Nanoparticles (NPs) have a greater potential to travel through an organism via inhalation than any other larger particles, and could be more toxic due to their larger surface area and specific structural/chemical properties. The aim of this study was to evaluate in vitro biological effects of various inhalable metallic NPs (TiO2, Ag, Al, Zn, Ni). Human alveolar epithelial cells (A549) were exposed to various concentrations of NPs for 24 h. The extent of morphological damage was in the order of m-TiO2 > n-TiO2 > m-silica >> n-Ni approximately = n-Zn approximately = n-Ag approximately = n-Al and was affected in a dose-dependent manner. The extent of apoptotic damage measured with two-color flow cytometry was in the order of n-Zn > n- Ni > m-silica >> n- TiO2 > m- TiO2 > n-Al > n-Ag. The extent of apoptotic damage measured with DNA fragmentation was in the order of n-Zn approximately = m-silica > n- Ni >> m- TiO2 approximately = n- TiO2 approximately = n-Al > n-Ag, indicating no significant difference in the damages by both m-TiO2 and n-TiO2. The extents of apoptotic damages were also affected in a dose-dependent manner. Uptake of no other NPs but n-TiO2 and m-TiO2 into the cells was observed after 24 h exposure. The intracellular generation of ROS was significant with n-Zn but not with the other particles. These results demonstrated that various inhalable metallic NPs (TiO2, Ag, Al, Zn, Ni) could cause cell damages directly or indirectly. More detailed studies on the influence of size, structure, and composition of the NPs are needed to better understand their toxic mechanisms.

Summary Purpose Arterial spin labeling (ASL) is a developing magnetic resonance imaging (MRI) method for noninvasive measurement of cerebral blood flow (CBF). The purpose of this study was to evaluate the usefulness of ASL for detecting interictal temporal hypoperfusion in temporal lobe epilepsy (TLE). ASL-derived CBF measurements were compared with those derived from H215O positron emission tomography (PET). Methods 11 normal controls and 10 patients with medically intractable TLE were studied. Pulsed ASL (PASL) with quantitative imaging of perfusion using a single subtraction, second version (QUIPSS II) was performed in all subjects and H215O PET was performed in patients. Regional CBF values in the mesial and lateral temporal lobes were measured utilizing quantitative analysis of perfusion images. A perfusion asymmetry index (AI) was calculated for each region. Results In patients, mean CBF in the mesial temporal lobe was not significantly different between PASL and H215O PET, and ipsilateral mesial temporal CBF was lower than contralateral CBF with both techniques. PASL detected significant mesial temporal perfusion asymmetry agreeing with EEG laterality in four patients. H215O PET found ipsilateral interictal hypoperfusion in three. Both scans found unilateral hypoperfusion in one patient with bilateral EEG discharges. Conclusions Pulsed ASL may be a promising approach to detecting interictal hypoperfusion in TLE. This method has potential as a clinical alternative to H215O PET due to noninvasiveness and easy accessibility.

The neurofibromatosis type 2 gene-encoded protein, merlin, is related to the ERM (ezrin, radixin, and moesin) family of membrane-cytoskeleton-associated proteins. Recent studies suggest that the loss of neurofibromatosis type 2 function contributes to tumor development and metastasis. Although the cellular functions of merlin as a tumor suppressor are relatively well characterized, the cellular mechanism whereby merlin controls cell proliferation from membrane locations is still poorly understood. During our efforts to find potential merlin modulators through protein-protein interactions, we identified transactivation-responsive RNAbinding protein (TRBP) as a merlin-binding protein in a yeast two-hybrid screen. The interaction between TRBP and merlin was confirmed by glutathione S-transferase pull-down assays, co-immunoprecipitation, and co-localization experiments. The carboxyl-terminal regions of each protein were responsible for their interaction. Cells overexpressing TRBP showed enhanced cell growth in cell proliferation assays and also exhibited transformed phenotypes, such as anchorage-independent cell growth and tumor development in mouse xenografts. Merlin efficiently inhibited these oncogenic activities of TRBP in our experiments. These results provide the first clue to the functional interaction between TRBP and merlin and suggest a novel mechanism for the tumor suppressor function of merlin both in vitro and in vivo.

Compliant and persistent use of bisphosphonate decreases the risk of second hip fracture, in terms of secondary prevention.