Skin chamber

Fig. 1. Microcirculation of a human colon carcinoma grown in the dorsal skin chamber in a severe-combined immunodeficient mouse. (Adapted from Leunig et al., 1992b.) Note that angiogenesis leads to formation of numerous blood vessels. Such a transparent preparation can permit noninvasive, continuous measurement of transport processes in normal and tumor tissues (Jain, 1985b). Parameters we can measure include hemodynamic (e.g., blood flow, vasomotion) metabolic (e.g., pH, p02, Ca2+) transport (e.g., permeability, diffusion, binding), and cell-cell interactions (e.g., adhesion, deformability).

In animals, accumulation of neutrophils in the peritoneal cavity after injection of a stimulus is often used as an in vivo indicator of migration (e.g., [135, 213, 337, 341, 429]). In vivo assays for human studies utilize a skin chamber that is plaeed over a portion of disrupted skin accumulation of cells in the ehamber is then quantified [15, 325]. Whereas these assays are dependent upon the migratory capabilities of the cells, they also depend upon the ability of cells to adhere to the endothelium and mechanisms for clearance of cells from these compartments. Thus these assays are not uniquely migration assays and do not give detailed information about the characteristics of cell movement. 

In other studies of the transport of macromolecules into tumor tissues. Yuan et al. measured the size of tumor vessel pores in LS174T human colon adenocarcinoma implanted in dorsal skin chambers in severe combined im-munodeficient mice [38]. They showed that tumor vascular pores could be as large as 0.4 jim in diameter [38]. Skinner et al [39] and Suzuki et al [40], as well as Hashizume et al. (who used electron microscopy) [46], in elegant work, identified structinal abnormalities in the endothelium of tumor blood vessels. These abnormahties included intercellular openings with a mean diameter of 1.7 jim (range, 0.3-4.7 jim) and transcellular holes with a mean diameter of 0.6 jim in mouse mammary carcinomas [45]. It should be noted that the effective diameter of 67-kDa serum albumin is 7.2 nm. Ohkouchi et al. used the Walker 256 solid tumor system to study the EPR effect of mitomycin C-dextran conjugates, and they confirmed a similarly increased uptake in soHd tumors [47]. 

One of the first cellular events observed after oral etretinate therapy of psoriasis was the loss of neutrophil migration from dermal capillaries to the epidermis. Oral etretinate also inhibited the migration of neutrophils out of suction blister bases into overlying skin chambers in normal patients (Dubertret etal., 1982). Topically applied etretinate at 0.1 mg/ml also inhibited neutrophil migration in this system. However, inhibition of neutrophil migration occurs in psoriasis after clearing of skin lesions, whatever the treatment used. Similarly, isotretinoin led to almost complete inhibition of neutrophil and monocyte migra-... 

Formaldehyde causes eye, upper respiratory tract, and skin irritation and is a skin sensitizer. Although sensory irritation, eg, eye irritation, has been reported at concentrations as low as 0.1 ppm in uncontrolled studies, significant eye/nose/throat irritation does not generally occur until concentrations of 1 ppm, based on controlled human chamber studies. Odor detection has commonly been reported to occur in the range of 0.06—0.5 ppm (133—135). 

More recent publications on sulfosuccinates have confirmed the minimal or close to zero skin and eye irritation caused by these products. In a general screening of product safety evaluation methods the authors [16] rejected the sulfosuccinate from further consideration in the statistical analysis of experimental data (variance analysis) because the product had not shown any irritation in the Duhring-Chamber test. The sulfosuccinate (based on fatty alcohol ethoxy late) was tested in a screening with 14 other surfactants, namely, alkyl sulfates, sulfonates, ether sulfates, and a protein fatty acid condensation product. 

In a broad evaluation also the sulfosuccinate disodium laureth sulfosuccinate (DLSS) was a part of a variety of surfactants tested for their dermatological mildness, and some different test methods were applied [16]. Products were compared applying in vitro methods (Zein test, hemolysis) and in vivo methods (Duhring-Chamber test, skin mildness by intracutaneous test on mice and topical application on hairless mice, mucous membrane irritation according to the Draize procedure on rabbit eyes). In the Duhring-Chamber test the DLSS elicited no reactions in the animal tests it ranged in the least irritant third of the 15 products tested. 

Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections. Clin Infect Dis 2005 41 1373-1406. 

