Pennes' bioheat equation vs. porous media approach in computer modeling of radiofrequency tumor ablation.

The objective of this study was to compare three different heat transfer models for radiofrequency ablation of in vivo liver tissue using a cooled electrode and three different voltage levels. The comparison was between the simplest but less realistic Pennes' equation and two porous media-based models, i.e. the Local Thermal Non-Equilibrium (LTNE) equations and Local Thermal Equilibrium (LTE) equation, both modified to take into account two-phase water vaporization (tissue and blood). Different blood volume fractions in liver were considered and the blood velocity was modeled to simulate a vascular network. Governing equations with the appropriate boundary conditions were solved with Comsol Multiphysics finite-element code. The results in terms of coagulation transverse diameters and temperature distributions at the end of the application showed significant differences, especially between Pennes and the modified LTNE and LTE models. The new modified porous media-based models covered the ranges found in the few in vivo experimental studies in the literature and they were closer to the published results with similar in vivo protocol. The outcomes highlight the importance of considering the three models in the future in order to improve thermal ablation protocols and devices and adapt the model to different organs and patient profiles.

Effects of nitrite and far-red light on coagulation.

Nitric oxide, NO, has been explored as a therapeutic agent to treat thrombosis. In particular, NO has potential in treating mechanical device-associated thrombosis due to its ability to reduce platelet activation and due to the central role of platelet activation and adhesion in device thrombosis. Nitrite is a unique NO donor that reduces platelet activation in that it's activity requires the presence of red blood cells whereas NO activity of other NO donors is blunted by red blood cells. Interestingly, we have previously shown that red blood cell mediated inhibition of platelet activation by adenosine diphosophate (ADP) is dramatically enhanced by illumination with far-red light that is likely due to photolysis of red cell surface bound NO congeners. We now report the effects of nitrite, far-red light, and their combination on several measure of blood coagulation using a variety of agonists. We employed turbidity assays in platelet rich plasma, platelet activation using flow cytometry analysis of a fluorescently labeled antibody to the activated platelet fibrinogen binding site, multiplate impedance-based platelet aggregometry, and assessment of platelet adhesion to collagen coated flow-through microslides. In all cases, the combination of far-red light and nitrite treatment decreased measures of coagulation, but in some cases mono-treatment with nitrite or light alone had no effect. Perhaps most relevant to device thrombosis, we observed that platelet adhesions was inhibited by the combination of nitrite and light treatment while nitrite alone and far-red light alone trended to decrease adhesion, but the results were mixed. These results support the potential of combined far-red light and nitrite treatment for preventing thrombosis in extra-corporeal or shallow-tissue depth devices where the far-red light can penetrate. Such a combined treatment could be advantageous due to the localized treatment afforded by far-red light illumination with minimal systemic effects. Given the role of thrombosis in COVID 19, application to treatment of patients infected with SARS Cov-2 might also be considered.

Radiation synergizes with antitumor activity of CD13-targeted tissue factor in a HT1080 xenograft model of human soft tissue sarcoma.

BACKGROUND: Truncated tissue factor (tTF) retargeted by NGR-peptides to aminopeptidase N (CD13) in tumor vasculature is effective in experimental tumor therapy. tTF-NGR induces tumor growth inhibition in a variety of human tumor xenografts of different histology. To improve on the therapeutic efficacy we have combined tTF-NGR with radiotherapy. METHODS: Serum-stimulated human umbilical vein endothelial cells (HUVEC) and human HT1080 sarcoma cells were irradiated in vitro, and upregulated early-apoptotic phosphatidylserine (PS) on the cell surface was measured by standard flow cytometry. Increase of cellular procoagulant function in relation to irradiation and PS cell surface concentration was measured in a tTF-NGR-dependent Factor X activation assay. In vivo experiments with CD-1 athymic mice bearing human HT1080 sarcoma xenotransplants were performed to test the systemic therapeutic effects of tTF-NGR on tumor growth alone or in combination with regional tumor ionizing radiotherapy. RESULTS: As shown by flow cytometry with HUVEC and HT1080 sarcoma cells in vitro, irradiation with 4 and 6 Gy in the process of apoptosis induced upregulation of PS presence on the outer surface of both cell types. Proapoptotic HUVEC and HT1080 cells both showed significantly higher procoagulant efficacy on the basis of equimolar concentrations of tTF-NGR as measured by FX activation. This effect can be reverted by masking of PS with Annexin V. HT1080 human sarcoma xenografted tumors showed shrinkage induced by combined regional radiotherapy and systemic tTF-NGR as compared to growth inhibition achieved by either of the treatment modalities alone. CONCLUSIONS: Irradiation renders tumor and tumor vascular cells procoagulant by PS upregulation on their outer surface and radiotherapy can significantly improve the therapeutic antitumor efficacy of tTF-NGR in the xenograft model used. This synergistic effect will influence design of future clinical combination studies.

