Local tissue response

In summary, preliminary results from two animal models (rabbit and mouse) indicate that poly(N-palmitoylhydroxyproline ester) elicits a very mild, local tissue response that compares favorably with the responses observed for established biomaterials such as medical grade stainless steel or poly(lactic acid)/poly(glycolic acid) implants. At this point, additional assays need to be performed to evaluate possible allergic responses, as well as systemic toxic effects, carcinogenic, teratogenic, or mutagenic activity, and adaptive responses. 

In order to influence mast-cell function, peptides must be made available at sites very near to tissue mast cells. One means of accomplishing this is by specific peptidergic innervation. This would not necessarily require a classical synaptic morphology, but only the termination of nerves within the vicinity of mast cells [1,3]. Modulation of mast-cell secretion by peptides of neural origin is particularly attractive, for it would allow for a restricted, localized expression of peptide action in specific target tissues because of the selective distribution of each peptide within particular neurones. Moreover, this could be further modified and restricted by differing mast cell specificities. (Heterogeneity of mast cell responsiveness to peptide stimulation has been well documented [52, 53 ].) The result would permit a well-localized tissue response without systemic manifestation [3]. 

The sensitivity to irritation is different for different tissues in the body. Biocompatibility is therefore highly related to the injection site. For instance, the rabbit eye is a highly sensitive animal model for biocompatibility studies [82, 83]. Surface topography is another important parameter of biocompatibility [79]. Sharp edges or corners may cause irritation and enhance the local tissue response [40]. 

Spector M, Cease C, and Tongi-Li X (1989) The local tissue response to biomaterials. Clinical Reviews in Biocompatibility 5 269-295. 

THE NATURE AND MECHANISM OF INFLAMMATION Inflammation may be defined as a series of localized tissue responses to foreign stimuli, which may be biological (e.g. bacteria, fungi, viruses), chemical (e.g. croton oil) or physical (e.g. X-rays, ultra-violet light). Apart from external stimuli, it now appears than an endogenous factor, the autoimmune reaction, may initiate an inflammatory response. 

In most cases the painful localized tissue response will resolve in a few hours without therapy. Some symptomatic relief may be obtained by topical application of ice, papain (meat tenderizer), or creams containing corticosteroids or antihistamines. 

An edited collection of contributions dealing with the major components of biocompatibility mechanisms, including corrosion and degradation phenomena, toxicology and the local tissue response. 

Rock, M.G. and Hardie, R. (1988) Analysis of local tissue response in 50 revision total hip arthroplasty patients. Trans. Soc. Biomater., XI, 43. 

The significant advance of these beads is the demonstration of an effective process for consistent drug release that controls local tissue response. Recent animal studies on a model of liver cancer have confirmed the in vivo slow release of doxorubicin overtime within the tumor, with maintenance of a high concentration of drug for up to 14 days. Pharmacokinetic data of this study showed near complete absence of doxorubicin within plasma, while intratumoral doxorubicin concentrations remained high [22]. 

The likelihood that materials will produce local effects in the respiratory tract depends on their physical and chemical properties, solubiHty, reactivity with fluid-lining layers of the respiratory tract, reactivity with local tissue components, and (in the case of particulates) the site of deposition. Depending on the nature of the material, and the conditions of the exposure, the types of local response produced include acute inflammation and damage, chronic... 

Arthus reaction Local inflammatory response due to deposition of immune complexes in tissues. 

Length and size of CNTs seriously affect their cytotoxicities (Sato et al., 2005 Cui et al., 2007). CNTs of 825 nm in length caused stronger inflammation in human acute monocytic leukemia cell line THP-1 than CNTs of 220 nm in length, as shown in Fig. 9.5. However, histological observation as shown in Fig. 9.6, showed that no severe inflammatory response such as necrosis, white cells aggregates, etc. This result indirectly shows that CNTs can cause noninflammatory damage to local tissues. 

Calu-3 cells have shown the ability to perform fatty acid esterification of budes-onide [132], In pre-clinical studies, this esterification results in a prolonged local tissue binding and efficacy, which is not found when the esterification is inhibited [133]. The precise mechanism remains undefined in that the identity of specific enzyme(s) responsible for this metabolic reaction is unclear [134], Assessment of the potential toxicity and metabolism of pharmaceuticals and other xenobiotics using in vitro respiratory models is still at its infancy. The development of robust in vitro human models (i.e., cell lines from human pulmonary origin) has the potential to contribute significantly to better understanding the role of biotransformation enzymes in the bioactivation/detoxication processes in the lung. 

Histamine contributes to the progression of allergic-inflammatory responses by enhancement of the secretion of proinflammatory cytokines like IL-la, IL-1(3, IL-6 as well as chemokines like RANTES or IL-8, both in several cell types and local tissues [26-29]. Endothelial cells express functional HRl and HR2 and increased adhesion molecule expression such as ICAM-1, VCAM-1 and P-selectin was demonstrated by histamine infusion via HRl [30-32]. Histamine regulates the expression of its own receptors on endothelial cells and influences the overall inflammatory reaction [33]. 

Host cells are killed by cytotoxic T-ceUs or natural kiUer cells by the processes of necrosis or apoptosis. Necrosis leads to release of cell contents that can sufficiently disturb the tissue to initiate a local inflammatory response. However, the cell killed by apoptosis is then phagocytosed, which does not cause local disturbance, so that inflammation does not occur (Chapter 20). Apoptosis is achieved by two mechanisms release of toxic granules by the cytotoxic cells or by the binding of the cytotoxic ceU to the host ceU, via its death receptor protein (see below). 

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