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Functional Modulation (functional + modulation)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Structural Fabrication and Functional Modulation of Nanoparticle,Polymer Composites

ADVANCED FUNCTIONAL MATERIALS, Issue 10 2010
Hao Zhang
Abstract This review article summarizes recent progress in the fabrication methodologies and functional modulations of nanoparticle (NP),polymer composites. On the basis of the techniques of NP synthesis and surface modification, the fabrication methods of nanocomposites are highlighted; these include surface-initiated polymerization on NPs, in situ formation of NPs in polymer media, and the incorporation through covalent linkages and supramolecular assemblies. In these examples, polymers are foremost hypothesized as inert hosts that stabilize and integrate the functionalities of NPs, thus improving the macroscopic performance of NPs. Furthermore, due to the unique physicochemical properties of polymers, polymer chains are also dynamic under heating, swelling, and stretching. This creates an opportunity for modulating NP functionalities within the preformed nanocomposites, which will undoubtedly promote the developments of optoelectronic devices, optical materials, and intelligent materials. [source]

The clinical pharmacology of therapeutic monoclonal antibodies

DRUG DEVELOPMENT RESEARCH, Issue 3 2004
Lorin K. Roskos
Abstract Seventeen monoclonal antibodies are currently approved in the United States for therapeutic use in organ transplantation, percutaneous coronary intervention, prophylaxis of respiratory syncytial virus disease, rheumatoid arthritis, Crohn's disease, asthma, chronic lymphocytic leukemia, acute myeloid leukemia, non-Hodgkin's lymphoma, breast cancer, and colorectal cancer. All approved antibodies are of the IgG class. Thirteen are unconjugated intact antibodies, three are intact immunoconjugates, and one is a Fab fragment. Three of the antibodies are murine, five are chimeric, eight are humanized, and one is a fully human antibody generated by phage display technology. The antigen target and the structural and binding characteristics of the antibody determine the antibody's mechanism of action, pharmacokinetics, safety, and immunogenicity. Antibodies act through multiple mechanisms that include functional modulation of the antigen, recruitment of ADCC and CDC, and delivery of radionuclide or toxin payloads to target cells. Antibody half-life is usually governed by interaction with the FcRn receptor. In some cases, the antigen may act as a sink for antibody elimination. Safety profiles are determined by the pharmacology and tissue distribution of the target antigen, antibody isotype, the antibody payload, cytokine release, hypersensitivity reactions to xenogeneic protein, and immunogenicity. Fully human antibody technology may allow development of antibodies that have reduced risks of hypersensitivity reactions and immunogenicity, thereby enhancing safety and efficacy. The exquisite target specificity of antibodies, improvements in antibody engineering technology, and the wide availability of novel and validated therapeutic targets provide many current and future opportunities for the clinical development of therapeutic antibodies. Drug Dev. Res. 61:108,120, 2004. © 2004 Wiley-Liss, Inc. [source]

Zinc, copper and manganese enhanced keratinocyte migration through a functional modulation of keratinocyte integrins

EXPERIMENTAL DERMATOLOGY, Issue 6 2000
I. Tenaud
Abstract: The migration of keratinocytes plays an important role in the re-epithelialization of cutaneous wounds. Zinc, copper and manganese are used in vivo for their healing properties and their mechanism of action is still only partially known. Thus, they have been shown both to promote keratinocyte proliferation and to modulate integrins expression. The aim of this study was to determine if trace elements induce an increase of the migration of keratinocytes and if this effect is related to the modulation of integrins. Two independent migration assays were used to study keratinocyte migration: the scratch assay using normal human keratinocytes and the modified Boyden chamber using HaCaT cells. Inhibition studies using function-blocking antibodies directed to ,3, ,6, ,V and ,1 subunits were performed to investigate the modulator effect of trace elements on integrin function. In this way, zinc and copper gluconates increased ,3, ,V and ,1 function whereas manganese gluconate seems mainly able to modulate the function of ,3 and ,1. The stimulating effect of these trace elements on keratinocyte migration does not appear related to ,6 subunit. Thus, zinc, copper and manganese enhanced keratinocyte migration and one of the mechanisms was going through a modulation of integrin functions. [source]

