Skin blood flow response to topically applied methyl nicotinate: Possible mechanisms.

BACKGROUND: Methyl nicotinate (MN) induces a local cutaneous erythema in the skin and may be valuable as a local provocation in the assessment of microcirculation and skin viability. The mechanisms through which MN mediates its vascular effect are not fully known. The aim of this study was to characterize the vasodilatory effects of topically applied MN and to study the involvement of nitric oxide (NO), local sensory nerves, and prostaglandin-mediated pathways. METHODS: MN was applied on the skin of healthy subjects in which NO-mediated (L-NMMA), nerve-mediated (lidocaine/prilocaine), and cyclooxygenase-mediated (NSAID) pathways were selectively inhibited. Microvascular responses in the skin were measured using laser speckle contrast imaging (LSCI). RESULTS: NSAID reduced the MN-induced perfusion increase with 82% (P < .01), whereas lidocaine/prilocaine reduced it with 32% (P < .01). L-NMMA did not affect the microvascular response to MN. CONCLUSION: The prostaglandin pathway and local sensory nerves are involved in the vasodilatory actions of MN in the skin.

Comparison of two different laser photobiomodulation protocols on the viability of random skin flap in rats.

To identify the best low level laser photobiomodulation application site at the same irradiation time to increase the viability of the skin flap in rats. Eighteen male rats (Rattus norvegicus: var. Albinus, Rodentia Mammalia) were randomly distributed into three groups (n = 6). Group I (GI) was submitted to simulated laser photobiomodulation; group II (GII) was submitted to laser photobiomodulation at three points in the flap cranial base, and group III (GIII) was submitted to laser photobiomodulation at 12 points distributed along the flap. All groups were irradiated with an Indium, Galium, Aluminum, and Phosphorus diode laser (InGaAlP), 660 nm, with 50 mW power, irradiated for a total time of 240 s in continuous emission mode. The treatment started immediately after performing the cranial base random skin flap (10 × 4 cm2 dimension) and reapplied every 24 h, with a total of five applications. The animals were euthanized after the evaluation of the percentage of necrosis area, and the material was collected for histological analysis on the seventh postoperative day. GII animals presented a statistically significant decrease for the necrosis area when compared to the other groups, and a statistically significant increase in the quantification of collagen when compared to the control. We did not observe a statistical difference between the TGFß and FGF expression in the different groups evaluated. The application of laser photobiomodulation at three points of the flap cranial base was more effective than at 12 points regarding the reduction of necrosis area.

Photobiomodulation of a flowable matrix in a human skin ex vivo model demonstrates energy-based enhancement of engraftment integration and remodeling.

The use of dermal substitutes to treat skin defects such as ulcers has shown promising results, suggesting a potential role for skin substitutes for treating acute and chronic wounds. One of the main drawbacks with the use of dermal substitutes is the length of time from engraftment to graft take, plus the risk of contamination and failure due to this prolonged integration. Therefore, the use of adjuvant energy-based therapeutic modalities to augment and accelerate the rate of biointegration by dermal substitute engraftments is a desirable outcome. The photobiomodulation (PBM) therapy modulates the repair process, by stimulating cellular proliferation and angiogenesis. Here, we evaluated the effect of PBM on a collagen-glycosaminoglycan flowable wound matrix (FWM) in an ex vivo human skin wound model. PBM resulted in accelerated rate of re-epithelialization and organization of matrix as seen by structural arrangement of collagen fibers, and a subsequent increased expression of alpha-smooth muscle actin (α-SMA) and vascular endothelial growth factor A (VEGF-A) leading to an overall improved healing process. The use of PBM promoted a beneficial effect on the rate of integration and healing of FWM. We therefore propose that the adjuvant use of PBM may have utility in enhancing engraftment and tissue repair and be of value in clinical practice.

Hyperbaric oxygen therapy as a prevention modality for radiation damage in the mandibles of mice.

