Protective effects of Ecklonia cava extract on the toxicity and oxidative stress induced by hair dye in in-vitro and in-vivo models

Oxidative hair dyes containingρ-phenylenediamine(PPD)are reported to induce an allergic reaction by promoting oxidative stress when absorbed through the skin.Despite the associated risk,these hair dyes remain popular owing to their convenience and sharpness of color.This makes it important to minimize the cytotoxicity and oxidative stress induced by PPD-containing hair dyes.Ecklonia cava extract has been evaluated in different studies for its protective effects against external stress in fibroblasts and keratinocytes.Our study was aimed at using in-vitro and in-vivo models to investigate the extract’s effects on cytotoxicity of and oxidative stress induced by PPD-containing hair dyes.Analysis of CIEL*a*b*Color space was first used to determine the range of E.cava extract that would not interfere with the coloring ability of the dye upon addition.Subsequently,the set ranges of E.cava extract(5% and 7%)were added to the hair dye and their toxicity assessed by evaluating the viability of fibroblasts and keratinocytes.The effects on developmental phenotypes and induction of oxidative stress by hair dye were evaluated and compared with those of hair dyes containing different contents of E.cava extract using an in-vivo zebrafish model.Our results showed that E.cava extract in hair dye could significantly decrease the cytotoxicity and levels of oxidative stress caused by hair dyes containing PPD in both in-vitro and in-vivo models.These results suggest that the addition of 7% E.cava extract to 250μg/mL hair dye does not interfere with the coloring ability of the dye while showing significant protective eff ects against the hair dye.The study proposes that the use of E.cava extract as an adduct to hair dyes containing PPD reduces the cytotoxicity and oxidative stress induced by these hair dyes.

In-vitro and In-vivo Anti-trypanosomal Activity of Terminalia chebula Retz Dried Fruits

African trypanosomosis had caused lots of havocs to both humans and animals over a century with successes and failure in curtailing it. This study was aimed at screening medicinal plant, Terminalia chebula dried fruits against Trypanosoma evansi for trypanocidal activity. Twenty grams of powdered Terminalia chebula dried fruits was cold extracted with methanol. Obtained MPE （methanolic plant extract） was in vitro tested against Trypanosoma brucei （1 × 10^6 trypanosomes/mL of the medium in each ELISA plate wells） at concentrations （250～1,000 μg/mL） on Vero cells grown in DMEM （Debecco＇s Modified Eagle Medium） in appropriate conditions for trypanocidal activity. In-vitro cytotoxicity test of MPE of Terminalia chebula was conducted on Vero cells grown in DMEM. In-vivo assay for trypanocidal activity, each mouse was inoculated with 1 × 10^4/mL of trypanosomes and treated （48 h post inoculation） with MPE of Terminalia chebula at concentrations （12.5, 25, 50, 100 and 200 mg/kg body weight） were administered at dose rate of 100 BL per mouse via intraperitoneal route to different groups of mice, 6 mice per concentration. In-vitro cytotoxicity test was done on Veto cells at concentrations （1.58～100 μg/mL） of MPE of Terminalia chebula. Results of in-vitro trypanocidal activity varied from immobilization, reduction and to the killing of the trypanosomes. At 250 μg/mL ofMPE ofTerminalia chebula dried fruits, there was significant trypanocidal activity at 4 h of incubation and trypanosomes were not detected in corresponding ELISA plate wells at 5 h of incubation, which was statistically equivalent to reference drug, diminazine aceturate （50 μL/mL） at 4 h of incubation. Results of in-vivo trypanocidal activity revealed that at concentrations （l 2.5～25 mg/kg body weight） of MPE of Terrninalia chebula, mice in these groups survived for 6 days. While at 50 and 100 to 200 mg/kg body weight, mice in these groups survived up to 7 and 8 days, respectively. In-vitro cytotoxicity test showed that all concentrations of MPE of Terminalia chenula and diminazine aceturate were cytotoxic to cells except at 1.56 μL/mL and 6.25 μL/mL. In conclusion, MPE of Terminalia chebula dried fruits possessed trypanocidal compounds. Further study （bioassay-guided purification） is required to know the full potential of Terrninalia chebula as future trypanocide candidate.

