A feasible way to explore real blood vessels thermal responses to laser irradiation by combing optical clearing and the reflectance spectra measurements: animal experiment study.

Laser therapy has been widely used to treat port-wine stains (PWS) and other cutaneous vascular lesions via selective photothermolysis. Animal models are a valuable tool for investigating thermal responses beneath the skin. However, in previous animal experiments, such as the dorsal skin chamber model, one side of the skin was removed, resulting in the loss of mechanical support for the target blood vessel. In this study, the optical clearing technique was applied to the dorsal skin, allowing direct observation of real thermal responses within the tissue without removing the covering skin. The target blood vessels were irradiated with a pulsed 1064 nm Nd: YAG laser. The corresponding thermal responses were recorded using a CCD camera. Additionally, variations in skin reflectance spectra were measured before and after laser irradiation. Due to the optical clearing and reflectance spectra measurement, vessel responses such as contraction, reperfusion, and full occlusion were correlated with specific variation patterns in reflectance spectral signals.

Multidisciplinary Management of Angiosarcoma - A Review.

Angiosarcomas (AS) are a diverse group of soft tissue sarcomas, arising from blood and lymphatic vessels. They frequently present in the elderly, and in patients with previous radiation or lymphedema. A wide range of genetic derangements contribute to their development, and AS histology is often high-grade in keeping with aggressive disease biology. The clinical presentation, while often innocuous, is marked by its infiltrative and aggressive nature, with a proclivity for metastatic spread, and outcomes are often poor. Surgery is performed for localized, resectable cases. A multidisciplinary approach, appropriately employing surgery, radiation, chemotherapy, or potentially recently approved immune-oncology agents, can result in positive outcomes.

Laser treatment of synovial inflammatory process in experimentally induced microcrystalline arthritis in Wistar rats.

The presence of intra-articular crystals is detected in different articular pathologies of acute or chronic nature. The aim of this work was to analyze the action of the indium gallium aluminum and phosphorus (InGaAlP) (λ = 670 nm) laser on the synovial membrane present in the knee joint in experimentally induced microcrystalline arthritis in male adult Wistar rats. The animals were divided into three experimental groups (n = 24): control (A), experimentally induced arthritis (B), experimentally induced arthritis+InGaAlP laser therapy (C). The laser treatment was made daily in the patellar region of the right knee after 48 h of the experimental induction. After 7, 14, and 21 days of therapy, the rats were euthanized and the right knees were removed and processed for histomorphometric, immunohistochemical, ultrastructural, and biochemical investigation of the synovium. The number of granulocytes on the 14th and 21st days was higher in B and lower in C and, lastly, in A. The number of fibroblasts on the 14th and 21st days was similar between A and C and below B. The number of blood vessels on the 21st day was higher in B than in the other groups. The positive number of cells for the TUNEL test was higher on the 14th and 21st days in B compared to the others. The percentage of tissue area occupied by birefringent collagen fibers was higher in B on the 21st day than in the others. The ultrastructure of cells showed fibroblast-like morphology in all groups and periods evaluated. The quantification of glycosaminoglycans did not present significant differences between the groups in all the experimental periods. The amount of hydroxyproline was higher in B compared to the other groups on the 14th and 21st days. The content of non-collagen proteins was higher in B on the 21st day in relation to the other groups. Quantification of TNF-α on the 21st day was higher in A and B than in C. For TGF-ß on the 21st day, groups B and C presented similar and higher values than A. For MMP-13, groups A and B presented data similar to and above C. In relation to ADAMT-S4, on the 21st day, groups B and C presented data similar to and lower than A. InGaAlP-670 nm therapy reduced the inflammatory process and tissue injuries of the synovial membrane in comparison to the untreated group, indicating its potential utilization in clinical studies aiming in the recovery of acute arthritis in patients.

Radiation-induced myocardial fibrosis: Mechanisms underlying its pathogenesis and therapeutic strategies.