Inhibition of carbachol-evoked oscillatory currents by the NO donor sodium nitroprusside in guinea-pig ileal myocytes

EXPERIMENTAL PHYSIOLOGY, Issue 4 2005
Seung-Soo Chung
The effect of sodium nitroprusside (SNP) on carbachol (CCh)-evoked inward cationic current (Icat) oscillations in guinea-pig ileal longitudinal myocytes was investigated using the whole-cell patch-clamp technique and permeabilized longitudinal muscle strips. SNP (10 ,m) completely inhibited Icat oscillations evoked by 1 ,m CCh. 1H-(1,2,4) Oxadiazole [4,3-a] quinoxaline-1-one (ODQ; 1 ,m) almost completely prevented the inhibitory effect of SNP on Icat oscillations. 8-Bromo-guanosine 3,,5,-cyclic monophosphate (8-Br-cGMP; 30 ,m) in the pipette solution completely abolished Icat oscillations. However, a pipette solution containing Rp-8-Br-cGMP (30 ,m) almost completely abolished the inhibitory effect of SNP on Icat oscillations. When the intracellular calcium concentration ([Ca2+]i) was held at a resting level using BAPTA (10 mm) and Ca2+ (4.6 ,m) in the pipette solution, CCh (1 ,m) evoked only the sustained component of Icat without any oscillations and SNP did not affect the current. A high concentration of inositol 1,4,5-trisphosphate (IP3; 30 ,m) in the patch pipette solutions significantly reduced the inhibitory effect of SNP (10 ,m) on Icat oscillations. SNP significantly inhibited the Ca2+ release evoked by either CCh or IP3 but not by caffeine in permeabilized preparations of longitudinal muscle strips. These results suggest that the inhibitory effects of SNP on Icat oscillations are mediated, in part, by functional modulation of the IP3 receptor, and not by the inhibition of cationic channels themselves or by muscarinic receptors in the plasma membrane. This inhibition seems to be mediated by an increased cGMP concentration in a protein kinase G-dependent manner. [source]

Inhalational anaesthetics and n -alcohols share a site of action in the neuronal Shaw2 Kv channel

BRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2010
Aditya Bhattacharji
Background and purpose:, Neuronal ion channels are key targets of general anaesthetics and alcohol, and binding of these drugs to pre-existing and relatively specific sites is thought to alter channel gating. However, the underlying molecular mechanisms of this action are still poorly understood. Here, we investigated the neuronal Shaw2 voltage-gated K+ (Kv) channel to ask whether the inhalational anaesthetic halothane and n -alcohols share a binding site near the activation gate of the channel. Experimental approach:, Focusing on activation gate mutations that affect channel modulation by n -alcohols, we investigated n -alcohol-sensitive and n -alcohol-resistant Kv channels heterologously expressed in Xenopus oocytes to probe the functional modulation by externally applied halothane using two-electrode voltage clamping and a gas-tight perfusion system. Key results:, Shaw2 Kv channels are reversibly inhibited by halothane in a dose-dependent and saturable manner (K0.5= 400 µM; nH= 1.2). Also, discrete mutations in the channel's S4S5 linker are sufficient to reduce or confer inhibition by halothane (Shaw2-T330L and Kv3.4-G371I/T378A respectively). Furthermore, a point mutation in the S6 segment of Shaw2 (P410A) converted the halothane-induced inhibition into halothane-induced potentiation. Lastly, the inhibition resulting from the co-application of n -butanol and halothane is consistent with the presence of overlapping binding sites for these drugs and weak binding cooperativity. Conclusions and implications:, These observations strongly support a molecular model of a general anaesthetic binding site in the Shaw2 Kv channel. This site may involve the amphiphilic interface between the S4S5 linker and the S6 segment, which plays a pivotal role in Kv channel activation. [source]