It should be noted that HCN can be absorbed through the skin. For this reason, ACGIH (1996) and NIOSH (1997) guidelines carry a skin notation. Drinker (1931) cites the case of three men protected with gas masks in an atmosphere of 2% (20,000 ppm) HCN. After 8 or 10 min the men felt symptoms of marked dizziness, weakness, and throbbing pulse. They left the chamber just before collapse. For several hours after the exposure they experienced weakness, high pulse rate, and headache. They were incapacitated for several days, followed by complete recovery. Based on exposure to several cyanide salts, the dermal LD50 in rabbits was calculated to be 6.7 mg CN/kg (Ballantyne 1983). 

The specific mechanism by which mirex is transferred from the gut, lungs, or skin to the blood is not known. However, mirex is a highly stable, lipophilic compound that is resistant to metabolism. It has a high lipid water partition coefficient (HSDB 1994a, 1994b), so it partitions readily to fat and demonstrates a very high potential for accumulation in tissues (Chambers et al. 1982 Ivie et al. 1974b). 

Dosing is possible in infinite (typically >10 /xl/cm2 or 10 mg/cm2) or finite manner (<10 /xl/cm2 or 10 mg/cm2). The donor chamber may either be left open or be occluded. Nonoccluded conditions permit an exchange with the environment, such as evaporation of volatile substances and drying of the skin surface. In contrast, a tight occlusion of the skin surface may lead to excessive... 

While Franz-type diffusion cells are commonly used to assess in vitro penetration of compounds across the skin, they have also been used for the assessment of compound permeability across the buccal mucosa [19, 71, 104], In this system, buccal mucosa is sandwiched between two chambers, and compound solution is added to the donor chamber with compound-free buffer in the receptor chamber. The receptor chamber is then periodically sampled to assess the amount of compound that has permeated the tissue over time. 

Potassium cyanide (KCN) is a white crystalline substance with a slight odor of bitter almonds. It is produced when hydrogen cyanide is absorbed in potassium hydroxide. It is used to extract gold and silver from their ores, in electroplating computer boards, and as an insecticide. Potassium cyanide is very toxic to the skin or when ingested or inhaled, and it is used as a source of cyanide (CN) gas in gas chambers. 

It is well recognized that in vitro angiogenesis assays can have clear advantages. However, the major drawback of all of these assays is that they require the endothelial cells to be removed from their natural microenvironment, which alters their physiological properties. To study angiogenesis in vivo, the most frequently used assay systems exploit chicken chorio-allanto-ic membrane (CAM) [28,60], the corneal pocket [61], transparent chamber preparations such as the dorsal skin fold chamber [62,63], the cheek pouch window [64] and polymer matrix implants [65,66]. 

Implantation of polymer matrices that contain angiogenic factors requires quantification of the extent of vessel ingrowth. This can either be analysed immunohistochemically or by haemoglobin/red blood cell count in the tissue. These models generally do not allow analysis of the time course of vascularization since this would require the sacrifice of animals. Application in a dorsal skin fold chamber circumvents this experimental problem, as it provides the opportunity to monitor vessel formation at various time points during the experiment. 

OECD has adopted an in vitro test for skin absorption potential (OECD TG 428, Skin Absorption In Vitro Method). According to this guideline, excised skin from human or animal sources can be used. The skin is positioned in a diffusion cell consisting of a donor chamber and a receptor chamber, between the two chambers. The test substance, which may be radio-labeled, is applied to the surface of the skin sample. The chemical remains on the skin for a specified time under specified conditions, before removal by an appropriate cleansing procedure. The fluid in the receptor chamber is sampled at time points throughout the experiment and analyzed for the test chemical and/or metabolites. 

The article describes the process of producing expanded polypropylene foam parts with a solid integral skin on one side, citing a bicycle helmet moulded from BASF s Neopolen EPP bead, as an illustration. The self-skinning EPP process reqnires some modification of standard beadmoulding equipment, needing an extra steam chamber. Automotive interior trim is a potential application for the process. 

Between 1958 and 1972, 99 human subjects underwent experimental exposures to CN at Edgewood Arsenal. Sixty-nine subjects had aerosol exposures in a chamber that they entered masked they removed the masks after the agent concentration had equilibrated. Thirty subjects had direct skin applications of CN. 

Kangesu T, Navsaria HA, Manek S, Shurey CB, Jones CR, Fryer PR, Leigh IM, Green CJ (1993) A porcine model using skin graft chambers for studies on cultured keratinocytes. Br J... 

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