Radiation-induced myocardial fibrosis (RIMF) is a potentially lethal clinical complication of chest radiotherapy (RT) and a final stage of radiation-induced heart disease (RIHD). RIMF is characterized by decreased ventricular elasticity and distensibility, which can result in decreased ejection fraction, heart failure and even sudden cardiac death. Together, these conditions impair the long-term health of post-RT survivors and limit the dose and intensity of RT required to effectively kill tumour cells. Although the exact mechanisms involving in RIMF are unclear, increasing evidence indicates that the occurrence of RIMF is related to various cells, regulatory molecules and cytokines. However, accurately diagnosing and identifying patients who may progress to RIMF has been challenging. Despite the urgent need for an effective treatment, there is currently no medical therapy for RIMF approved for routine clinical application. In this review, we investigated the underlying pathophysiology involved in the initiation and progression of RIMF before outlining potential preventative and therapeutic strategies to counter this toxicity.

Thermal coagulum formation and hemostasis during repeated multipulse Nd:YAG laser treatment of cutaneous vascular lesions: animal experiment study.

Laser therapy has been widely used to treat port-wine stain (PWS) and other cutaneous vascular lesions via selective photothermolysis. High incident laser fluence is always prohibited in clinic to prevent the thermal damage in normal skin tissue, leading to insufficient energy deposition on the target blood vessel and incomplete clearance of PWS lesion. In this study, repeated multipulse laser (RMPL) irradiation was proposed to induce acute thermal damage to target blood vessels with low incident fluence (40 J/cm2 for 1064-nm Nd:YAG laser). The feasibility of the method was investigated using animal models. Repeated multipulse irradiation cycles with 10-min intervals were performed in RMPL. A hamster dorsal skin chamber model with a visualization system was constructed to investigate the instant generation of thermal coagulum and relevant hemostasis by thrombus formation during and after irradiation under 1064 nm Nd:YAG single multipulse laser (SMPL) and RMPL irradiation. The diameter of the target blood vessel and the size of thermal coagula were measured before and after laser irradiation. The reflectance spectra of the dorsal skin were measured by a reflectance spectrometer during RMPL. Stasis thermal coagula that clogged the vessel lumen were generated during SMPL irradiation with low incident fluence. However, there was no acute thermal damage of blood vessels. Reflectance spectra measurement showed that the generation of thermal coagula and subsequent thrombus formation increases blood absorption by more than 10% within the first 10 min after laser irradiation. Acute vessel thermal damage could be induced in the target blood vessel by RMPL with low incident fluence of 40 J/cm2. Compared with our previous SMPL study, nearly 30% reduction in incident laser fluence was achieved by RMPL. Low fluence RMPL may be a promising approach to improve the therapeutic outcome for patients with cutaneous vascular lesions by improving energy deposition on the target blood vessel.

Experimental investigations on thermal effects of a long-pulse alexandrite laser on blood vessels and its comparison with pulsed dye and Nd:YAG lasers.

Laser has been widely used in the treatment of vascular skin diseases, such as port wine stain, due to the effect of selective photothermolysis in laser on biological tissue. The 755 nm alexandrite laser was expected to achieve better curative effect than the commonly used 585 or 595 nm pulsed dye laser (PDL) because of its deeper tissue penetration. In this study, the dorsal chamber model and microscopic visualization system were used to observe morphology changes on 42 blood vessels before and after irradiation with the 755 nm laser. Results showed that thermal effects of blood vessels intensified with the increase in energy, and high energy was required to produce the same thermal effect as the extension of pulse width. Different from 595 and 1064 nm lasers, partial vessel contraction was dominant thermal effect caused by the 755 nm laser. The bleeding injury rate and thermal effect of the 755 nm laser were between those of 595 nm PDL and 1064 nm Nd:YAG laser. The simulation results proved that 595 nm PDLs were effective for small and shallow target blood vessels. The 755 nm alexandrite lasers were effective in the treatment of hypertrophic and resistant blood vessels to PDL in the skin with low or moderate melanin concentration. The 1064 nm Nd:YAG laser was effective in the treatment of deeply buried and enlarged target blood vessels in the skin with high melanin concentration. The simulation results were supported by published clinical observations.

