Evaluation of ^(99m)Tc Labeled Diadenosine Tetraphosphate as an Atherosclerotic Plaque Imaging Agent in Experimental Models

The potential of ^99mTc labeled P^1, P^4-di （adenosine-5 ＇ ）-tetraphosphate （Ap4A） for imaging experimental atherosclerotic plaques was evaluated in New Zealand white （NZW） rabbits. To label the ^99mTc to Ap4A, stannous tartrate solution was used. ^99mTc-Ap4A was purified on a Sephadex G-25 column. The radiochemistry purities of ^99mTc-Ap4A were 85% to 91%. Biodistribution study revealed ^99mTc-Ap4A cleared from blood rapidly. Thirty min after ^99mTc-Ap4A administrated on NZW atherosclerotic rabbits, lesion to blood （target/blood, T/B） ratio was 3. 17 ±1.27, and lesions to normal （target/non-target, T/NT） ratio was 5.23 ±1.87. Shadows of atherosclerotic plaques were clearly visible on radioautographic film. Aortas with atherosclerotic plaques also could be seen on ex vivo gamma camera images. Atherosclerotic abdominal aortas were clearly visible on in vivo images 15 min to 3 h after ^99mTc-Ap4A administration. ^99mTc-labeled Ap4A can be used for rapid noninvasive detection of experimental atherosclerotic plaque.

Pyronaridine combined with diminazene aceturate inhibits Babesia in vitro and in vivo

Objective:To evaluate the combination therapy of pyronaridine tetraphosphate and diminazene aceturate against Babesia in vitro and in vivo.Methods:Bioinformatic analysis was performed using atom pair fingerprints.An in vitro combination test was performed against Babesia bovis and Theileria equi.Moreover,the in vivo chemotherapeutic efficacy of pyronaridine tetraphosphate in combination with diminazene aceturate was investigated against the growth of Babesia microti in mice using a fluorescence inhibitory assay.Results:Pyronaridine tetraphosphate and diminazene aceturate exhibited nearly similar molecular weights.The in vitro combination of pyronaridine tetraphosphate and diminazene aceturate was synergistic on Babesia bovis and additive on Theileria equi.In addition,5 mg/kg pyronaridine tetraphosphate combined with 10 mg/kg diminazene aceturate inhibited Babesia microti growth significantly compared with those observed after treatment with 25 mg/kg diminazene aceturate alone from day 6 post treatment to day 12 post treatment.The combination therapy also normalized the hematological parameters of infected mice.Conclusions:An oral dose of pyronaridine tetraphosphate combined with a subcutaneous dose of diminazene aceturate inhibits Babesia in vitro and in mice,suggesting it might be a new paradigm for the treatment of babesiosis.

Synthesis of nucleoside tetraphosphates and dinucleoside pentaphosphates from nucleoside phosphoropiperidates via the activation of P(V)-N bond

A novel and efficient method for the preparation of nucleoside 5＇-tetraphosphates has been developed by coupling nucleoside 5＇-phosphoropiperidates with triphosphate reagent in the presence of 4, 5-dicyanoimidazole （DCI） activator. Further coupling of the nucleoside 5＇-tetraphosphates with nucleoside 5＇-phosphoropiperidates via the P（V）-N activation strategy provided a reliable synthetic method for both symmetrical and asymmetrical dinucleoside pentaphosphates.

Magnetic and XPS studies of lithium lanthanide tetraphosphates LiLnP_4O_(12)(Ln=Nd,Gd,Er)

Magnetic susceptibilities of flux-grown single crystals of LitnP4012 （Ln=Nd, Gd, Er） were measured in the temperature range of 2-300 K. The compounds were paramagnetic, and obeyed the Curie-Weiss law in the entire temperature interval, without magnetic phase transitions, and with effective magnetic moments close to those of the corresponding free Ln3＋ ions. X-ray photoelec- tron spectroscopy was applied to determine the positions of core-level electrons relative to the Fermi level： Li is; Ln 4f, 5p, 5s, 4d, 3d; P 2s, 2p; O 1s, 2s. The binding energies in these compounds were found slightly shifted compared to the respective values of the same elements.

Mathematical model for the ubiquitin activating enzyme E1

The ubiquitin-activating enzyme E1 (EC 6.3.2.19) represents the first step in the degradation of proteins by the ubiquitin proteasome pathway. E1 transfers ubiquitin from the ubiquitinated E1 to the ubiquitin carrier proteins (E2), ubiquitin-protein ligases (E3) and proteins. This process is rather complex, and known from the work of Haas, Ciechanover, Hershko, Rose and others. The occurrence of 19 hypothetical intermediate enzyme forms (EFs) and 22 different reactions were considered in the presence of ubiquitin (Ub), ATP, adenosine 5’-tetraphosphate (p4A), pyrophosphate (P2), and tripolyphosphate (P3) as substrates, and iodoacetamide (IAA) and dithioth- reitol (DTT) as inhibitors. Inspired by the work of Cha (Cha (1968) J. Biol. Chem., 243, 820-825) we have treated these reactions in two complementary ways: in rapid equilibrium and in steady state. The kinetics of both types of reactions were simulated and solved with a system of ordinary differential equations using the Mathematica Program. The ubiquitination of E1 has been also theoretically coupled to the ubiquitination of E2, E3 and proteins. This makes the model useful to predict the theoretical influence of inhibitors (or of changes in some parameters of the reaction) on the ubiquitination of proteins. The Program responds to changes in the concentration of ATP or ubiquitin and has predictive properties as shown by the influence of AMP on the synthesis of p4A, calculated theoretically and confirmed experimentally.