BACKGROUND: Radiation therapy (RT) as part head and neck cancer treatment often leads to irradiation of surrounding normal tissue, such as mandibular bone. A reduced reparative capacity of the bone can lead to osteoradionecrosis (ORN). Hyperbaric oxygen therapy (HBOT) is used to treat ORN, based on its potential to raise the oxygen tension in tissues. However, prevention of radiation-induced damage is of great interest. Our purpose was to investigate whether HBOT could prevent radiation-induced damage to murine mandibles. METHODS: Twenty-eight mice were irradiated in the head and neck region with a single dose (15 Gy) and half of them were subsequently subjected to HBOT. Another 14 mice did not receive any treatment and served as controls. Ten and 24 weeks after RT, mandibles were harvested and analysed histologically and by microcomputed tomography (micro-CT). RESULTS: Micro-CT analysis showed a reduction in relative bone volume by RT, which was partly recovered by HBOT. Trabecular thickness and separation were also positively influenced by HBOT. Morphologically, HBOT suppressed the osteoclast number, indicating decreased resorption, and decreased the amount of lacunae devoid of osteocytes, indicating increased bone viability. CONCLUSIONS: HBOT was able to partly reduce radiation-induced effects on microarchitectural parameters, resorption, and bone viability in mouse mandibles. HBOT could therefore potentially play a role in the prevention of radiation-induced damage to human mandibular bone.

Sustratos electrohilados de poli(hidroxibutirato-co-hidroxihexanoato) con glicósidos para reparación de la lesión medular / Glycosides-bearing electrospun poly(hydroxybutyrate-co-hydroxyhexanoate) substrates for the repair of injured spinal cord

Objetivo: Obtención mediante electrohilado de fibras micro- y submicrométricas de poliésteres funcionalizadas con glicósidos que constituyen elementos estructurales de proteoglicanos, para su uso en la reparación del tejido medular. Material y métodos: Las fibras se prepararon a partir de disoluciones de poli(3-hidroxibutirato-co-3-hidroxihexanoato) con glicósidos sintéticos mediante electrohilado variando sistemáticamente las condiciones del proceso. La morfología de las fibras fue analizada mediante microscopía electrónica de barrido. Asimismo, se evaluó la estabilidad de la interacción entre el glicósido y la fibra en medio acuoso, y su toxicidad en cultivos de células neurales. Resultados: La morfología de las fibras obtenidas depende principalmente de los parámetros de la disolución. En medio acuoso, el glicósido sulfatado se liberó de las fibras más lentamente que el que no tenía dicho grupo funcional. La viabilidad de las células neurales no se vio afectada por los glicósidos. Conclusión: La preparación de microfibras alineadas de poliéster funcionalizadas con glicósidos es posible. La mayor parte del glicósido permanece retenido en las fibras sumergidas en agua después de varios días. El electrohilado es una técnica muy accesible y versátil para la fabricación de soportes en estrategias de terapia celular de lesiones medulares (AU)

Objective: Preparation of functionalized micro- and submicrofibers by electrospinning of polyesters with glycosides which are structural elements of proteoglycans, for application to the repair of spinal cord lesions. Material and methods: Solutions of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) with synthetic glycosides were prepared varying systematically the processing conditions. Fiber morphology assessed by scanning electron microscopy. The stability of the interaction between the glycoside and the polymer fiber was evaluated in aqueous medium, and their toxicity in cultures of neural cells. Results: The fiber morphology was altered mainly by the solution parameters. In aqueous medium, the glycoside with a sulfate group was released from fibers at slower rate than the non-sulfated glycoside. The viability of neural cells was not affected by the glycosides. Conclusion: It is possible to fabricate aligned polyester micro fibers with glycosides. Most of the glycoside present in the fibers remains in the substrate after extraction in water for several days. Electrospinning is a very accessible and versatile technique for application to strategies of cellular therapy in spinal cord injuries (AU)

The effects of low-dose irradiation on inflammatory response proteins in a 3D reconstituted human skin tissue model.