Targeting of prostate-specific membrane antigen for radio-ligand therapy of triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer has extremely high risk of relapse due to the lack of targeted therapies, intra- and inter-tumoral heterogeneity, and the inherent and acquired resistance to therapies. In this study, we evaluate the potential of prostate-specific membrane antigen (PSMA) as target for radio-ligand therapy (RLT). METHODS: Tube formation was investigated after incubation of endothelial HUVEC cells in tumor-conditioned media and monitored after staining using microscopy. A binding study with 68Ga-labeled PSMA-addressing ligand was used to indicate targeting potential of PSMA on tumor-conditioned HUVEC cells. For mimicking of the therapeutic application, tube formation potential and vitality of tumor-conditioned HUVEC cells were assessed following an incubation with radiolabeled PSMA-addressing ligand [177Lu]-PSMA-617. For in vivo experiments, NUDE mice were xenografted with triple-negative breast cancer cells MDA-MB231 or estrogen receptor expressing breast cancer cells MCF-7. Biodistribution and binding behavior of [68Ga]-PSMA-11 was investigated in both tumor models at 30 min post injection using µPET. PSMA- and CD31-specific staining was conducted to visualize PSMA expression and neovascularization in tumor tissue ex vivo. RESULTS: The triple-negative breast cancer cells MDA-MB231 showed a high pro-angiogenetic potential on tube formation of endothelial HUVEC cells. The induced endothelial expression of PSMA was efficiently addressed by radiolabeled PSMA-specific ligands. 177Lu-labeled PSMA-617 strongly impaired the vitality and angiogenic potential of HUVEC cells. In vivo, as visualized by µPET, radiolabeled PSMA-ligand accumulated specifically in the triple-negative breast cancer xenograft MDA-MB231 (T/B ratio of 43.3 ± 0.9), while no [68Ga]-PSMA-11 was detected in the estrogen-sensitive MCF-7 xenograft (T/B ratio of 1.1 ± 0.1). An ex vivo immunofluorescence analysis confirmed the localization of PSMA on MDA-MB231 xenograft-associated endothelial cells and also on TNBC cells. CONCLUSIONS: Here we demonstrate PSMA as promising target for two-compartment endogenous radio-ligand therapy of triple-negative breast cancer.

Vascular interventions in head and neck cancer patients as a marker of poor survival.

