Temperature regulation and heat dissipation during flight in birds.
(1/1118)
Core and skin temperature were measured by radiotelemetry in starlings (Sturnus vulgaris) during 30 min flights in a wind tunnel. Core temperature was independent of ambient temperature from 0 to 28 degrees C. The temporal mean of the monitored core temperature during flight was 42-7 degrees C in one bird and 44-0 degrees C in another. These temperatures are 2-4 degrees C higher than the resting temperature in starlings, and are among the highest steady-state temperatures observed in any animal. Skin temperature on the breast was within a few degrees of core temperature. In some locations skin temperature was higher at low ambient temperatures than at intermediate ambient temperatures. An analysis of the data shows that a high core temperature does not function as an aid to head dissipation. On the contrary, insulation is adjusted to maintain a high temperature, presumably because it is necessary for flight. The increase in skin temperature at low ambient temperatures is believed to be a result of a decrease in heat flow through the breast feathers brought about by feather adjustments, to compensate for an unavoidable increase in heat flow in unfeathered or poorly feathered parts of the body. (+info)
Topical gene delivery to murine skin.
(2/1118)
We topically applied naked plasmid DNA containing the luciferase or chloramphenicol acetyltransferase cDNA directly to mouse skin. Gene expression was detected in skin samples as early as 4 h after DNA application, plateaued from 16 to 72 h post-application, and had decreased significantly by 7 d post-application. Reporter gene activity following topical DNA delivery was comparable with that produced by intradermal injection of DNA. Plasmid DNA at concentrations > or =0.25 microg per microl were required to achieve maximal expression levels. Reporter gene expression following topical administration was largely confined to the superficial layers of the epidermis and to hair follicles. Surprisingly, certain cationic liposomes inhibited the efficiency of cutaneous gene transfer. This technique provides a simple, clinically relevant approach to deliver genes to the skin, with potential application in treating a variety of cutaneous disorders. (+info)
UVA exposure of human skin reconstructed in vitro induces apoptosis of dermal fibroblasts: subsequent connective tissue repair and implications in photoaging.
(3/1118)
The skin reconstructed in vitro has been previously shown to be a useful model to investigate the effects of UVB exposure (Bernerd and Asselineau, 1997). The present study describes the response to UVA irradiation. Major alterations were observed within the dermal compartment. Apoptosis of fibroblasts located in the superficial area of the dermal equivalent was observed as soon as 6 h after irradiation, leading to their disappearance after 48 h. This effect was obtained without major alterations of epidermal keratinocytes suggesting a differential cell type sensitivity to UVA radiations. In addition, collagenase I was secreted by dermal fibroblasts. The UVA dermal effects could be observed even after removal of the epidermis during the post irradiation period, demonstrating that they were independent of the keratinocyte response. The analysis of the tissue regeneration during the following 2 weeks revealed a connective tissue repair via fibroblasts proliferation, migration and active synthesis of extracellular matrix proteins such as fibronectin and procollagen I. This cellular recolonization of the superficial part of the dermal equivalent was due to activation of surviving fibroblasts located deeply in the dermal equivalent. The direct damage in the dermis and the subsequent connective tissue repair may contribute to the formation of UVA-induced dermal alterations. (+info)
Time-dependent ultrastructural changes to porcine stratum corneum following an electric pulse.
(4/1118)
The morphological changes to heat-stripped porcine stratum corneum following an electroporating pulse were studied by time-resolved freeze fracture electron microscopy. Pulses at a supra-electroporation threshold of 80 volts and 300 microseconds were applied across the stratum corneum with a pair of copper plate electrodes, which also served as cooling contacts. Multilamellar vesicles of 0.1-5.5 mm in diameter in the intercellular lipid bilayers of the stratum corneum appeared in less than milliseconds after pulsing. Pulsed samples exhibited aggregations of vesicles, whereas only occasional single vesicles were seen in the unpulsed samples. Aggregates form in less than a millisecond and disappear within minutes after the pulse. Their size ranged from 0.3 to 700 mm2. The size of individual vesicles, aggregate density, and size were analyzed as functions of postpulse time. These aggregate formations seem to be a secondary reaction to the pulse-induced skin permeabilization, determined by the resistance drop and recovery after the pulse. Heating the samples to 65 degrees C also caused vesicle aggregates of similar appearance to form, suggesting that these aggregations are related to the heating effect of the pulse. Hydration is thought to play an important role in aggregate formation. (+info)
Keratinocyte growth regulation in fibroblast cocultures via a double paracrine mechanism.
(5/1118)
Epithelial-mesenchymal interactions play an important role in regulating tissue homeostasis and repair. For skin, the regulatory mechanisms of epidermal-dermal interactions were studied in cocultures of normal human epidermal keratinocytes (NEK) and dermal fibroblasts (HDF) rendered postmitotic by alpha-irradiation (HDFi). The expression kinetics of different cytokines and their receptors with presumed signalling function in skin were determined at the RNA and protein level in mono- and cocultured NEK and HDFi. In cocultured HDFi, mRNA and protein synthesis of keratinocyte growth factor (KGF) (FGF-7) was strongly enhanced, whereas in cocultured keratinocytes interleukin (IL)-1alpha and -1beta mRNA expression increased compared to monocultures. Thus we postulated that IL-1, which had no effect on keratinocyte proliferation, induced in fibroblasts the expression of factors stimulating keratinocyte proliferation, such as KGF. The functional significance of this reciprocal modulation was substantiated by blocking experiments. Both IL-1alpha and -1beta-neutralizing antibodies and IL-1 receptor antagonist significantly reduced keratinocyte proliferation supposedly through abrogation of KGF production, because IL-1 antibodies blocked the induced KGF production. These data indicate a regulation of keratinocyte growth by a double paracrine mechanism through release of IL-1 which induces KGF in cocultured fibroblasts. Thus IL-1, in addition to its proinflammatory function in skin, may play an essential role in regulating tissue homeostasis. (+info)
Injection of pre-psoriatic skin with CD4+ T cells induces psoriasis.