Pharmacodynamics of romiplostim alone and in combination with pegfilgrastim on acute radiation-induced thrombocytopenia and neutropenia in non-human primates.

Purpose: Evaluation of the pharmacodynamics (PD) and pharmacokinetics (PK) of romiplostim alone and in combination with pegfilgrastim in a non-human primate (NHP) model of acute radiation syndrome (ARS).Materials and methods: Male and female rhesus macaques were subjected to Cobalt-60 γ irradiation, at a dose of 550 cGy 24 h prior to subcutaneous administration of either romiplostim alone as a single (2.5 or 5.0 mg/kg on Day 1) or repeat dose (5.0 mg/kg on Days 1 and 8), pegfilgrastim alone as a repeat dose (0.3 µg/kg on Day 1 and 8), or a combination of both agents (romiplostim 5.0 mg/kg on Day 1; pegfilgrastim 0.3 µg/kg on Days 1 and 8). Clinical outcome, hematological parameters and PK were assessed throughout the 45 d study period post-irradiation.Results: Administration of romiplostim, pegfilgrastim or the combination of both resulted in significant improvements in hematological parameters, notably prevention of severe thrombocytopenia, compared with irradiated, vehicle control-treated NHPs. The largest hematologic benefit was observed when romiplostim and pegfilgrastim were administered as a combination therapy with much greater effects on both platelet and neutrophil recovery following irradiation compared to single agents alone.Conclusions: These results indicate that romiplostim alone or in combination with pegfilgrastim is effective at improving hematological parameters in an NHP model of ARS. This study supports further study of romiplostim as a medical countermeasure to improve primary hemostasis and survival in ARS.

Carbon debris and fiber cleaving: Effects on potassium-titanyl-phosphate laser energy and chorioallantoic membrane model vessel coagulation.

OBJECTIVES/HYPOTHESIS: Photoangiolytic precision afforded by the 532-nm potassium-titanyl-phosphate (KTP) laser relies on predictable energy delivery. Inadequate energy output can cause vessel rupture, and excessive energy can cause thermal damage. The quality of the cleaved surface and carbon deposits from ablated tissue are two factors that could negatively impact fiber performance. The effects of these on energy output and blood vessel coagulation were assessed using a chorioallantoic membrane (CAM) model. STUDY DESIGN: Comparative analysis. METHODS: Laser fibers with carbon debris, optimal fiber cleaving, and suboptimal cleaving were inspected at three times magnification, and the light dispersion pattern of each fiber was rated. The average energy output from consecutive pulses through each fiber configuration was recorded. The effect of these fiber conditions on clinical efficacy was estimated by measuring vessel coagulation versus rupture in the CAM model. Repeated measures analysis of variance compared results. RESULTS: Carbon debris and suboptimal cleaving resulted in decreased energy output in comparison to optimal cleaving ([-Δ244 mJ, d = 4.31, P < .001] and [-Δ195 mJ, d = 6.04, P < .001]). Optimal cleaving resulted in immediate coagulation of vessels. Fibers with suboptimal cleaving and carbon debris had unpredictable outcomes, requiring multiple pulses for coagulation or causing vessel rupture. CONCLUSIONS: KTP laser fiber function is significantly affected by fiber tip condition. Carbon debris and suboptimal cleaving create significant attenuation of energy, which results in an unpredictable angiolytic effect, as demonstrated by increased vessel rupture in the CAM model. Optimal recleaving of KTP laser fibers restores prior energy output and predictable coagulation. Care should be taken to avoid carbon debris on laser-fiber tips and to cleave fibers properly. LEVEL OF EVIDENCE: NA Laryngoscope, 129:2244-2248, 2019.

