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Porphyrins are a unique class of biocompatible molecules with strong light absorption and rich coordination chemistry, leading to their use as chelating agents in applications such as biomedical imaging. In particular, clusters of chelators inside a nanoparticle core can be used as contrast agents for positron emission tomography. However, the mechanism of metal chelation by porphyrins encapsulated in the hydrophobic core of a nanoparticle, an essential step in radiolabeling, has not been addressed. Here, we present a study on the kinetics of copper chelation into hematoporphyrin derivative (HpD)-encapsulated nanoparticles. Nanoparticles of 100 nm, containing HpD and sterically stabilized by a poly(ethylene glycol) block copolymer, were prepared by the kinetically controlled, rapid precipitation process Flash NanoPrecipitation. When incubated with copper ions, these HpD nanoparticles exhibit novel chelation behavior. The experimental data on UV–vis absorption and reaction modeling of the two-step chelation reaction support the formation of an intermediate complex. The reaction rates of the initial binding and the final chelation step are kon= 0.231 h–1μM–1and kst= 1.095 h–1, respectively. The initial binding occurs within the first 20 min and converts to the firmly chelated, metalloporphyrin. Understanding the kinetics of the binding enables the next step in advancing this technology to medical diagnostics.

Nanoparticles (NP) are promising contrast agents for positron emission tomography (PET) radionuclide imaging that can increase signal intensity by localizing clusters of PET radionuclides together. However, methods to load NPs with PET radionuclides suffer from harsh loading conditions or poor loading efficacies or result in NP surface modifications that alter targeting in vivo. We present the formation of water-dispersible, polyethylene glycol coated NPs that encapsulate phthalocyanines into NP cores at greater than 50 wt % loading, using the self-assembly technique Flash NanoPrecipitation. Particles from 70 to 160 nm are produced. Phthalocyanine NPs rapidly and spontaneously chelate metals under mild conditions and can act as sinks for PET radionuclides such as 64-Cu to produce PET-active NPs. NPs chelate copper(II) with characteristic rates of 1845 M–1h–1at pH 6 and 37 °C, which produced >90% radionuclide chelation within 1 h. NP physical properties, such as core composition, core fluidity, and size, can be tuned to modulate chelation kinetics. These NPs retain 64Cu even in the presence of the strong chelator ethylene diamine tetraacetic acid. The development of these constructs for rapid and facile radionuclide labeling expands the applications of NP-based PET imaging.

Polymeric nanoparticles (NPs) have demonstrated their potential to induce antigen (Ag)-specific immunological tolerance in multiple immune models and are at various stages of commercial development. Association of Ag with NPs is typically achieved through surface coupling or encapsulation methods. However, these methods have limitations that include high polydispersity, uncontrollable Ag loading and release, and possible immunogenicity. Here, using antigenic peptides conjugated to poly(lactide-co-glycolide), we developed Ag-polymer conjugate NPs (acNPs) with modular loading of single or multiple Ags, negligible burst release, and minimally exposed surface Ag. Tolerogenic responses of acNPs were studied in vitro to decouple the role of NP size, concentration, and Ag loading on regulatory T cell (Treg) induction. CD4+CD25+Foxp3+Treg induction was dependent on NP size, but CD25 expression of CD4+T cells was not. NP concentration and Ag loading could be modulated to achieve maximal levels of Treg induction. In relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE), a murine model of multiple sclerosis, acNPs were effective in inhibiting disease induced by a single peptide or multiple peptides. The acNPs provide a simple, modular, and well-defined platform, and the NP physicochemical properties offer potential to design and answer complex mechanistic questions surrounding NP-induced tolerance.

It is well known that upper critical field, Hc2, in superlattices (SL) and layered superconductors (LS) is a nonlinear function of temperature,T, due to the so-called dimensional crossover. This nonlinearity manifests itself as well (via dependence of the vortex-lattice elastic moduli onHc2) at theH-Tphase diagram for vortex-lattice melting. We calculated the shape of a melting (irreversibility) line,Hm(T), in SL and LS taking into account thermal and quantum fluctuations as well as equation forHc2(T)in these systems in various regimes. In particular, the squareroot crossover ofHc2(T)results in a crossover from the power branchHm∝(Tc−T)a(a≤2) nearTcto the linear oneHm∝(T*−T) below someT*in agreement with the data on vortex melting in YBaCuO.

TO OUR knowledge there is no report in the English literature of attacks of apnea and cyanosis occurring with pyloric stenosis; consequently, we report the following case of this association in an infant. REPORT OF CASE A full term boy, weighing 7 pounds 8 ounces (3,402 Gm.), began to regurgitate and vomit shortly after birth. Mild regurgitation occurred after each feeding and vomiting about once in every 36 hours. There was sufficient absorption of nutriment, however, for maintenance. On the sixteenth day a period of sudden apnea accompanied with intense cyanosis occurred at the beginning of a feeding. Slapping the back with the infant in the inverted position restored the respiratory pattern. On the eighteenth day similar choking episodes accompanied with cyanosis occurred, with relief occurring again when the infant was turned upside down. On the twentieth day, while the infant was lying in his crib, about two hours after

Cefazolin, a new semisynthetic cephalosporin with a broad spectrum of antibiotic activity, was studied in a series of toxicologic experiments. It had a very low acute toxicity to mice and rats when administered both parenterally and orally. Cefazolin was not teratogenic for mice or rabbits and had no effect on the reproductive performance or on the offspring of rats treated prior to and during mating, gestation, and lactation. In experiments of subacute and chronic toxicity in rats and dogs, the major finding was damage to muscles following im injection. In studies of nephrotoxicity in rabbits, iv cefazolin, at doses of 300 mgtkg, produced degenerative changes in the kidney. Cephaloridine, used for comparative purposes, produced tubular necrosis of the renal cortex at one-third this dose, i.e., 100 mg/kg.