration was 1.08 μg/ml. The mean terminal half‐life (T½) was determined to be 5.20 hr. Clearance per fraction absorbed (Cl/F) was calculated to be 0.294 L/hr kg^?1, and volume of distribution of fraction (V z/F ) absorbed was 2.20 L/kg. The mean accumulation factor was 1.10 after three doses. This indicates changes in dosing may not be required when giving multiple doses of flunixin transdermal. Further work is required to investigate the clinical efficacy of transdermal flunixin after multiple daily doses.     

Die Nachhaltigkeit von Düngungssystemen — Dargestellt am seehausener Düngungs‐Kombinationsversuch

Der 1967 in Seehausen auf sandigem Lehm angelegte Düngungs‐Kombinationsversuch dient der Analyse von Langzeitwirkungen gestaffelter Stallmist‐ und Mineral‐N‐Gaben (0,50,100,150 kg N ha^?1 a^?1) auf Pflanzen, Boden und Umwelt. Anhand von Meß‐, Bilanz‐ und Simulationswerten wird die Nachhaltigkeit dieser Düngungsvarianten bewertet.

Organisch‐mineralische Düngung führte zu Maximalerträgen von über 12t TM ha^?1 a^?1 und N‐Entzügen bis 200 kg ha^?1 a^?1. Der N‐Entzug der ungedüngten Variante betrug in den letzten Jahren noch etwa 75 kg ha^?1a^?1 gegenüber 100 kg ha^?1a^?1 zu Versuchsbeginn.

Die Entwicklung der Boden‐N_t‐Gehalte konnte mit e‐Funktionen beschrieben werden. Mineral‐N allein genügte nicht zum Erhalt der N_t‐Ausgangsvorräte, hierfür waren 55 bis 85 kg Stalldung‐N ha^?1 a^?1 notwendig. Die N_t‐ und C_t‐Gehalte korrelierten mit zahlreichen Bodenparametern. Hohe Humusgehalte forderten die biologische Aktivität.

Die N‐Verluste betrugen <10kg ha^?1 a^?1 (ungedüngt) bis 120 kg ha^?1a^?1 (höchstgedüngte Variante). Das N‐Verlustpotential lag bei Stallmistanwendung etwas niedriger als bei gleicher N‐Zufuhr in Mineralform. Je nach Stallmist‐Stufe waren 62 bis 104 kg Mineral‐N ha^?1 a^?1 erforderlich, um den Energieeinsatz je Produkteinheit zu minimieren.

Kombinierte Anwendung organischer und mineralischer Dünger (je 100 kg N ha^?1 a^?1) führte zu höchsten ökonomischen Leistungen, günstigen Bodeneigenschaften und tolerierbaren Umweltwirkungen. Zieht man alle verwendeten Nachhaltigkeitskriterien in Betracht, ist dieses Düngungssystem den anderen überlegen.     

Impact of an experimental PRRSV and Streptococcus suis coinfection on the pharmacokinetics of ceftiofur hydrochloride after intramuscular injection in pigs

This study determined the impact of porcine reproductive and respiratory syndrome virus (PRRSV) and Streptococcus suis coinfection on the pharmacokinetic (PK) profile of ceftiofur hydrochloride in pigs after intramuscular (i.m.) injection. Eighteen clinically normal crossbred gilts were assigned by weight into a challenge group (10 pigs) and control group (eight pigs). Pigs in both groups received a single i.m. injection of ceftiofur hydrochloride (Excenel RTU Sterile Suspension; Zoetis) at a 5 mg/kg BW dose. Serial blood samples were collected to characterize the plasma concentration curve. After a 10 days drug washout period, the challenge group was inoculated with 2 mL of PRRSV isolate VR‐2385 (10^5.75 50% tissue culture infective doses per mL) intranasally and 8 days later inoculated S. suis. When clinical disease was evident, the second PK assessment began in both challenge and control groups. Coinfected pigs demonstrated lower values of AUC and C_MAX, but higher values of Cl/F and Vz/F indicating drug kinetics were altered by infection. The data from this study have implications on ceftiofur treatment regimens in diseased pigs.     

Acanthocephalan infection and sparganosis in a green tree snake (Dendrelaphis punctulata)

Acanthocephalan and spargana parasites were identified within a body wall mass during exploratory surgery in a wild green tree snake. Acanthocephalan parasites have not previously been reported in this species. Surgical excision, the treatment of choice, could not be achieved because of the extensive infiltration of the coelomic cavity.     