Endothelial Microparticles and Blood Coagulation Activation in Head and Neck Cancer Patients Undergoing Radiotherapy or Radiochemotherapy.

BACKGROUND/AIM: Endothelial microparticles (EMP) are small vesicles which are released from the endothelium and contribute to blood coagulation activation in various clinical settings. The aim of this study was to examine whether EMP influence blood coagulation activation in cancer patients during radiotherapy/radiochemotherapy (RT/RCT). MATERIALS AND METHODS: Sixteen head and neck cancer (HNC) patients undergoing RT/RCT and 10 controls were examined. EMP and thrombin-antithrombin complex (TAT) were measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. Tissue factor-positive EMP (TF+EMP) were defined as CD31+/CD142+/CD42b- Results: TF+EMP were significantly elevated in HNC patients before RT/RCT (T0) (1299±1154/µl), one day after RT/RCT (T1d) (1257±603/µl) and 3 months after RT/RCT (T3m) (1289±372/µl) compared to controls (688±647/µl). TF+EMP levels at T0/T1d and T0, as well as at T1d and T3m were not significantly different. TAT levels at T0 and T1d did not differ significantly but at T3m were significantly lower compared to T0 and T1d TF+EMP and TAT concentrations were not significantly correlated at T0 (r=0.058; p=0.828), T1d (r=0.373, p=0.154) and T3m (r=-0.302, p=0.204). CONCLUSION: TF+EMP may not contribute to hemostatic abnormalities in HNC patients.

Coagulation parameters in hyperthyroid cats before and after radioiodine treatment compared with healthy controls.

OBJECTIVES: The aim of the study was to describe the coagulatory state of hyperthyroid cats before and after successful radioiodine therapy (RIT) compared with healthy age-matched controls, using classical coagulation parameters and thromboelastogram (TEG) as a global assessment method. The differences in coagulation activity after RIT, depending on the thyroid hormone (normal vs low total thyroxine [T4]) state, were also evaluated. METHODS: Fifteen hyperthyroid cats and 10 healthy age-matched controls were recruited. Hyperthyroid cats that remained hyperthyroid 14 days after RIT were excluded. Haematology, biochemistry, T4, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and TEG were assessed in control cats and hyperthyroid cats before and 7 and 14 days after RIT. Two weeks after successful RIT, further comparisons were made between cats with normal T4 vs those with low T4. RESULTS: Fourteen days after successful RIT, 7/15 cats had normal T4 and 8/15 had low T4. Thrombocytosis was noted in 6/15 cats after treatment. Fibrinogen was significantly higher (P <0.001) and PT shorter (P <0.01) in the hyperthyroid cats compared with the healthy controls and these changes persisted after RIT. Persistent increases in fibrinogen, PT, TEG maximal amplitude and TEG clot rigidity, reflecting clot stability, after RIT primarily occurred in the cats with normal T4. TEG-K (time until preset amplitude of 20 mm is reached) and alpha (α) angle reflected impaired fibrin cross-linking ability prior to RIT, which significantly increased after therapy (P <0.05). CONCLUSIONS AND RELEVANCE: Based on some of the coagulation parameters, cats with hyperthyroidism showed hypercoagulable tendencies, which were mildly increased after RIT, possibly due to transient radiation-induced thyroiditis.

Immediate laser-induced hemostasis in anticoagulated rats subjected to oral soft tissue surgery: a double-blind study.