Skin responses to moderate and high doses of ionizing radiation include the induction of DNA repair, apoptosis and stress response pathways. Additionally, numerous studies indicate that radiation exposure leads to inflammatory responses in skin cells and tissue. However, the inflammatory response of skin tissue to low-dose radiation (≤10 cGy) is poorly understood. To address this, we have utilized a reconstituted human skin tissue model (MatTek EpiDermFT™) and assessed changes in 23 cytokines, 24 and 48 h after treatment of skin with either 3 or 10 cGy low dose of radiation. Three cytokines, IFN-γ, IL-2, MIP-1α, were significantly altered in response to low-dose radiation. In contrast, seven cytokines were significantly altered in response to a high radiation dose of 200 cGy (IL-2, IL-10, IL-13, IFN-γ, MIP-1α, TNFα and VEGF) or the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (G-CSF, GM-CSF, IL-1α, IL-8, MIP-1α, MIP-1ß and RANTES). Additionally, radiation induced inflammation appears to have a distinct cytokine response relative to the nonradiation induced stressor, TPA. Overall, these results indicate that there are subtle changes in the inflammatory protein levels after exposure to low-dose radiation and this response is a subset of what is seen after a high dose in a human skin tissue model.

The effects of different doses of 670 nm diode laser on skin flap survival in rats.

PURPOSE: To investigate the effects of different low-level laser therapy (LLLT) doses on random skin flap rats. METHODS: Forty Wistar rats were randomly divided in four groups. The control group (CG) was not irradiated. The experimental groups were irradiated with a diode laser 670 nm with different energies per point: group 2 (G2) with 0.06 J; group 3 (G3) 0.15 J and group 4 (G4) 0.57 J. The three groups were irradiated in 12 equally distributed points in the cranial skin flap portion. They were submitted to the irradiation during the immediate, first and second postoperative days. The necrosis area was evaluated in the seventh postoperative day. RESULTS: The CG shows 49.35% of necrosis area in the skin flap; G2, 39.14%; G3, 47.01% and G4, 29.17% respectively. There was a significantly difference when G4 was compared with CG`s skin flap necrosis area. CONCLUSION: The low-level laser therapy diode 670 nm with 0.57 J energy per point increases the survival in randomic skin flap rats.

The effects of different doses of 670 nm diode laser on skin flap survival in rats / O efeito de diferentes doses de laser de diodo 670 nm na viabilidade de retalho cutâneo randômico em ratos

PURPOSE: To investigate the effects of different low-level laser therapy (LLLT) doses on random skin flap rats. METHODS: Forty Wistar rats were randomly divided in four groups. The control group (CG) was not irradiated. The experimental groups were irradiated with a diode laser 670 nm with different energies per point: group 2 (G2) with 0.06 J; group 3 (G3) 0.15 J and group 4 (G4) 0.57 J. The three groups were irradiated in 12 equally distributed points in the cranial skin flap portion. They were submitted to the irradiation during the immediate, first and second postoperative days. The necrosis area was evaluated in the seventh postoperative day. RESULTS: The CG shows 49.35 percent of necrosis area in the skin flap; G2, 39.14 percent; G3, 47.01 percent and G4, 29.17 percent respectively. There was a significantly difference when G4 was compared with CG`s skin flap necrosis area. CONCLUSION: The low-level laser therapy diode 670 nm with 0.57 J energy per point increases the survival in randomic skin flap rats.