OBJECTIVE: Head and neck cancer can involve the surrounding vasculature and require technically challenging vascular interventions. These interventions can be complicated by tumor invasion, history of prior surgery, and history of radiation therapy. Our aim was to examine patients with vascular interventions in association with head and neck cancer to determine outcomes and best practice. METHODS: We performed a retrospective review of cancer patients treated by head and neck surgery and vascular surgery between 2007 and 2014. Data concerning previous cancer treatment, operative details of head and neck surgery and vascular surgery, perioperative outcomes, and survival data were collected. Statistical analyses were performed using the χ2 test, Student t-test, and binomial regression. Patency and survival data were determined by Kaplan-Meier analysis. RESULTS: A total of 57 patients with head and neck cancer requiring vascular interventions were identified. Of these, 44 patients had squamous cell carcinoma, 4 had thyroid cancer, 3 had sarcoma, 2 had Merkel and basal cell carcinoma, and 1 each had a parotid tumor, paraganglioma, extrarenal rhomboid tumor, and malignant spindle cell neoplasm. The majority of the interventions (n = 36 [63%]) were performed on patients with recurrent or persistent malignancy despite prior treatment. The most common previous treatment was radiation therapy (n = 44 [77%]). Tumor resection and vascular intervention were performed concurrently in 26 patients (46%). The mean time between cancer treatment and vascular intervention was 37 months (range, 18 days-18 years). The most common indication for vascular intervention was bleeding (n = 21 [37%]), which included vessel rupture (n = 14), tumor bleeding (n = 5), and intraoperative bleeding (n = 2). The remaining indications for intervention included invasion/encasement of major vasculature (n = 25), stenosis/occlusion (n = 12), and aneurysm (n = 1). The most common intervention was stenting (n = 22 [41%]), followed by resection (n = 20 [35%]), exposure/dissection (n = 12 [22%]), bypass (n = 8 [15%]), and embolization (n = 3 [6%]). Of the 22 patients who were stented, 12 (55%) were placed electively (11 for stenosis and 1 for aneurysm) and 10 (45%) were placed emergently (6 for blowout and 4 for tumor bleeding). A total of six patients (11%) required reintervention after their index vascular procedure. There were no intraoperative mortalities. The 30-day mortality was 9% (n = 5). The 30-day stroke rate was 7% (n = 4; one s/p common carotid artery-internal carotid artery bypass and three with emergent intervention for vessel rupture). Primary patency at 1 year was 66% for stents and 71% for bypass (P = .604). Survival in those patients operated on emergently for bleeding at 1 year was 38%, with a trend toward worse survival compared with the 77% survival at 1 year for all other indications (P = .109). The overall survival in the cohort at 1 and 2 years was 62% and 44%, respectively. CONCLUSIONS: Vascular involvement in head and neck cancer is a marker for poor survival. Any intervention performed in light of mass resection, persistent disease, and previous radiation complicates management. Minimally invasive techniques can be used with emergent bleeding but the survival benefits are marginal. Vascular interventions, including reconstruction, are feasible but should be approached with adequate expectations and multidisciplinary support.

Effect of internal mammary vessels radiation dose on outcomes of free flap breast reconstruction.

To assess the impact of internal mammary (IM) vessels radiation dose on autologous free-flap based breast reconstruction outcomes. We retrospectively evaluated the medical records of breast cancer patients who underwent mastectomy and free-flap breast reconstruction after postoperative radiation therapy (RT) to the breast/chest wall with (n = 9) or without (n = 11) electively including the IM lymph nodes. Twenty patients were included. Median age at diagnosis was 50 years (range, 33-63). The median time interval between the start of RT and reconstructive surgery was 16 months (range, 6-45). The maximal IM vessels dose was not associated with the risk of all complications (P = 0.44) or fat necrosis (P = 0.31). The mean IM vessels dose was not significant for the risk of all complications (P = 0.13) but was significant for fat necrosis (P = 0.04). A high mean IM vessels dose was related to the occurrence of fat necrosis.

Vascular Effects of Photodynamic Therapy with Curcumin in a Chorioallantoic Membrane Model.

Photodynamic Therapy (PDT) is a treatment that requires light, a photosensitizing agent, and molecular oxygen. The photosensitizer is activated by light and it interacts with the oxygen that is present in the cellular microenvironment. The molecular oxygen is transformed into singlet oxygen, which is highly reactive and responsible for the cell death. Therefore, PS is an important element for the therapy happens, including its concentration. Curcumin is a natural photosensitizer and it has demonstrated its anti-inflammatory and anti-oxidant effects that inhibit several signal transduction pathways. PDT vascular effects of curcumin at concentrations varying from 0.1 to 10 mM/cm² and topical administration were investigated in a chick Chorioallantoic Membrane (CAM) model. The irradiation was performed at 450 nm, irradiance of 50 mW/cm² during 10 min, delivering a total fluence of 30 J/cm². The vascular effect was followed after the application of curcumin, with images being obtained each 30 min in the first 3 h, 12 h, and 24 h. Those images were qualitatively and quantitatively analyzed with a MatLAB®. Curcumin was expected to exhibit a vascular effect due to its angio-inhibitory effect. Using curcumin as photosensitizer, PDT induced a higher and faster vascular effect when compared to the use of this compound alone.