Given the growing trend towards medical indications for continuous use of anticoagulants, the number of patients on these medications continues to rise. The management of patients on oral anticoagulants requiring oral surgical procedures has aroused much controversy. Changes in an anticoagulation regimen are associated with an increased risk of thromboembolism. However, it seems logical and advantageous for the patients' health if surgery could be performed without any change to the anticoagulation therapy. In dentistry, high-power lasers have been poorly explored in this field. The hemostatic properties of high-power lasers could be helpful during oral soft tissue surgeries in anticoagulated patients. The aim of this study was to compare bleeding time in anticoagulated rats after lingual frenectomy performed with a scalpel or diode laser with bleeding time in healthy animals. Twenty-four male Wistar rats were assigned to four groups (n = 6): (CS) Control-Scalpel Surgery; (AS) Anticoagulated-Scalpel Surgery; (CL) Control-Laser (diode laser 810 nm/1.5 W) Surgery; and (AL) Anticoagulated-Laser Surgery (diode laser 810 nm/1.5 W). Warfarin administration was used to induce anticoagulation. Blood was blotted every 30 seconds with filter paper until bleeding stopped to verify bleeding time. Two blinded researchers performed the surgeries and collected the bleeding time data. Diode laser surgery led to complete hemostasis in rats during and after lingual frenectomy. Zero bleeding was assessed during surgeries and after diode laser surgeries in anticoagulated rats. Laser-induced hemostasis offered an alternative solution to the controversial issue of intraoperative and postoperative bleeding control in patients on anticoagulation therapy.

Dual-wavelength-assisted thermal hemostasis for treatment of benign prostate hyperplasia.

Laser treatment on a large size of prostate gland often encounters significant bleeding that can prolong the entire procedure and cause urinary complications. The current study investigates the feasibility of dual-wavelength (532 and 980 nm) application to achieve rapid hemostasis for 532-nm laser prostatectomy. Porcine kidney and bleeding phantom models were tested to quantify the degree of the irreversible tissue coagulation and to estimate the time for the complete hemostasis, respectively. The ex vivo kidney testing verifies that the dual-wavelength created up to 40% deeper and 25% wider coagulation regions than a single wavelength does. The bleeding phantom testing demonstrates that due to the enhanced thermal effects, the simultaneous irradiation yields the complete photocoagulation (~11 seconds) whereas 532 or 980 nm hardly stops bleeders. Numerical simulations validate that the combined optical-thermal characteristics of both the wavelengths account for the augmented thermal coagulation. The dual-wavelength-assisted coagulation can be a feasible treatment to entail the rapid hemostasis and to facilitate the laser prostatectomy in an effective manner.

Immediate laser-induced hemostasis in anticoagulated rats subjected to oral soft tissue surgery: a double-blind study

Abstract Given the growing trend towards medical indications for continuous use of anticoagulants, the number of patients on these medications continues to rise. The management of patients on oral anticoagulants requiring oral surgical procedures has aroused much controversy. Changes in an anticoagulation regimen are associated with an increased risk of thromboembolism. However, it seems logical and advantageous for the patients' health if surgery could be performed without any change to the anticoagulation therapy. In dentistry, high-power lasers have been poorly explored in this field. The hemostatic properties of high-power lasers could be helpful during oral soft tissue surgeries in anticoagulated patients. The aim of this study was to compare bleeding time in anticoagulated rats after lingual frenectomy performed with a scalpel or diode laser with bleeding time in healthy animals. Twenty-four male Wistar rats were assigned to four groups (n = 6): (CS) Control-Scalpel Surgery; (AS) Anticoagulated-Scalpel Surgery; (CL) Control-Laser (diode laser 810 nm/1.5 W) Surgery; and (AL) Anticoagulated-Laser Surgery (diode laser 810 nm/1.5 W). Warfarin administration was used to induce anticoagulation. Blood was blotted every 30 seconds with filter paper until bleeding stopped to verify bleeding time. Two blinded researchers performed the surgeries and collected the bleeding time data. Diode laser surgery led to complete hemostasis in rats during and after lingual frenectomy. Zero bleeding was assessed during surgeries and after diode laser surgeries in anticoagulated rats. Laser-induced hemostasis offered an alternative solution to the controversial issue of intraoperative and postoperative bleeding control in patients on anticoagulation therapy.

Paediatric laser dentistry. Part 2: Hard tissue laser applications.