(6/1118)
Psoriasis is an immunologically mediated skin disease linked to several different class I major histocompatibility complex alleles. However, the phenotype of the pathogenic lymphocyte and nature of the T cell activating event which triggers conversion of symptomless (PN) skin into psoriatic plaques (PP skin) is unknown. This study extends our previous observations in which autologous blood-derived immunocytes were injected into PN skin engrafted onto SCID mice to produce full-fledged PP lesions. The first question addressed is whether injected CD4+ T cells or CD8+ T cells were responsible for phenotypic conversion of PN to PP skin. In five different patients only CD4+ but not CD8+ T cell lines produced psoriatic lesions. Next, immunological events occurring within PN skin following injection of CD4+ T cells in grafts that had sufficient tissue available for detailed analysis was examined. In two patients, intraepidermal resident CD8+ T cells were induced to proliferate during lesion development, expressing acute activation markers CD25 and CD69. In another patient, injection of CD4+ T cells revealed CD69 expression by intraepidermal CD4+ as well as CD8+ T cells. To explore the molecular basis for local T cell activation and proliferation, we discovered that intraepidermal immunocytes, including both CD4 and CD8+ T cells, expressed surface receptors (ie, CD94, CD158a, CD158b) typically confined to natural killer cells (ie, natural killer receptors; NKRs) accumulated immediately before onset of acute lesions. The presence of NKR bearing immunocytes was also observed in 10 of 15 different biopsies of chronic plaques taken directly from patients, whereas PN skin (n = 8) or normal skin from healthy donors (n = 8), did not contain such NKR positive immunocytes. Of particular relevance to psoriasis is that these NKRs recognize various class I alleles including those typically inherited by psoriatic family members such as HLA-C and HLA-B allotypes. We conclude that injection of CD4+ T cells into PN skin triggers a series of local immunologically mediated stimulatory events that produce further T cell activation and appearance of both CD4 and CD8+ T cells that express NKRs. (+info)
Local and systemic delivery of a stable aspirin-triggered lipoxin prevents neutrophil recruitment in vivo.
(7/1118)
Aspirin (ASA) triggers a switch in the biosynthesis of lipid mediators, inhibiting prostanoid production and initiating 15-epi-lipoxin generation through the acetylation of cyclooxygenase II. These aspirin-triggered lipoxins (ATL) may mediate some of ASA's beneficial actions and therefore are of interest in the search for novel antiinflammatories that could manifest fewer unwanted side effects. Here, we report that design modifications to native ATL structure prolong its biostability in vivo. In mouse whole blood, ATL analogs protected at carbon 15 [15(R/S)-methyl-lipoxin A4 (ATLa1)] and the omega end [15-epi-16-(para-fluoro)-phenoxy-LXA4 (ATLa2)] were recoverable to approximately 90 and 100% at 3 hr, respectively, compared with a approximately 40% loss of native lipoxin A4. ATLa2 retains bioactivity and, at levels as low as approximately 24 nmol/mouse, potently inhibited tumor necrosis factor-alpha-induced leukocyte recruitment into the dorsal air pouch. Inhibition was evident by either local intra-air pouch delivery (approximately 77% inhibition) or systemic delivery by intravenous injection (approximately 85% inhibition) and proved more potent than local delivery of ASA. Rank order for inhibiting polymorphonuclear leukocyte infiltration was: ATLa2 (10 micrograms, i.v.) approximately ATLa2 (10 micrograms, local) approximately dexamethasone (10 micrograms, local) >ASA (1.0 mg, local). Applied topically to mouse ear skin, ATLa2 also inhibited polymorphonuclear leukocyte infiltration induced by leukotriene B4 (approximately 78% inhibition) or phorbol ester (approximately 49% inhibition), which initiates endogenous chemokine production. These results indicate that this fluorinated analog of natural aspirin-triggered lipoxin A4 is bioavailable by either local or systemic delivery routes and is a more potent and precise inhibitor of neutrophil accumulation than is ASA. (+info)
Histamine response and local cooling in the human skin: involvement of H1- and H2-receptors.
(8/1118)
AIMS: Histamine may contribute locally to cutaneous blood flow control under normal and pathologic conditions. The objective of this study was to observe the influence of skin temperature on histamine vasodilation, and the roles of H1-and H2-receptors using novel noninvasive methods. METHODS: Eleven healthy subjects received, double-blind, single doses of the H1-receptor antagonist cetirizine (10 mg), cetirizine (10 mg) plus the H2-receptor antagonist cimetidine (400 mg), or placebo on separate occasions. Histamine was dosed cumulatively by iontophoresis to the forearm skin at 34 degrees C and 14 degrees C. Laser-Doppler flux (LDF) was measured at the same sites using customised probeholder/iontophoretic chambers with Peltier cooling elements. Finger mean arterial pressure (MAP) was measured and cutaneous vascular conductance calculated as LDF/MAP. RESULTS: Histamine vasodilation was reduced in cold skin. Cetirizine shifted the histamine dose-response at both temperatures: statistically significantly at 14 degrees C only. Combined H1- and H2-receptor antagonism shifted the response significantly at both temperatures. CONCLUSIONS: H1- and H2-receptors mediate histamine-induced skin vasodilation. The sensitivity of these receptors, particularly the H1- receptor, is attenuated at low skin temperature. Whether the reduced effect in cold skin represents specific receptor or postreceptor desensitization, or nonspecific attenuation of cutaneous vasodilation remains to be elucidated. (+info)