Significant Inhibition of Tumor Growth following Single Dose Nanoparticle-Enhanced Photodynamic Therapy

Photodynamic therapy (PDT) for cancer treatment involves the pathology’s uptake of photosensitizers, which produce cytotoxic reactive oxygen species by photoirradiation. The use of nanoparticles as carriers of photosensitizers is one promising approach to this endeavor, owing to their small size, unique physicochemical properties, and easy/diverse functionalization. In the current work, we report on the in vivo assessment of PDT efficacy of these nanoconstructs in a murine model of human breast cancer, following a single (one-shot) nanoparticle dose and photoirradiation. Palladium-porphyrin (PdTPP) was administered intratumorally via injection of aqueous suspensions of either free PdTPP or MSN-conjugated PdTPP (MSN-PdTPP) at a dose of 50 μg. Mice were then exposed to a single photoirradiation session with total energy of 80 J. One month after one-shot PDT treatment, significantly greater reductions in tumor growth were observed in MSN-Pd treated animals than in PdTPP cohorts. Electron microscopy of tumor specimens harvested at various timepoints revealed excellent MSN-PdTPP uptake by cancer cells while immunohistologic analysis demonstrated marked increases in apoptotic response of MSN-PdTPP treated animals relative to PdTPP controls. Taken together, these findings suggest that considerable improvements in PDT efficacy can readily be achieved via the use of nanoparticle-based photosensitizers

Tc-99m pyrophosphate imaging of poloxamer-treated electroporated skeletal muscle in an in vivo rat model

Objective: This study investigates whether 99mTc pyrophosphate (PYP) imaging provides a quantitative non-invasive assessment of the extent of electroporation injury, and of the effect of poloxamer in vivo on electroporated skeletal muscle. Methods: High-voltage electrical shock was used to produce electroporation injury in an anesthetized rat\u27s hind limb. In each experiment, the injured limb was treated intravenously by either poloxamer-188, dextran, or saline, and subsequently imaged with 99mTc PYP. The radiotracer\u27s temporal behavior among the experimental groups was compared using curve fitting of time-activity curves from the dynamic image data. Results: The washout kinetics of 99mTc PYP changed in proportion to the electric current magnitude that produced electroporation. Also, 99mTc PYP washout from electroporated muscle differed between poloxamer-188 treatment and saline treatment. Finally, 10-kDa dextran treatment of electroporated muscle altered 99mTc PYP washout less than poloxamer-188 treatment. Conclusions: Behavior of 99mTc PYP in electroporated muscle appears to be an indicator of the amount of electroporation injury. Compared to saline, intravenous polaxamer-188 treatment reduced the amount of 99mTc PYP uptake. Coupled to results showing poloxamer-188 seals ruptured cellular membranes, lessens the extent of electroporation injury and improves cell viability, 99mTc PYP imaging appears to be a useful in vivo monitoring tool for the extent of electroporation injury. © 2006 Elsevier Ltd and ISBI

Contralateral versus ipsilateral protective effect against muscle damage of the elbow flexors and knee extensors induced by maximal eccentric exercise

The present study compared the ipsilateral repeated bout effect (IL-RBE) and contralateral repeated bout effect (CL-RBE) of the elbow flexors (EF) and knee flexors (KF) for the same interval between bouts to shed light on their mechanisms. Fifty-two healthy sedentary young (20–28 years) men were randomly assigned to the IL-EF, IL-KF, CL-EF, and CL-KF groups (n = 13/group). Thirty maximal eccentric contractions of the EF were performed in IL-EF and CL-EF, and 60 maximal eccentric contractions of the KF were performed in IL-KF and CL-KF, with a 2-week interval between bouts. Changes in muscle damage markers such as maximal voluntary contraction (MVC) torque, muscle soreness, and plasma creatine kinase activity, and proprioception measures before to 5 days post-exercise were compared between groups. Changes in all variables were greater (p \u3c 0.05) after the first than second bout for all groups, and the changes were greater (p \u3c 0.05) for the EF than KF. The changes in all variables after the second bout were greater (p \u3c 0.05) for the CL than IL condition for both EF and KF. The magnitude of the average protective effect was similar between CL-EF (33%) and CL-KF (32%), but slightly greater (p \u3c 0.05) for IL-EF (67%) than IL-KF (61%). These demonstrate that the magnitude of CL-RBE relative to IL-RBE was similar between the EF and KF (approximately 50%), regardless of the greater muscle damage for the EF than KF. It appears that the CL-RBE is more associated with neural adaptations at cerebrum, cerebellum, interhemispheric inhibition, and coricospinal tract, but the IL-RBE is induced by additional adaptations at muscles