AIM: Erbium lasers can provide effective and minimally invasive caries removal in children. The bonding phase remains a critic step as well as the choice of material. Glass ionomers exhibits lower bonding properties in laser irradiated teeth compared to the conventional method or to composite and resin modified glass ionomer. Laser can also provide effective decontamination and coagulation effects in vital and non vital pulp therapy of primary teeth, improving and simplifying the cleaning and disinfecting steps.

Nd:YAG laser-induced morphology change and photothermal conversion of gold nanorods with potential application in the treatment of port-wine stain.

Based on the principle of selective photothermolysis, 1064 nm Nd:YAG laser has great potential for the treatment of deeper and larger PWS. However, the clinical effectiveness is limited because of the weak absorption of blood to Nd:YAG laser. The aim of this study is to obtain the optimal irradiation conditions to effectively destroy vascular lesions with the assistance of PEG-modified gold NRs to enhance blood absorption of Nd:YAG laser. In our study, PEG-modified gold NRs were prepared by the seeded growth method. Gold NRs after exposure to Nd:YAG laser were characterized using absorption spectra and transmission electron microscope images. The tissue-like phantom containing a glass capillary with blood was prepared and exposed to Nd:YAG laser to investigate the laser energy density and pulse number required for blood coagulation before and after the addition of gold NRs in blood. The results show that the millisecond Nd:YAG laser irradiation does not result in the shape change of gold NRs. After injection of gold NRs into the bloodstream (4.60 mg/kg), the absorbance of blood at 1064 nm increased 3.9 times. The threshold energy density for the treatment of PWS decreased by 33% (from 30 to 20 J/cm2). Our findings provide an experimental guide for choosing laser parameters and gold NRs concentration for the treatment of deeper and larger PWS with the assistance of PEG-modified gold NRs in vivo in the future.

Optical coherence tomography-guided laser microsurgery for blood coagulation with continuous-wave laser diode.

Blood coagulation is the clotting and subsequent dissolution of the clot following repair to the damaged tissue. However, inducing blood coagulation is difficult for some patients with homeostasis dysfunction or during surgery. In this study, we proposed a method to develop an integrated system that combines optical coherence tomography (OCT) and laser microsurgery for blood coagulation. Also, an algorithm for positioning of the treatment location from OCT images was developed. With OCT scanning, 2D/3D OCT images and angiography of tissue can be obtained simultaneously, enabling to noninvasively reconstruct the morphological and microvascular structures for real-time monitoring of changes in biological tissues during laser microsurgery. Instead of high-cost pulsed lasers, continuous-wave laser diodes (CW-LDs) with the central wavelengths of 450 nm and 532 nm are used for blood coagulation, corresponding to higher absorption coefficients of oxyhemoglobin and deoxyhemoglobin. Experimental results showed that the location of laser exposure can be accurately controlled with the proposed approach of imaging-based feedback positioning. Moreover, blood coagulation can be efficiently induced by CW-LDs and the coagulation process can be monitored in real-time with OCT. This technology enables to potentially provide accurate positioning for laser microsurgery and control the laser exposure to avoid extra damage by real-time OCT imaging.

[Impact of abdominal cavity open EHF irradiation on activity of adhesive process in peritonitis].

In experiment on 45 rats a purulent peritonitis was simulated. There was established, that on background of a standard therapy for peritonitis application of abdominal cavity open irradiation of extreme high frequency (EHF) have promoted rapid stabilization of the lipid metabolism indices and the blood coagulation system, the reduction of intensity of lipids peroxidal oxidation processes and severity of systemic inflammatory reaction. Under the influence of complex treatment the severity of adhesive process was reduced in 5.4 times, comparing with such in animals, to whom a standard treatment was conducted only. The revealed pathogenetic aspects of the adhesions formation witnesses the expediency to add EHF irradiation to complex therapy of peritonitis.

A safety study of a novel photosensitizer, sinoporphyrin sodium, for photodynamic therapy in Beagle dogs.