Sepiapterin Enhances Tumor Radio- and Chemosensitivities by Promoting Vascular Normalization.

Previously, we demonstrated that nitric oxide (NO) synthase (NOS) is uncoupled in a wide range of solid tumors and that restoring NOS coupling with the tetrahydrobiopterin precursor sepiapterin (SP) inhibits tumor progression. Endothelial dysfunction characterizes the poorly functional vasculature of solid tumors, and since NO is critical for regulation of endothelial function we asked whether SP, by recoupling NOS, improves tumor vasculature structure and function-enhancing chemotherapeutic delivery and response to radiotherapy. MMTV-neu mice with spontaneous breast tumors were treated with SP by oral gavage and evaluated by multispectral optoacoustic tomographic analysis of tumor HbO2 and by tissue staining for markers of hypoxia, blood perfusion, and markers of endothelial and smooth muscle proteins. Recoupling tumor NOS activity results in vascular normalization observed as reduced tumor hypoxia, improved tumor percentage of HbO2 and perfusion, as well as increased pericyte coverage of tumor blood vessels. The normalized vasculature and improved tumor oxygenation led to a greater than 2-fold increase in radiation-induced apoptosis compared with radiation or SP alone. High-performance liquid chromatography analysis of tumor doxorubicin levels showed a greater than 50% increase in doxorubicin uptake and a synergistic effect on tumor cell apoptosis. This study highlights for the first time the importance of NOS uncoupling and endothelial dysfunction in the development of tumor vasculature and presents a new approach for improving the tumoricidal efficacies of chemotherapy and radiotherapy.

Glucose in Conjunction with Multiple Laser Pulses on Laser Treatment of Port-wine Stain: An in vivo Study.

Port-wine stain (PWS) birthmark is a congenital microvascular malformation of the skin. A 1064-nm Nd:YAG laser can achieve a deeper treatment, but the weak absorption by blood limits its clinical application. Multiple laser pulses (MLPs) are a potential solution to enhance the curative effect of a Nd:YAG laser. To reduce the pulse number (pn) required for the thermal destruction of the blood vessel, the effect of glucose in conjunction with MLP was investigated. In vivo experiments were performed on a dorsal skin chamber model. Different concentrations (20, 25, 30, and 40%) of glucose were applied to the sub-dermal side of the hamster skin before laser irradiation. Identical vessels with diameters of 200 ± 30 and 110 ± 20 µm were chosen as representatives of typical PWS vessels. Instant thermal responses of the blood vessel were recorded by a high-speed camera. The required pn for blood vessel damage was compared with that without glucose pretreatment. Results showed that the use of glucose with a concentration of 20% combined with MLP Nd:YAG laser to damage blood vessels is more appropriate because severe hemorrhage or carbonization easily appeared in blood vessels at higher glucose concentration of 25, 30, and 40%. When 20% glycerol is pretreated on the sub-dermal hamster skin, the required pn for blood vessel damage can be significantly decreased for different power densities. For example, pn can be reduced by 40% when the power density is 57 J/cm2. In addition, generation of cavitation and bubbles in blood vessels is difficult upon pretreatment with glucose. The combination of glucose with MLP Nd:YAG laser could be an effective protocol for reducing the pn required for blood vessel damage. Randomized controlled trial (RCT) and human trials will be conducted in the future.

Experimental and numerical investigation on the transient vascular thermal response to multi-pulse Nd:YAG laser.