OBJETIVO: Investigar os efeitos de diferentes doses de laserterapia de baixa intensidade na viabilidade de retalhos cutâneos randômicos em ratos. MÉTODOS: Quarenta ratos Wistar foram randomizadamente distribuídos em quatro grupos. O grupo controle (GC) não foi irradiado. Os animais dos grupos experimentais foram irradiados por laser de diodo (670 nm) com as seguintes energias ofertadas por ponto: grupo 2 (G2) 0,06J; grupo 3 (G3) 0,15 J e grupo 4 (G4) 0,57 J. Os três grupos foram irradiados em 12 pontos igualmente distribuídos na porção cranial do retalho cutâneo. Todos os animais dos grupos 2, 3 e 4 foram submetidos ao protocolo de irradiação por três dias consecutivos, iniciando no pós-operatório imediato. A área necrótica foi avaliada no sétimo dia pós-operatório. RESULTADOS: A porcentagem de área necrótica apresentou-se da seguinte forma, nos diferentes grupos: GC= 49,35 por cento, G2= 39,14 por cento, G3= 47,01 e G4= 29,17 por cento. Foi encontrada diferença estatisticamente significante quando se compararam os dados entre GC e G4. CONCLUSÃO: A irradiação com laser de diodo (670 nm) de baixa intensidade, com oferta de 0,57 J de energia por ponto influenciou positivamente a viabilidade de retalhos cutâneos randômicos em ratos.

Low-level laser therapy on the viability of skin flap in rats subjected to deleterious effect of nicotine.

OBJECTIVE: The purpose of this study was to evaluate the effect of 830-nm laser in blocking the action of nicotine on the viability of skin flap. BACKGROUND DATA: The authors have analyzed the deleterious effect of cigarette smoke or nicotine on the skin flap alone with evidence of increased skin necrosis in the flap. MATERIALS AND METHODS: Twenty-four Wistar-albino rats were divided into three groups of eight animals each: Group 1 (control), subjected to a surgical technique to obtain a flap for cranial base, laser irradiation simulation, and a subcutaneous injection of saline; Group 2, similar to Group 1, with subcutaneous injection of nicotine (2 mg/kg/day) for a period of 1 week before and 1 week after surgery; and Group 3, similar to Group 2, with skin flaps subjected to a λ 830-nm laser irradiation. The laser parameters used were: power 30 mW, beam area 0.07 cm(2), irradiance 429 mW/cm(2), irradiation time 84 sec, total energy 2.52 J, and energy density 36 J/cm(2). The laser was used immediately after surgery and for 4 consecutive days, in one point at 2.5 cm of the flap cranial base. The areas of necrosis were examined by two macroscopic analyses: paper template and Mini-Mop(®). The pervious blood vessels were also counted. RESULTS: The results were statistically analyzed by ANOVA and post-test contrast orthogonal method (multiple comparisons), showing that the laser decreased the area of necrosis in flaps subjected to nicotine, and consequently, increased the number of blood vessels (p < 0.05). CONCLUSIONS: The laser proved to be an effective way to decrease the area of necrosis in rats subjected to nicotine, making them similar to the control group.

Preoperative shock wave treatment enhances ischemic tissue survival, blood flow and angiogenesis in a rat skin flap model.

INTRODUCTION: Extracorporeal shock wave treatment (ESWT) has recently been shown to enhance skin flap survival. However, the bio-mechanisms operating during preoperative ESWT remain unclear. The aim of our study was to investigate whether preoperative ESWT can improve blood flow in ischemic skin flaps and to elucidate its possible mechanisms. METHODS: 14 male-rats were randomized into two groups and an oversized ventral random-pattern flap was raised. Experimental group received extracorporeal shock-wave treatment (ESWT) with an energy of 500 mJ/mm(2) seven days prior to total flap elevation, while control group received no treatment prior to total flap elevation. Seven days postoperatively, surviving flap area, perfused flap area, microvessel density and VEGF concentration were measured. RESULTS: Surviving flap area (59.43 ± 14.72 % to 42.71 ± 10.75 %, p = 0.026), perfused flap area (62.00 ± 8.58 % to 45.14 ± 10.50 %, p = 0.007), microvessel density (18.13 ± 5.11 to 11.09 ± 1.12, p = 0.016) and VEGF to total protein ratio (0.2107 ± 0.0935 to 0.0123 ± 0.0069, p = 0.008) were significantly elevated in the ESWT group. CONCLUSION: Preoperative ESWT can improve skin flap survival through enhanced topical blood perfusion and neovascularization via elevation of angio-active factors.