Sinoporphyrin sodium (DVDMS) is a novel hematoporphyrin-like photosensitizer developed for photodynamic therapy (PDT), an effective therapeutic modality for tumor treatment; however, the safety of photosensitizer-based PDT is always of great concern. The purpose of the current study was to investigate the potential repeated-dose toxicity and describe the toxicokinetic process of DVDMS-based PDT in Beagle dogs. The dogs were randomly allocated to six groups, and then were administrated a DVDMS preparation intravenously at dose levels of 0, 1, 3, 9, 1 and 9 mg per kg body weight, respectively; then, the latter two groups were illuminated 24 h later with a 630 nm laser for 10 min, once every seven days for 5 weeks. During the study period, clinical signs, mortality, body weight, food consumption, body temperature, ophthalmoscopy, hematology, serum biochemistry, urinalysis, electrocardiograms, toxicokinetics, organ weights, gross anatomy and histopathology were examined. After the administration, no deaths were observed; however, the dogs that received PDT showed skin swelling and ulceration, indicating that DVDMS-PDT induced a phototoxic effect. DVDMS led to an increase in blood coagulation in dogs in the 9 mg kg(-1) group and in the two PDT groups on Day 35, whereas it induced a decrease in dogs in the 3 mg kg(-1) group and in the two PDT groups on Day 49. The toxicokinetic study showed that the systematic exposure of DVDMS in dogs occurred in a dose-dependent manner, and DVDMS did not accumulate in blood plasma. The DVDMS-based PDT group showed no obvious treatment-related pathological changes; however, slight or mild brown-and-yellow pigmentation of DVDMS (or its metabolite) was observed to deposit in the liver, spleen, local lymph nodes and marrow of dogs in the mid- and high-dose groups, as well as the high-dose PDT group. In females, the absolute and relative spleen weights increased in dogs in the 9 mg kg(-1) DVDMS groups with and without PDT during the treatment and recovery period, respectively. The target organs are presumed to be the liver and immune organs (spleen, bone marrow and lymph nodes), while all of the responses were slight. Based on the results above, the no-observed-adverse-effect level (NOAEL) was considered to be 1 mg kg(-1), and DVDMS-PDT appeared to be a safe and promising anti-tumor therapy in the clinic.

Sonothrombolysis: the contribution of stable and inertial cavitation to clot lysis.

Microbubble-mediated sonothrombolysis (STL) is a remarkable approach to vascular occlusion therapy. However, STL remains a complex process with multiple interactions between clot, ultrasound (US), microbubbles (MB) and thrombolytic drug. The aim of this study was to evaluate the ability of combining US and MB to degrade fibrin and, more specifically, to assess the roles of both stable (SC) and inertial (IC) cavitation. Human blood clots containing radiolabeled fibrin were exposed to different combinations of recombinant tissue plasminogen activator (rtPA), US (1 MHz) and phospholipid MB. Three acoustic pressures were tested: 200, 350 and 1,300 kPa (peak-negative pressure). Clot lysis was assessed by diameter loss and release of radioactive fibrin degradation products. The combination rtPA + US + MB clearly revealed that IC (1,300 kPa) was able to enhance fibrin degradation significantly (66.3 ± 1.8%) compared with rtPA alone (51.7 ± 2.0%, p < 0.001). However, SC failed to enhance fibrin degradation at an acoustic pressure of 200 kPa. At 350 kPa, a synergistic effect between rtPA and US + MB was observed with an absolute increase of 6% compared to rtPA alone (p < 0.001). Conversely, without rtPA, the combination of US + MB was unable to degrade the fibrin network (0.3 ± 0.1%, p > 0.05 vs. control), but induced a distinct loss of red blood cells throughout the entire thickness of the clot, implying that MB were able to penetrate and cavitate inside the clot.

Shaken and stirred: mechanisms of ultrasound-enhanced thrombolysis.