BACKGROUND AND OBJECTIVE: Port wine stains (PWS) are congenital vascular malformations that progressively darken and thicken with age. Laser therapy is currently the most effective way in clinical practice for PWS. A 1,064 nm Nd:YAG laser in the near-infrared band can achieve a deeper treatment depth compared to the current widely adopted pulsed dye laser. However, because of its relatively weak absorption by blood, single-pulse Nd:YAG laser requires high energy density to cause effective vessel damage, but may inflict undesirable burning to surrounding collagen. Multi-pulse laser has great potential in clinical treatment because it needs less energy density for each pulse. This paper presented an experimental and theoretical study of the transient thermal effects of low-energy multi-pulse Nd:YAG laser on blood vessels. STUDY DESIGN/MATERIALS AND METHODS: In vivo experiments were performed on dorsal skin chamber. By using a high speed camera (up to 2,000 fps), the complete and dynamic thermal response of blood vessels during laser irradiation and between pulse intervals was obtained. In vitro experiment in capillary tubes and Numerical simulations by two-scale heat transfer model were also conducted to further explore the in vivo experimental findings. RESULTS: The complete and dynamic response of blood vessels were obtained, including vessel dilation, thrombus formation, partial vessel constriction, thread-like constriction, cavitation and bubbles, and hemorrhage. Thread-like constriction is the desirable treatment end point, which will only occur after thrombus completely occludes the vessel lumen. Cavitation can cause hemorrhage when thrombus fails to occlude the vessel lumen. In vitro experiment found that vessel constriction was due to the constriction of thrombus induced by laser irradiation. Theoretical investigation revealed that the mechanism for the effective reduction of energy density by multi-pulse Nd:YAG laser was due to enhanced light absorption of the blood with thrombus formation. CONCLUSIONS: For multi-pulse treatment, laser parameters are recommended as repetition rate of 10 Hz and pulse number of 10. The incident energy in each pulse should be strong enough to induce blood coagulation through seven or eight pulses and should be lower than the threshold of blood cavitation. Lasers Surg. Med. 49:852-865, 2017. © 2017 Wiley Periodicals, Inc.

Experimental investigation on the vascular thermal response to near-infrared laser pulses.

Port wine stains (PWS) are congenital vascular malformations that progressively darken and thicken with age. To improve the effect of laser therapy in clinical practice, thermal response of blood vessel to a 1064 nm Nd:YAG laser with controlled energy doses and pulse durations was evaluated using the dorsal skin chamber model. A total of 137 vessels with 30-300 µm diameters were selected from the dorsal skin of the mouse to match those capillaries in port wine stains. Experimental results showed that the thermal response of blood vessels to 1064 nm laser irradiation can be classified as follows: vessel dilation, coagulation, constriction with decreased diameter, complete constriction, hemorrhage, and collagen damage with increasing laser radiant exposure. In most cases, that is, 83 of 137 blood vessels (60.6%), Nd:YAG laser irradiation was characterized by complete constriction (immediate blood vessel disappearance). To reveal the possible damage mechanisms and evaluate blood vessel photocoagulation patterns, theoretical investigation using bioheat transfer equation was conducted in mouse skin with a depth of 1000 µm. Complete constriction as the dominant thermal response as evidenced by uniform blood heating within the vessel lumen was noted in both experimental observation and theoretical investigation. To achieve the ideal clinical effect using the Nd:YAG laser treatment, the radiant exposure should not only be high enough to induce complete constriction of the blood vessels but also controlled carefully to avoid surrounding collagen damage. The short pulse duration of 1-3 ms is better than long pulse durations because hemorrhaging of small capillaries is occasionally observed postirradiation with pulse durations longer than 10 ms.

Short-Term Choriocapillaris Changes in Patients with Central Serous Chorioretinopathy after Half-Dose Photodynamic Therapy.