Absence of nonlinear responses in cells and tissues exposed to RF energy at mobile phone frequencies using a doubly resonant cavity.

A doubly resonant cavity was used to search for nonlinear radiofrequency (RF) energy conversion in a range of biological preparations, thereby testing the hypothesis that living tissue can demodulate RF carriers and generate baseband signals. The samples comprised high-density cell suspensions (human lymphocytes and mouse bone marrow cells); adherent cells (IMR-32 human neuroblastoma, G361 human melanoma, HF-19 human fibroblasts, N2a murine neuroblastoma (differentiated and non-differentiated) and Chinese hamster ovary (CHO) cells) and thin sections or slices of mouse tissues (brain, kidney, muscle, liver, spleen, testis, heart and diaphragm). Viable and non-viable (heat killed or metabolically impaired) samples were tested. Over 500 cell and tissue samples were placed within the cavity, exposed to continuous wave (CW) fields at the resonant frequency (f) of the loaded cavity (near 883 MHz) using input powers of 0.1 or 1 mW, and monitored for second harmonic generation by inspection of the output at 2f. Unwanted signals were minimised using low pass filters (≤ 1 GHz) at the input to, and high pass filters (≥ 1 GHz) at the output from, the cavity. A tuned low noise amplifier allowed detection of second harmonic signals above a noise floor as low as -169 dBm. No consistent second harmonic of the incident CW signals was detected. Therefore, these results do not support the hypothesis that living cells can demodulate RF energy, since second harmonic generation is the necessary and sufficient condition for demodulation.

Factors influencing survival of free-flap in reconstruction for cancer of the head and neck: a literature review.

Microvascular free tissue transfer is a reliable technique for head and neck reconstruction with success rates of 90-99%. Currently, there is no consensus concerning antithrombotic agents, antibiotics, or monitoring techniques. Therefore, the aim of this study was to review current literature dealing with microvascular free-tissue transfer and factors influencing the outcome. In addition to excellent microsurgical techniques, coupling devices are a promising new technique, but are not useful in all arteries. Antibiotics should be given in three doses, as a more lengthy dosage time seems to have no advantage. The risk for elderly patients can be best assessed by the American Society of Anesthesiologists (ASA) score, but early mobilization, including intense chest physiotherapy, is important. Anticoagulation can be considered in cases of small vessels, significant size mismatch, vein graft, or vessels of poor quality. Monitoring should be done hourly during the first 24 hours and then every 4 hours for the next 2 postoperative days.

The effects of 660 nm and 780 nm laser irradiation on viability of random skin flap in rats.

BACKGROUND AND OBJECTIVE: Some studies have shown that laser phototherapy is able to increase skin flap viability by decreasing the necrotic area and increasing neoangiogenesis. However, the mechanism by which laser acts on cells is not fully understood. The present study investigated the effects of two different laser wavelengths at 30 and 40 J/cm(2) on the viability of skin flap in rats. MATERIAL AND METHODS: Sixty male animals were used in this study. They were distributed into the following groups (n = 12 each group): control group, group irradiated with 660 nm at 30 J/cm(2); group irradiated with 780 nm, at 30 J/cm(2), group irradiated with 660 nm at 40 J/cm(2); and group irradiated with 780 nm at 40 J/cm(2). The skin flap was performed on the back of all animals studied, with a plastic sheet interposed between the flap and the donor site. Laser irradiation was done immediately after the surgery and on days 1, 2, 3, and 4 post-surgery. The percentage of the necrotic area of the flap was calculated at day 7 post-surgery. RESULTS: Control group showed a necrotic area of 62.83%. Interestingly, no statistically significant differences were found among the treated groups and the control group. CONCLUSION: This present study showed that 660 nm and 780 nm lasers at doses of 30 and 40 J/cm(2) were not effective for decreasing the necrotic area of the skin flaps in rats.

Lack of chick embryotoxicity after 20 kHz, 1.1 mT magnetic field exposure.