The use of ultrasound and microbubbles as an effective adjuvant to thrombolytics has been reported in vitro, ex vivo and in vivo. However, the specific mechanisms underlying ultrasound-enhanced thrombolysis have yet to be elucidated. We present visual observations illustrating two mechanisms of ultrasound-enhanced thrombolysis: acoustic cavitation and radiation force. An in vitro flow model was developed to observe human whole blood clots exposed to human fresh-frozen plasma, recombinant tissue-type plasminogen activator (0, 0.32, 1.58 or 3.15 µg/mL) and the ultrasound contrast agent Definity (2 µL/mL). Intermittent, continuous-wave ultrasound (120 kHz, 0.44 MPa peak-to-peak pressure) was used to insonify the perfusate. Ultraharmonic emissions indicative of stable cavitation were monitored with a passive cavitation detector. The clot was observed with an inverted microscope, and images were recorded with a charge-coupled device camera. The images were post-processed to determine the time-dependent clot diameter and root-mean-square velocity of the clot position. Clot lysis occurred preferentially surrounding large, resonant-sized bubbles undergoing stable oscillations. Ultraharmonic emissions from stable cavitation were found to correlate with the lytic rate. Clots were observed to translate synchronously with the initiation and cessation of the ultrasound exposure. The root-mean-square velocity of the clot correlated with the lytic rate. These data provide visual documentation of stable cavitation activity and radiation force during sub-megahertz sonothrombolysis. The observations of this study suggest that the process of clot lysis is complex, and both stable cavitation and radiation force are mechanistically responsible for this beneficial bio-effect in this in vitro model.

Gelsolin: role of a functional protein in mitigating radiation injury.

The present study was conducted to explore the protective effect of exogenous gelsolin (GSN) in mice exposed to high-dose of radiation. Changes in the levels of GSNs in peripheral blood of mice and cytoplasm of cultured human intestinal epithelial cells (HIECs) were analyzed after their exposure to different doses of (137)Cs γ-rays at a fixed dose rate. The coagulation associated indices, such as prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured. Effect on radiation-mediated oxidative damage was evaluated by estimating the altered glutathione (GSH) and malondialdehyde (MDA) concentrations in the blood. The results showed that radiation induced a pronounced decrease in the pGSN blood levels. However, the cGSN levels of irradiated HIECs were increased in a dose-dependent manner. Administration of recombinant human pGSN to irradiated mice resulted in an ameliorated clotting time as indicated by the PT and the APTT indices. The treatment of mice with hpGSN enhanced the blood levels of GSH while MDA concentrations were decreased indicating an improved antioxidant status. These results suggest that GSNs might play a regulatory role in the suppression of the tissue damage induced by acute radiation exposure.

Laser-induced cavitation in nanoemulsion with gold nanospheres for blood clot disruption: in vitro results.

Optically activated cavitation in a nanoemulsion contrast agent is proposed for therapeutic applications. With a 56°C boiling point perfluorohexane core and highly absorptive gold nanospheres at the oil-water interface, cavitation nuclei in the core can be efficiently induced with a laser fluence below medical safety limits (70 mJ/cm2 at 1064 nm). This agent is also sensitive to ultrasound (US) exposure and can induce inertial cavitation at a pressure within the medical diagnostic range. Images from a high-speed camera demonstrate bubble formation in these nanoemulsions. The potential of using this contrast agent for blood clot disruption is demonstrated in an in vitro study. The possibility of simultaneous laser and US excitation to reduce the cavitation threshold for therapeutic applications is also discussed.

A basic fibroblast growth factor analog for protection and mitigation against acute radiation syndromes.

The effects of fibroblast growth factors and their potential as broad-spectrum agents to treat and mitigate radiation injury have been studied extensively over the past two decades. This report shows that a peptide mimetic of basic fibroblast growth factor (FGF-P) protects and mitigates against acute radiation syndromes. FGF-P attenuates both sepsis and bleeding in a radiation-induced bone marrow syndrome model and reduces the severity of gastrointestinal and cutaneous syndromes; it should also mitigate combined injuries. FGF-2 and FGF-P induce little or no deleterious inflammation or vascular leakage, which distinguishes them from most other growth factors, angiogenic factors, and cytokines. Although recombinant FGFs have proven safe in several ongoing clinical trials, they are expensive to synthesize, can only be produced in limited quantity, and have limited shelf life. FGF-P mimics the advantageous features of FGF-2 without these disadvantages. This paper shows that FGF-P not only has the potential to be a potent yet safe broad-spectrum medical countermeasure that mitigates acute radiotoxicity but also holds promise for thermal burns, ischemic wound healing, tissue engineering, and stem-cell regeneration.