OPTIma: simplifying calorimetry for proton computed tomography in high proton flux environments.

Objective.Proton computed tomography (pCT) offers a potential route to reducing range uncertainties for proton therapy treatment planning, however the current trend towards high current spot scanning treatment systems leads to high proton fluxes which are challenging for existing systems. Here we demonstrate a novel approach to energy reconstruction, referred to as 'de-averaging', which allows individual proton energies to be recovered using only a measurement of their integrated energy without the need for spatial information from the calorimeter.Approach.The method is evaluated in the context of the Optimising Proton Therapy through Imaging (OPTIma) system which uses a simple, relatively inexpensive, scintillator-based calorimeter that reports only the integrated energy deposited by all protons within a cyclotron period, alongside a silicon strip based tracking system capable of reconstructing individual protons in a high flux environment. GEANT4 simulations have been performed to examine the performance of such a system at a modern commercial cyclotron facility using aσ≈ 10 mm beam for currents in the range 10-50 pA at the nozzle.Main results.Apart from low-density lung tissue, a discrepancy of less than 1% on the Relative Stopping Power is found for all other considered tissues when embedded within a 150 mm spherical Perspex phantom in the 10-30 pA current range, and for some tissues even up to 50 pA.Significance.By removing the need for the calorimeter system to provide spatial information, it is hoped that the de-averaging approach can facilitate clinically relevant, cost effective and less complex calorimeter systems for performing high current pCTs.

PEGylation of cationic liposomes encapsulating soluble Leishmania antigens reduces the adjuvant efficacy of liposomes in murine model.

Although there have been several attempts to develop a vaccine against leishmaniasis, no vaccine in human has been developed yet. Liposomes consisting of 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) encapsulating soluble Leishmania antigens (SLA) enhance protective immunity of SLA against Leishmania major infection in mice. However, they immobilized at the injection site because of their positive charge. To overcome the problem, shielding the surface charge with polyethylene glycol (PEGylation) was chosen in this study. Liposomal SLA consisting different concentrations of PEG (1.9%-15% mol) were prepared. BALB/c mice were immunized three times in 3 weeks intervals with different formulations. Lesion development and parasite burden in footpad and spleen were evaluated to specify the type of generated immune response and extent of protection. Th1/Th2 cytokine profiles and IgG isotypes were also analysed. The maximum protection was observed in mice immunized with Lip-SLA or pLip-SLA (1.9%) due to smaller footpad swelling, reduction in parasite load, an increase in IgG2a and IFN-γ production. Our results showed that immunization of mice with a high level of PEG (>7.5%) did not improve protective immunity of liposomal SLA. The presence of PEG, particularly more than 3.75%, is not recommended for protection against leishmaniasis.

The Role of Liposomal CpG ODN on the Course of L. major Infection in BALB/C Mice.

BACKGROUND: Historically, leishmanization is the most effective protective measure against Cutaneous Leishmaniasis (CL), CL lesion induced by leishmanization sometimes takes a long time to heal. Manipulation of leishmanization inoculums needed to induce a mild and acceptable CL lesion. The aim of this study was to explore if liposomal form of CpG ODN (Cytosin phosphate Guanin Oligodeoxynucleotides) mixed with Leishmania major would induce a milder lesion size in Balb/c mice. METHODS: This study was performed in Biotechnology Research Center, Mashhad, and Center for Research and Training in Skin Diseases and Leprosy, Tehran, Iran during 2008-2009. Different groups of BALB/c mice were subcutaneously (SC) inoculated with L. major mixed with liposomal form of CpG ODN, or L. major plus free CpG ODN, or L. major mixed with empty liposomes or L. major in PBS. The lesion onset and the size of lesion were recorded; the death rate was also monitored. RESULT: Footpad thickness was significantly (P<0.01) smaller, death rate was also significantly (P<0.05) lower in the mice received L. major mixed with liposomal CpG ODN or free CpG ODN than control groups received L. major in PBS or L. major plus liposomes, also mice which received L. major mixed with CpG ODN in soluble form showed a significantly (P<0.001) smaller lesion size than control groups. CONCLUSION: CpG ODN seems to be an appropriate immunopotentiator mixed with Leishmania stabilate in leishmanization.

Crystal habit modifications of ibuprofen and their physicomechanical characteristics.

Ibuprofen was crystallized from methanol, ethanol, isopropanol, and hexane at similar conditions. Marked differences in crystal habit of the samples obtained from these solvents were observed. The samples crystallized from methanol and ethanol had a polyhedral crystal habit, while those from hexane were needlelike. Those from isopropanol were elongated crystals. X-ray powder diffraction (XPD) and diferential scanning calorimetry (DSC) studies confirmed that these samples were structurally similar, therefore, polymorphic modifications were ruled out. The results showed that crystal habit modification had a great influence on the mechanical properties (compressibility, flow rate, and bulk density) of ibuprofen crystals. Samples obtained from methanol and ethanol exhibited the highest bulk density and the best flow rate, while those from hexane showed the lowest bulk density and the worst flow rate. The samples obtained from ethanol exhibited the best compression force/hardness profiles, and those obtained from hexane produced the softest tablets.