High-precision, non-invasive anti-microvascular approach via concurrent ultrasound and laser irradiation.

Antivascular therapy represents a proven strategy to treat angiogenesis. By applying synchronized ultrasound bursts and nanosecond laser irradiation, we developed a novel, selective, non-invasive, localized antivascular method, termed photo-mediated ultrasound therapy (PUT). PUT takes advantage of the high native optical contrast among biological tissues and can treat microvessels without causing collateral damage to the surrounding tissue. In a chicken yolk sac membrane model, under the same ultrasound parameters (1 MHz at 0.45 MPa and 10 Hz with 10% duty cycle), PUT with 4 mJ/cm2 and 6 mJ/cm2 laser fluence induced 51% (p = 0.001) and 37% (p = 0.018) vessel diameter reductions respectively. With 8 mJ/cm2 laser fluence, PUT would yield vessel disruption (90%, p < 0.01). Selectivity of PUT was demonstrated by utilizing laser wavelengths at 578 nm or 650 nm, where PUT selectively shrank veins or occluded arteries. In a rabbit ear model, PUT induced a 68.5% reduction in blood perfusion after 7 days (p < 0.001) without damaging the surrounding cells. In vitro experiments in human blood suggested that cavitation may play a role in PUT. In conclusion, PUT holds significant promise as a novel non-invasive antivascular method with the capability to precisely target blood vessels.

Therapeutic effects of full spectrum light on the development of atopic dermatitis-like lesions in NC/Nga mice.

Full spectrum light (FSL) includes UVA, visible light and infrared light. Many studies have investigated the application of FSL in severe cases of atopic dermatitis (AD) in humans; however, FSL has not yet been studied in an animal model. The purpose of this study was to evaluate the therapeutic effects of FSL on AD-like skin lesions using NC/Nga mice, with the aim of mitigating itching and attenuating the expression of adhesion molecules. We examined the effects of FSL on mite allergen-treated NC/Nga mice by assessing skin symptom severity, ear thickness, serum IgE levels, and the cytokine expression. We examined the histology of lesions using hematoxylin-eosin, toluidine blue and immunohistochemical staining. Our findings suggest that FSL phototherapy exerts positive therapeutic effects on Dermatophagoides farinae (Df)-induced AD-like skin lesions in NC/Nga mice by reducing IgE levels, thus promoting recovery of the skin barrier. The mechanisms by which FSL phototherapy exerts its effects may also involve the inhibition of scratching behavior, reduction of IL-6 levels and reductions in adhesion molecule expression. The present study indicates that FSL phototherapy inhibits the development of AD in NC/Nga mice by suppressing cytokine, chemokine and adhesion molecule expression, and thus, could potentially be useful in treating AD.

Side of the stimulated ear influences the hemispheric balance in coding tonal stimuli.

OBJECTIVE: To evaluate whether the side of stimulated ear affects the hemispheric asymmetry of auditory evoked cortical activations. METHODS: Using a whole-head neuromagnetometer, we recorded neuromagnetic approximately 100 ms responses (N100m) in 21 healthy right-handers to 100 ms 1 kHz tones delivered alternatively to left and right ear. RESULTS: Although the peak latencies of N100m were shorter in contralateral than in ipsilateral hemisphere, the difference was significant only for the left ear stimulation. Based on the relative N100m amplitudes across hemispheres, the laterality evaluation showed a rightward predominance of N100m activation to tone stimuli, but the lateralization toward the right hemisphere was more apparent by the left than by the right ear stimulation (laterality index: -0.27 versus -0.10, p=0.008). Within the right hemisphere, the N100m was 2-4 mm more posterior for left ear than for right ear stimulation. CONCLUSIONS: The hemispheric asymmetry in auditory processing depends on the side of the stimulated ear. The more anterior localization of right N100m responses to ipsilateral than to contralateral ear stimulation suggests that there might be differential neuronal populations in the right hemisphere for processing spatially different auditory inputs.

Dietary grape-seed proanthocyanidin inhibition of ultraviolet B-induced immune suppression is associated with induction of IL-12.

