This is the first of three papers in which the kinetics of formation of chemically bonded phosphate ceramics is discussed. A literature survey indicates that the formation of such ceramics is a three‐step process. First, oxides dissolve in a phosphoric acid or an acid phosphate solution and metal ions are released into the solution. The aquoions formed from these cations then react with phosphate anions and form a gel of metal hydrophosphates. In the last step, the saturated gel crystallizes into a ceramic. In this paper, we have proposed that the dissolution is the controlling step and developed a general dissolution model of the kinetics of formation of these ceramics. As an example, the model is used to discuss the kinetics of formation of magnesium phosphate ceramics in detail. In the second and third papers, the model has been used to develop processes to form ceramics of alumina and iron oxides.

Oxidative stress is implicated in the pathogenesis of allergic asthma and remains an attractive target for the prevention of the disease. Herein, we investigated the anti-inflammatory effects of apocynin, a NADPH oxidase (NOX) inhibitor, in both in vitro and in vivo allergen-induced experimental asthma mediated by Th2 hyperresponsiveness. Apocynin showed potential antioxidant activities and inhibitory effects on the activation of redox-sensitive transcription factors, such as NF-jB and AP-1, induced by pro-inflammatory stimuli, such as TNF-a, lipopolysaccharide and Poly I:C, and that inhibited the production of pro-inflammatory cytokines, such as TNF-a, IL-1b and IL-6. In in vivo experimental asthma model, moreover, apocynin significantly attenuated ovalbumin-induced airway hyperresponsiveness and inflammation, as shown by the attenuation of total inflammatory cell and soluble product influx into bronchoalveolar lavage fluid, such as macrophages, eosinophils, IL-4, IL-5, IL-12, IL-13 and TNF-a. Apocynin also significantly reduced lung inflammation in the tissues. Altogether, these results suggest that apocynin may be useful in the treatment of inflammatory diseases induced by oxidative stress through NOX activity. Keywords: apocynin; NADPH oxidase; oxidative stress; asthma; inflammation; NF-kB Asthma is a chronic inflammatory lung disease characterized by infiltration of inflammatory cells, including eosinophils, and airway hyperresponsiveness (AHR). 1-5 T-helper type 2 (Th2) cells, together with other inflammatory cells such as macrophages, eosinophils, mast cells and B cells, have critical roles in the initiation, development and chronicity of this disease. 1 Upon challenge with various allergens, these inflammatory cells infiltrate into the airway and contribute to the production of Th2 cytokines, such as IL-4, IL-5 and IL-13, which are found at elevated levels in asthmatic lungs. 1-5 Th2 cytokines are pivotal for B cell maturation, IgR synthesis, airway eosinophilia, mucus secretion and ultimately AHR. Specifically, IL-4 regulates allergic inflammation by promoting Th2 cell differentiation, controlling the production of IgE in B cells, stimulating B cell proliferation, inducing the upregulation of MHC class II molecules and increasing the expression of an inducible form of the low-affinity receptor for IgE (FcRII or CD23) on B lymphocytes and macrophages. 4,5 IL-5 influences the production, maturation and activation of eosinophils. 4,5 IL-13 is a potent modulator of human monocyte and B cell function. 5 IL-13 is also capable of inducing the expression of CD23 on purified human B cells and acts as a switch factor directing IgE synthesis. 5 Increased reactive oxygen species (ROS) generation, which results in imbalance between oxidative forces and the antioxidant defense systems, has been implicated in the pathogenesis of asthma. 6-8 ROS are capable of eliciting a variety of pathological changes, including the peroxidation of lipids, proteins and DNA, and the generation of chemo-attractants, enhancement of AHR,...

Although previous studies have proposed plausible mechanisms of the activation of transforming growth factor-β-activated kinase 1 (TAK1) in inflammatory signals, including Toll-like receptors (TLRs), its activating kinase still remains to be unclear. In the present study, we have provided evidences that AMP-activated protein kinase (AMPK)-α1 has a pivotal role for activating TAK1, and thereby regulate NF-κB-dependent gene expressions in inflammatory signaling mediated by TLR4 and TNF-α stimulation. AMPK-α1 specifically interacts with TAK1 and reciprocally regulates their kinase activities. Upon the stimulation of lipopolysaccharide, AMPK-α1-knockdown (AMPK-α1KD) or TAK1-knockdown human monocytic THP-1 cells exhibit a dramatic reduction in the TAK1 or AMPK-α1 kinase activity, respectively, and subsequent suppressions of its downstream signaling cascades, which further leads to inhibitions of NF-κB and thereby productions of proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6. Importantly, the microarray analysis of AMPK-α1KD cells revealed a dramatic reduction in the NF-κB-dependent genes induced by TLR4 and TNF-α stimulation, and the observation was in significant correlation with the results of quantitative real-time PCR. Moreover, AMPK-α1KD cells are highly sensitive to the TNF-α-induced apoptosis, which is accompanied with dramatic reductions in the NF-κB-dependent and anti-apoptotic genes. As a result, our data demonstrate that AMPK-α1 as an activating kinase of TAK1 has a key role in mediating inflammatory signals triggered by TLR4 and TNF-α.