BACKGROUND: Although photodynamic therapy (PDT) has become the standard treatment for central serous chorioretinopathy (CSC), its mechanism of action remains unclear. It is assumed that PDT induces short-term choriocapillaris (CC) occlusion and long-term choroidal vascular remodeling. In this paper, we describe the short-term CC changes induced by Half-Dose PDT (HD-PDT) in chronic CSC using optical coherence tomography-angiography (OCTA). METHODS: This is a prospective interventional case series. Chronic CSC eyes underwent Spectral-Domain OCT, Fundus Autofluorescence, FA, ICGA (Heidelberg Spectralis, Heidelberg, Germany) and OCTA (RTVue XR Avanti with AngioVue; Optovue Inc., Fremont, CA, USA) before HD-PDT, with follow-up after one hour, one week, and one month. Vascular changes after PDT were analyzed within the CC layer. The CC vessel density was defined as the percentage of an area occupied by flow pixels, using Image J software to obtain measurements by applying a grey level threshold. All pixels with a grey level above the threshold were considered as indicators of blood flow. RESULTS: 20 eyes of 19 patients were included. At baseline the mean CC vessel density was 94.87 ± 2.32%. It significantly differed from the density at 1 week and 1 month (92.79 ± 3.16% and 95.55 ± 2.05%, p < 0.001, respectively), but not with values at 1 h (94.8 ± 2.28%, p = 0.516). CONCLUSIONS: CC vessel density was significantly reduced at 1 week as compared with baseline, suggesting a possible short-term effect of PDT on CC perfusion. After 1 month however, the CC vessel density was even higher than the baseline, probably due to a CC recovery. OCTA seems to be useful in the visualization of CC vessels and in confirming the mechanism of action of PDT treatment in eyes with chronic CSC.

Vessel-sparing radiation and functional anatomy-based preservation for erectile function after prostate radiotherapy.

Treatment selection for men undergoing curative treatment for prostate cancer is often a challenging decision in view of the goal of maximising cure while maintaining quality of life. Previous quality-of-life comparisons suggest that specific outcomes are associated with type of treatment (surgery vs radiation); however, the functional anatomy approach, starting with nerve-sparing prostatectomy, assumes that quality-of-life outcomes are established by anatomic preservation. Emerging applications of the functional anatomy approach for prostate radiation will ultimately allow for individualised treatments that address the normal tissue variants visible on MRI. Such approaches will encompass all essential functions affected by treatment including genitourinary, rectal, and sexual functions. In this Review, we outline the current techniques in functional anatomy-based preservation related to sexual outcomes, and outline the capacity of vessel-sparing radiotherapy to preserve sexual function in 90% of patients at the 5 year follow-up while maintaining excellent cure rates.

Integrative proteomics and targeted transcriptomics analyses in cardiac endothelial cells unravel mechanisms of long-term radiation-induced vascular dysfunction.

Epidemiological data from radiotherapy patients show the damaging effect of ionizing radiation on heart and vasculature. The endothelium is the main target of radiation damage and contributes essentially to the development of cardiac injury. However, the molecular mechanisms behind the radiation-induced endothelial dysfunction are not fully understood. In the present study, 10-week-old C57Bl/6 mice received local X-ray heart doses of 8 or 16 Gy and were sacrificed after 16 weeks; the controls were sham-irradiated. The cardiac microvascular endothelial cells were isolated from the heart tissue using streptavidin-CD31-coated microbeads. The cells were lysed and proteins were labeled with duplex isotope-coded protein label methodology for quantification. All samples were analyzed by LC-ESI-MS/MS and Proteome Discoverer software. The proteomics data were further studied by bioinformatics tools and validated by targeted transcriptomics, immunoblotting, immunohistochemistry, and serum profiling. Radiation-induced endothelial dysfunction was characterized by impaired energy metabolism and perturbation of the insulin/IGF-PI3K-Akt signaling pathway. The data also strongly suggested premature endothelial senescence, increased oxidative stress, decreased NO availability, and enhanced inflammation as main causes of radiation-induced long-term vascular dysfunction. Detailed data on molecular mechanisms of radiation-induced vascular injury as compiled here are essential in developing radiotherapy strategies that minimize cardiovascular complications.

Effect of blood vessels on light distribution in optogenetic stimulation of cortex.