We have shown previously that dietary grape seed proanthocyanidins (GSPs) inhibit UVB-induced photocarcinogenesis in mice. As UVB-induced immune suppression has been implicated in the development of skin cancer risk, we investigated whether dietary GSPs can modulate the effects of UVB on the immune system. We found that the UVB-induced (180 mJ/cm2) ear swelling response (inflammatory reaction) was significantly lower in mice fed with a GSP-supplemented (0.5 and 1.0%, w/w) diet than mice fed with the standard AIN76A diet. Dietary GSPs markedly inhibited UVB-induced (180 mJ/cm2) suppression of contact hypersensitivity responses in a local model of immunosuppression but had only moderate inhibitory effect in a systemic model of immunosuppression. Dietary GSPs reduced the UVB-induced increase in immunosuppressive cytokine interleukin (IL)-10 in skin and draining lymph nodes compared with mice that did not receive GSPs. In contrast, GSPs enhanced the production of immunostimulatory cytokine IL-12 in the draining lymph nodes. Intraperitoneal injection of GSPs-fed mice with a neutralizing anti-IL-12 antibody abrogated the protective effects of the GSPs against UVB-induced suppression of the contact hypersensitivity response. These data indicate for the first time that GSPs modulate UVB-induced immunosuppression and suggest that this may be one of the possible mechanisms by which they prevent photocarcinogenesis in mice.

Comparative potency of broad-band and narrow-band phototherapy sources to induce edema, sunburn cells and urocanic acid photoisomerization in hairless mouse skin.

The Philips TL01 narrow-band (311-313 nm) fluorescent lamp provides effective phototherapy for psoriasis and atopic eczema while emitting less erythemogenic radiation than conventional broad-band (e.g. Philips TL12; 270-350 nm) sources. We studied the potency of TL01 and TL12 radiation to induce edema and sunburn cells (SBC) and to photoisomerize naturally occurring trans-urocanic acid (UCA) to cis-UCA in hairless mouse skin. Cis-UCA has immunosuppressive properties and is a putative mediator of UV-induced suppression of immune responses. For each source, there was UV dose dependence for all three responses. Within the dose ranges used, the potency ratio of TL12:TL01 radiation to induce equivalent edema and SBC was about 6:1. However, the potency ratio to induce cis-UCA was less than 2.3:1. Therefore, at a given level of edema or SBC induction, TL01 was more efficient than TL12 at UCA photoisomerization. The TL01 induction of immunomodulating cis-UCA, while causing minimal skin injury, may relate to the therapeutic efficacy of this source in skin conditions with an immunological component.

Ultraviolet radiation suppresses mouse-ear edema induced by topical application of arachidonic acid.

The effect of ultraviolet (UV) radiation on arachidonic acid (AA) cascade was examined using an in vivo model. Mouse ear lobes were painted with 1 mg AA, and the maximum response of ear swelling was measured 1 h after challenge. Arachidonic-acid-induced ear swelling was significantly suppressed by preexposure to topical psoralen plus noninflammatory doses of long-wave UV radiation (PUVA) or middle-wave UV (UVB) radiation. Ultraviolet radiation may interfere with AA pathways to suppress ear swelling since AA-induced ear swelling is considered to be mediated by metabolites derived from exogenous AA. The results may relate to the therapeutic mechanisms of UV radiation in psoriasis in which the eicosanoid cascade is involved.

A long-term effect of X rays on thermal sensitivity of the mouse ear.

The response of the mouse ear to hyperthermia was investigated after single doses of X rays. A dose of 15 Gy, which alone caused no visible effect, increased thermal sensitivity at 1-2 weeks after irradiation. There was a slight recovery at 4-6 weeks but thermal sensitivity was still increased at 6 months. When heat treatment was given at 1 week or 24 weeks after X-ray doses ranging from 9-18 Gy, it was found that thermal sensitivity increased as the dose was increased above 10 Gy. Although there are reports which indicate that prior radiotherapy given more than two months earlier does not affect normal tissue response to the mild hyperthermia currently being used to treat patients, more aggressive heat therapy may produce unexpected responses at previously irradiated sites.