Pharmacokinetics of firocoxib in preweaned calves after oral and intravenous administration

The objective of this study was to determine the pharmacokinetics of intravenous and oral firocoxib in 10 healthy preweaned calves. Firocoxib (0.5 mg/kg) was initially administered i.v. to calves, and following a 14‐day washout period, animals received firocoxib orally prior to cautery dehorning. Firocoxib concentrations were determined by liquid chromatography–tandem mass spectrometry. Changes in hematology and plasma chemistry were determined using automated methods. Computer software was used to estimate pharmacokinetic parameters best described with a two‐compartment model for i.v. administration and a one‐compartment model for p.o. administration. Following i.v. dosing, the geometric mean (range) T_1/2K10 and T_1/2β were 6.7 (4.6–9.7) and 37.2 (23.5–160.4) h, respectively, V_ss was 3.10 (2.10–7.22) L/kg, and CL was 121.7 (100.1–156.7) mL/h/kg. Following oral administration, geometric mean (range) C_max was 127.9 (102.5–151.3) ng/mL, T_max was 4.0 (2.6–5.6) h, and T_1/2K10 was 18.8 (14.2–25.5) h. Bioavailability of oral firocoxib was calculated using the AUC derived from both study populations to be 98.4% (83.1–117.6%). No adverse clinical effects were evident following firocoxib administration. Pharmacokinetic analysis of i.v. and p.o. firocoxib indicates high bioavailability and a prolonged terminal half‐life in preweaned calves.     

Probing the Local Effects of Magnetic Impurities on Superconductivity

The local effects of isolated magnetic adatoms on the electronic properties of the surface of a superconductor were studied with a low-temperature scanning tunneling microscope. Tunneling spectra obtained near magnetic adsorbates reveal the presence of excitations within the superconductor's energy gap that can be detected over a few atomic diameters around the impurity at the surface. These excitations are locally asymmetric with respect to tunneling of electrons and holes. A model calculation based on the Bogoliubov-de Gennes equations can be used to understand the details of the local tunneling spectra.     

Spontaneous formation of macroscopic chiral domains in a fluid smectic phase of achiral molecules

A smectic liquid-crystal phase made from achiral molecules with bent cores was found to have fluid layers that exhibit two spontaneous symmetry-breaking instabilities: polar molecular orientational ordering about the layer normal and molecular tilt. These instabilities combine to form a chiral layer structure with a handedness that depends on the sign of the tilt. The bulk states are either antiferroelectric-racemic, with the layer polar direction and handedness alternating in sign from layer to layer, or antiferroelectric-chiral, which is of uniform layer handedness. Both states exhibit an electric field-induced transition from antiferroelectric to ferroelectric.     

Organic Glasses: A New Class of Photorefractive Materials

The performance of amorphous organic photorefractive (PR) materials in applications such as optical data storage is generally limited by the concentration of active molecules (chromophores) that can be incorporated into the host without forming a crystalline material with poor optical quality. In polymeric PR systems described previously, performance has been limited by the necessity of devoting a large fraction of the material to inert polymer and plasticizing components in order to ensure compositional stability. A new class of organic PR materials composed of multifunctional glass-forming organic chromophores is described that have long-term stability and greatly improved PR properties.     

Coeval large-scale magmatism in the Kalahari and Laurentian cratons during Rodinia assembly

We show that intraplate magmatism occurred 1106 to 1112 million years ago over an area of two million square kilometers within the Kalahari craton of southern Africa, during the same magnetic polarity chron as voluminous magmatism within the cratonic core of North America. These contemporaneous magmatic events occurred while the Rodinia supercontinent was being assembled and are inferred to be parts of a single large igneous province emplaced across the two cratons. Widespread intraplate magmatism during Rodinia assembly shows that mantle upwellings required to generate such provinces may occur independently of the supercontinent cycle.     

Nanofabrication of Small Copper Clusters on Gold(111) Electrodes by a Scanning Tunneling Microscope

The use of scanning tunneling microscopy in an electrochemical environment as a tool for the nanoscale modification of gold electrodes was demonstrated. Small copper clusters, typically two to four atomic layers in height, were precisely positioned on a gold(111) electrode by a process in which copper was first deposited onto the tip of the scanning tunneling microscope, which then acted as a reservoir from which copper could be transferred to the surface during an appropriate approach of the tip to the surface. Tip approach and position were controlled externally by a microprocessor unit, allowing the fabrication of various patterns, cluster arrays, and "conducting wires" in a very flexible and convenient manner.