Titanium dioxide nanoparticles (nanoTiO2) have been widely used as a photocatalyst in air and water cleaning. However, these nanoparticles inhalation can induce pulmonary toxicity and its mechanism is not fully understood. In this study we investigated the pulmonary toxicity of nanoTiO2 and its molecular pathogenesis. The adult male ICR mice were exposed to intratracheal single dose of 0.1 or 0.5 mg nanoTiO2 (19-21 nm) and lung tissues were collected at 3rd day, 1st wk, and 2nd wk for morphometric, microarray gene expression, and pathway analyses. NanoTiO2 can induce pulmonary emphysema, macrophages accumulation, extensive disruption of alveolar septa, type II pneumocyte hyperplasia, and epithelial cell apoptosis. NanoTiO2 induced differential expression of hundreds of genes include activation of pathways involved in cell cycle, apoptosis, chemokines, and complement cascades. In particular, nanoTiO2 up-regulates placenta growth factor (PlGF) and other chemokines (CXCL1, CXCL5, and CCL3) expressions that may cause pulmonary emphysema and alveolar epithelial cell apoptosis. Cultured human THP-1 cell-derived macrophages treated with nanoTiO2 in vitro also resulted in up-regulations of PlGF, CXCL1, CXCL5, and CCL3. These results indicated that nanoTiO2 can induce severe pulmonary emphysema, which may be caused by activation of PlGF and related inflammatory pathways.

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Yang C-C, Chien C-T, Wu M-H, Ma M-C, Chen C-F. NMDA receptor blocker ameliorates ischemia-reperfusion-induced renal dysfunction in rat kidneys. Am J Physiol Renal Physiol 294: F1433-F1440, 2008. First published February 13, 2008 doi:10.1152 doi:10. /ajprenal.00481.2007 receptor activated by glutamate/glycine is located in the kidneys. The NMDA receptor subunit NR1 is increased in damaged renal tissue. This study explored the role of NMDA receptors in ischemiareperfusion-induced renal dysfunction in rats. With Western blot analysis and renal functional assay, NMDA receptor expression was evaluated, as well as its functional role in female Wistar rat kidneys after 45 min of unilateral ischemia followed by 24 h of reperfusion. The effects of intrarenal NMDA receptor agonist and antagonist on renal blood flow (RBF), glomerular filtration rate (GFR), urine volume (UV), sodium (U NaV), and potassium (UKV) excretion were determined. NMDA NR1 was present in the glomeruli, brush-border membrane, and outer medulla but not in the cortex and inner medulla. Homogenous distribution of non-NMDA GluR2/3, sparse kainate KA1, and undetectable group I of metabotropic glutamate receptor were noted in the control kidneys. Ischemia-reperfusion kidneys showed enhanced renal NR1, but not NR2C and GluR2/3 expression, and were associated with decreased GFR/RBF and natriuretic/diuretic responses. Intrarenal NMDA agonists significantly reduced GFR, UV, U NaV, and UKV but had no effect on blood pressure and RBF in sham control and ischemia-reperfusion kidneys. NMDA antagonist D-2-amino-5-phosphonopentanoic acid (D-AP-5) treatment completely abolished NMDA-induced renal dysfunction. D-AP-5 treatment significantly ameliorated ischemia-reperfusion-induced glomerular and tubular dysfunction by restoring decreased GFR, UV, and U NaV levels. Ischemia-reperfusion upregulates renal NMDA NR1 receptor expression, leading to reduced glomerular and tubular function in the kidneys. The NMDA antagonist can ameliorate ischemia-reperfusioninduced renal dysfunction.ischemia-reperfusion; kidney; glutamate; renal function GLUTAMATE HAS BEEN CHARACTERIZED as an excitatory neurotransmitter in the mammalian central nervous system. It could bind to ionotropic (iGluR) and metabotropic (mGluR) glutamate receptors to mediate synaptic transmission and integrity (7, 37). The iGluR, including N-methyl-D-aspartate (NMDA) and non-NMDA, such as ␣-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA)/kainate, receptors, function as calcium channel membranes, and their activation results in an influx of intracellular calcium (17,38,39,42,43). This leads to neuronal cell death by calcium toxicity or by the activation of calcium-dependent type I nitric oxide synthase (NOS-I) (5, 16). Among these functions are the suppression of peripheral sympathetic reflex discharges (28, 37) and cerebral vasodilatation (49).The NMDA receptor is composed of various subunits, including NR1, NR2A, NR2B, NR2C, and NR2D (2, 24, 29). The NR1 subunit is the main subunit of the NMDA receptor (2,...

Objective: To study postnatal cardiac differentiation in the mouse. Hypothesis: There might be mechanisms or factors in cardiac differentiation that could be identified by systematic gene expression analysis during postnatal cardiac development. Methods: Expression of 6144 genes was examined in mouse heart, from the newborn period (day 0), through day 7 and day 14 day, to adulthood, using the cDNA microarray approach. Northern blotting and immunohistochemical techniques were used to confirm the microarray results. Results: Various cardiac development related genes involving the cell cycle (cyclin B1, proliferating cell nuclear antigen (PCNA), and Ki67), growth factors (IGF-II, pleiotrophin (PTN), and midkine (MK)), and transcriptional regulation, cytoskeleton, and detoxification enzymes were identified by microarray analysis. Some of these genes were also confirmed by Northern blotting and immunohistochemistry of their RNA and protein content. In vivo treatment with PTN (20 ng/g) increased bromodeoxyuridine incorporation (by 2.24-fold) and PCNA expression (by 1.71-fold) during day 7 to day 14, indicating that PTN induces cell proliferation in mouse heart. Conclusions: Global gene expression analysis in the whole heart may be useful in understanding the orchestrated process of postnatal development or terminal differentiation in the cardiac environment. These data are likely to be helpful in studying developmental anomalies of the heart in neonates

Small-dose propofol sedation, compared with IV midazolam, attenuates free radical production after release of the tourniquet during total knee replacement under spinal anesthesia.