This investigation was undertaken because biological studies to evaluate the effects of intermediate frequency magnetic fields are insufficient. White Leghorn fertile eggs (60/group) were either exposed to a 20 kHz, 1.1 mT(rms) sinusoidal magnetic field or sham-exposed during the first 2, 7, or 11 days of embryogenesis. Lower dose exposures at 0.011 and 0.11 mT(rms) for 2 days were also conducted to elucidate possible dose-response relationships. Additional eggs given all-trans-retinoic acid, a teratogen, were exposed to the 1.1 mT(rms) magnetic field for the same periods to investigate the modification of embryotoxicity. After exposure, embryos were examined for mortality and developmental abnormalities. Developmental stage, number of somite pairs, and other developmental endpoints were also evaluated. Experiments were triplicated and conducted in a blind fashion. No exposure-related changes were found in any of the endpoints in intact embryos exposed to 1.1 mT(rms) or to the lower doses of 0.11 and 0.011 mT(rms) magnetic fields. Retinoic acid administration produced embryotoxic responses, which were embryonic death and developmental abnormalities, in 40-60% of embryos in the sham-exposed groups. The magnitude of these responses was not changed significantly by the magnetic field exposures. Under the present experimental conditions, exposure to 20 kHz magnetic field up to 1.1 mT(rms) was not embryotoxic in the chick and did not potentiate the embryotoxic action of retinoic acid.

Low-level laser therapy (670 nm) on viability of random skin flap in rats.

This study investigated the effects of 670 nm laser, at different fluences, on the viability of skin flap in rats. One hundred male animals were used. The animals were divided into control group; group treated with 3 J/cm(2); group treated with 6 J/cm(2); group treated with 12 J/cm(2) and group treated with 24 J/cm(2). The skin flap was made on the backs of all animals studied, with a plastic sheet interposed between the flap and the donor site. Laser irradiation was done immediately after the surgery and on days 1, 2, 3 and 4 after surgery. The percentage of necrosis of the flap was calculated at the 7th postoperative day. Additionally, a sample of each flap was collected to enable us to count the blood vessels. Treated animals showed a statistically significant smaller area of necrosis than did the control group. The necrosis in the treated groups was 41.82% (group 2), 36.51% (group 3), 29.45% (group 4) and 20.37% (group 5). We also demonstrated that laser irradiation at 670 nm, at all doses used, had a stimulatory effect on angiogenesis. Our study showed that the 670 nm laser was efficient to increase the viability of the skin flap, at all fluences used, with a tendency of reaching better results at higher doses.

Tumor recovery by angiogenic switch from sprouting to intussusceptive angiogenesis after treatment with PTK787/ZK222584 or ionizing radiation.

Inhibitors of angiogenesis and radiation induce compensatory changes in the tumor vasculature both during and after treatment cessation. To assess the responses to irradiation and vascular endothelial growth factor-receptor tyrosine kinase inhibition (by the vascular endothelial growth factor tyrosine kinase inhibitor PTK787/ZK222854), mammary carcinoma allografts were investigated by vascular casting; electron, light, and confocal microscopy; and immunoblotting. Irradiation and anti-angiogenic therapy had similar effects on the tumor vasculature. Both treatments reduced tumor vascularization, particularly in the tumor medulla. After cessation of therapy, the tumor vasculature expanded predominantly by intussusception with a plexus composed of enlarged sinusoidal-like vessels containing multiple transluminal tissue pillars. Tumor revascularization originated from preserved alpha-smooth muscle actin-positive vessels in the tumor cortex. Quantification revealed that recovery was characterized by an angiogenic switch from sprouting to intussusception. Up-regulated alpha-smooth muscle actin-expression during recovery reflected the recruitment of alpha-smooth muscle actin-positive cells for intussusception as part of the angio-adaptive mechanism. Tumor recovery was associated with a dramatic decrease (by 30% to 40%) in the intratumoral microvascular density, probably as a result of intussusceptive pruning and, surprisingly, with only a minimal reduction of the total microvascular (exchange) area. Therefore, the vascular supply to the tumor was not severely compromised, as demonstrated by hypoxia-inducible factor-1alpha expression. Both irradiation and anti-angiogenic therapy cause a switch from sprouting to intussusceptive angiogenesis, representing an escape mechanism and accounting for the development of resistance, as well as rapid recovery, after cessation of therapy.