Genetic analysis of fish iridoviruses isolated in Taiwan during 2001–2009

To investigate the genetic relationships between field strains of iridoviruses gathered from various fish species in Taiwan, viruses that were collected from 2001 to 2009 were analyzed. Open reading frames encoding the viral major capsid protein (MCP) and adenosine triphosphatase (ATPase) were sequenced for phylogenetic analysis. Our results indicated that iridoviruses from Taiwan aquaculture fishes could be classified into two groups: prior to 2005, the viruses were closely related to members of the genus Ranavirus; and after 2005, they were similar to members of the genus Megalocytivirus. Based on the analysis of MCP amino acid sequences, virus isolates were divided into 4 major genotypes that were related to ISKNV, RSIV, FLIV, and GIV, respectively. Pairwise comparisons of MCP genes showed that the ranavirus was an epidemic pathogen for economically important species in the major production regions and cultured marine fish, while the megalocytivirus isolates were sensitive to host range. In addition, the distribution of synonymous and non-synonymous changes in the MCP gene revealed that the iridoviruses were evolving slowly, and most of the variations were synonymous mutations. The Ka/Ks values were lower than one, and hence, the viruses were under negative selection

The ‘Singapore Fever’ in China: policy mobility and mutation

The ‘Singapore Model’ has constituted the only second explicit attempt by the Communist Party of China (CPC) to learn from a foreign country following Mao Zedong’s pledge to contour ‘China’s tomorrow’ on the Soviet Union experience during the early 1950s. This paper critically evaluates policy transfers from Singapore to China in the post-Mao era. It re-examines how this Sino-Singaporean regulatory engagement came about historically following Deng Xiaoping’s visit to Singapore in 1978, and offers a careful re-reading of the degree to which actual policy borrowing by China could transcend different state ideologies, abstract ideas and subjective attitudes. Particular focus is placed on the effects of CPC cadre training in Singapore universities and policy mutation within two government-to-government projects, namely the Suzhou Industrial Park and the Tianjin Eco-City. The paper concludes that the ‘Singapore Model’, as applied in post-Mao China, casts institutional reforms as an open-ended process of policy experimentation and adaptation that is fraught with tension and resistance

Aerosolized In Vivo 3D Localization of Nose-to-Brain Nanocarrier Delivery Using Multimodality Neuroimaging in a Rat Model—Protocol Development

The fate of intranasal aerosolized radiolabeled polymeric micellar nanoparticles (LPNPs) was tracked with positron emission tomography/computer tomography (PET/CT) imaging in a rat model to measure nose-to-brain delivery. A quantitative temporal and spatial testing protocol for new radio-nanotheranostic agents was sought in vivo. LPNPs labeled with a zirconium 89 (89Zr) PET tracer were administered via intranasal or intravenous delivery, followed by serial PET/CT imaging. After 2 h of continuous imaging, the animals were sacrificed, and the brain substructures (olfactory bulb, forebrain, and brainstem) were isolated. The activity in each brain region was measured for comparison with the corresponding PET/CT region of interest via activity measurements. Serial imaging of the LPNPs (100 nm PLA–PEG–DSPE+89Zr) delivered intranasally via nasal tubing demonstrated increased activity in the brain after 1 and 2 h following intranasal drug delivery (INDD) compared to intravenous administration, which correlated with ex vivo gamma counting and autoradiography. Although assessment of delivery from nose to brain is a promising approach, the technology has several limitations that require further development. An experimental protocol for aerosolized intranasal delivery is presented herein, which may provide a platform for better targeting the olfactory epithelium