In this Letter, the impact of blood vessels on light distribution during photostimulation of cortical tissue in small rodents is investigated. Brain optical properties were extracted using a double-integrating sphere setup, and optical coherence tomography was used to image cortical vessels and capillaries to generate a three-dimensional angiogram of the cortex. By combining these two datasets, a complete volumetric structure of the cortical tissue was developed and linked to a Monte Carlo code which simulates light propagation in this inhomogeneous structure and illustrates the effect of blood vessels on the penetration depth and pattern preservation in optogenetic stimulation.

Phototoxicity of narrowband ultraviolet (UV) B (311 nm) compared with broadband UVB in the photo hen's egg test.

BACKGROUND: Broadband ultraviolet B (BB-UVB) is a well-established treatment option in dermatology. However, during the last decade BB-UVB has increasingly been replaced by narrowband UVB 311 nm (NB-UVB), especially in the therapy of psoriasis, atopic eczema and vitiligo. Several studies have indicated a better therapeutic response for almost all indications compared with BB-UVB. OBJECTIVES: The aim of our study was to investigate the phototoxic effects of NB-UVB in comparison with BB-UVB in vivo. METHODS: Therefore, we employed the photo hen's egg test (PHET), an established phototoxic model, based on the yolk sac blood vessel system of incubated hen's eggs. NB-UVB and BB-UVB dosages increasing from 30 up to 1200 mJ cm(-2) were applied on 17 test groups (each n = 12 eggs) and two unirradiated test groups served as controls. Twenty-four hours after irradiation we observed the following test parameters: lethality, membrane discoloration and haemorrhages. RESULTS: Following our results, the lethal half dose (LD50) was 60 and 720 mJ cm(-2) for BB-UVB and NB-UVB, respectively. These LD50 dosages provoked severe membrane discoloration and haemorrhaging. Summarizing our results, the LD50 of NB-UVB was 12-fold higher than BB-UVB. CONCLUSIONS: Interestingly, these findings are in good accordance with the literature, where the minimal erythema dose (MED) of NB-UVB in human skin is up to 14 times higher than the MED of BB-UVB. These results show that the PHET is a valid test model to evaluate the phototoxic effects of various UVB wavelengths. Moreover, our results indicate that regarding the investigation of phototoxic effects the PHET might serve as a model representative for human skin, which might reduce the extent of photoprovocation in humans in the future.

Experimental study on the vascular thermal response to visible laser pulses.

Port-wine stains (PWSs) are congenital vascular malformations that progressively darken and thicken with age, and laser therapy is the most effective in clinical practice. Using dorsal skin chamber (DSC), this study evaluated thermal response of blood vessel to a 595-nm pulsed dye laser (PDL) with controlled energy doses and pulse durations. Totally, 32 vessels (30∼300 µm in diameter) are selected from the dorsal skin of the mouse to match those in port-wine stain. The experimental results showed that the thermal response of the blood vessels to laser irradiation can be recognized as coagulation, constriction with diameter decrease, disappearance (complete constriction), hemorrhage, and collagen damage in the order of increasing laser radiant exposure. Blood vessels with small diameter would response poorly and survive from the laser heating because their thermal relaxation time is much shorter than the pulse duration. The optimalradiant exposure is from 10 to 12 J/cm(2) under 6 ms pulse duration without considering the epidermal light absorption. Numerical simulations were also conducted using a 1,000-µm deep Sprague-Dawley (SD) mouse skinfold. The light transportation and heat diffusion in dorsal skin were simulated with the Monte Carlo method and heat transfer equation, while the blood vessel photocoagulation was evaluated by Arrhenius-type kinetic integral. Both experimental observation and numerical simulation supported that hemorrhage is the dominant thermal response, which occurs due to preferential heating of the superior parts of large blood vessels. In clinical practice for 595 nm PDL, the consequent purpura caused by hemorrhage can be used as a treatment end point.