Thrombospondin-1 and CD47 limit cell and tissue survival of radiation injury.

Radiation, a primary mode of cancer therapy, acutely damages cellular macromolecules and DNA and elicits stress responses that lead to cell death. The known cytoprotective activity of nitric oxide (NO) is blocked by thrombospondin-1, a potent antagonist of NO/cGMP signaling in ischemic soft tissues, suggesting that thrombospondin-1 signaling via its receptor CD47 could correspondingly increase radiosensitivity. We show here that soft tissues in thrombospondin-1-null mice are remarkably resistant to radiation injury. Twelve hours after 25-Gy hindlimb irradiation, thrombospondin-1-null mice showed significantly less cell death in both muscle and bone marrow. Two months after irradiation, skin and muscle units in null mice showed minimal histological evidence of radiation injury and near full retention of mitochondrial function. Additionally, both tissue perfusion and acute vascular responses to NO were preserved in irradiated thrombospondin-1-null hindlimbs. The role of thrombospondin-1 in radiosensitization is specific because thrombospondin-2-null mice were not protected. However, mice lacking CD47 showed radioresistance similar to thrombospondin-1-null mice. Both thrombospondin-1- and CD47-dependent radiosensitization is cell autonomous because vascular cells isolated from the respective null mice showed dramatically increased survival and improved proliferative capacity after irradiation in vitro. Therefore, thrombospondin-1/CD47 antagonists may have selective radioprotective activity for normal tissues.

The impact of hydration changes in fresh bio-tissue on THz spectroscopic measurements.

We present a study of how residual hydration in fresh rat tissue samples can vastly alter their extracted terahertz (THz) optical properties and influence their health assessment. Fresh (as opposed to preserved) tissue most closely mimics in vivo conditions, but high water content creates many challenges for tissue handling and THz measurement. Our THz measurements of fresh tissue over time highlight the effect of tissue hydration on tissue texture and dimension, the latter directly influencing the accuracy of calculated optical properties. We then introduce lyophilization (freeze drying) as a viable solution for overcoming hydration and freshness problems. Lyophilization removes large amounts of water while retaining sample freshness. In addition, lyophilized tissue samples are easy to handle and their textures and dimensions do not vary over time, allowing for consistent and stable THz measurements. A comparison of lyophilized and fresh tissue shows for the first time that freeze drying may be one way of overcoming tissue hydration issues while preserving tissue cellular structure. Finally, we compare THz measurements from fresh tissue against necrotic tissue to verify freshness over time. Indeed, THz measurements from fresh and necrotic tissues show marked differences.

A radiation damage repair model for normal tissues.

A cellular Monte Carlo model describing radiation damage and repair in normal epithelial tissues is presented. The deliberately simplified model includes cell cycling, cell motility and radiation damage response (cell cycle arrest and cell death) only. Results demonstrate that the model produces a stable equilibrium system for mean cell cycle times in the range 24-96 h. Simulated irradiation of these stable equilibrium systems produced a range of responses that are shown to be consistent with experimental and clinical observation, including (i) re-epithelialization of radiation-induced lesions by a mixture of cell migration into the wound and repopulation at the periphery; (ii) observed radiosensitivity that is quantitatively consistent with both rate of induction of irreparable DNA lesions and, independently, with the observed acute oral and pharyngeal mucosal reactions to radiotherapy; (iii) an observed time between irradiation and maximum toxicity that is consistent with experimental data for skin; (iv) quantitatively accurate predictions of low-dose hyper-radiosensitivity; (v) Gomperzian repopulation for very small lesions ( approximately 2000 cells) and (vi) a linear rate of re-epithelialization of 5-10 microm h(-1) for large lesions (>15 000 cells).