Position Verification of the RADPOS 4-D <i>In-Vivo</i>Dosimetry System

The accuracy of the position measurements obtained by the radiation positioning system (RADPOS) was evaluated under static and dynamic conditions. In the static verifications, the RADPOS was fixed to the treatment couch in a photon treatment room and a proton treatment room, and was translocated with the treatment couch in x, y and z directions. Because the presence of magnetic and/or electrically conductive materials can cause a systematic shift in the measured position by distorting the RADPOS transmitted field, the effect of metals on the performance of the positioning system was also investigated. Dynamic verification was performed using the couch drive and a dynamic anthropomorphic thorax phantom. We thus confirmed the utility of RADPOS as a position sensor to perform in vivo dosimetry.

Mathematical Modelling of In-Vivo Dynamics of HIV Subject to the Influence of the CD8+ T-Cells

There have been many mathematical models aimed at analysing the in-vivo dynamics of HIV. However, in most cases the attention has been on the interaction between the HIV virions and the CD4+ T-cells. This paper brings in the intervention of the CD8+ T-cells in seeking, destroying, and killing the infected CD4+ T-cells during early stages of infection. The paper presents and analyses a five-component in-vivo model and applies the results in investigating the in-vivo dynamics of HIV in presence of the CD8+ T-cells. We prove the positivity and the boundedness of the model solutions. In addition, we show that the solutions are biologically meaningful. Both the endemic and virions- free equilibria are determined and their stability investigated. In addition, the basic reproductive number is derived by the next generation matrix method. We prove that the virions-free equilibrium state is locally asymptotically stable if and only if R0 < 1 and unstable otherwise. The results show that at acute infection the CD8+ T-cells play a paramount role in reducing HIV viral replication. We also observe that the model exhibits backward and trans-critical bifurcation for some set of parameters for R0 . This is a clear indication that having R0 is not sufficient condition for virions depletion.

<i>In-Vivo</i>Dosimetry Method for Measuring Peak Surface Dose Using Radiochromic Films during Computed Tomography Scanning of the Sinus

Purpose: During computed tomography (CT) helical scanning mode the patient surface dose distribution is assumed to be non-uniform, therefore point dose measurement methods may lead to imprecise estimation of the radiation dose received by the patient skin in particular. We have used XRQA2 films as in-vivo dosimeters to measure the entrance skin dose during sinus exams. Methods: The films were placed under the patient head rest in order to sample the entrance surface dose in-vivo. We have performed in-vivo film irradiation on 23 patients in this study to verify the clinical suitability of the method and were found adequate. Results: The measured average ESD in the sinus exam was 11.7 ± 1.0 mGy, the PSD was 15.7 ± 1.7 mGy and the CTDI(vol) was 13.3 ± 0.1 mGy. The ratio of ESD/CTDI(vol) and PSD/CTDI(vol) was 0.88 and 1.18 respectively. The results indicate that the scanner registered CTDI(vol) underestimates the PSD and in the same time it overestimates the ESD by 18% and 13.6% respectively. Conclusion: The observed differences between the ESD, PSD and CTDI(vol) although seem small for the radiation dose range measured during CT of the sinus [13.2 - 13.4] mGy, but important for the medical physicist to know, since monitoring of patients’ doses from CT examinations is becoming more mandatory. The use of radiochromic film as in-vivo dosimeter does not interfere with the clinical radiological exam and does not produce any image artifacts. The method can be used to study other CT examinations specially the ones with large beam width, high pitch factor and high dose exams. The method allows measurement of the peak skin dose, examination of the CT dose profile and the 2D dose distribution in the XZ plan.

Inter-Fraction and Intra-Fraction Variation in the Absorbed-Dose Delivery during Interstitial High Dose Rate Brachytherapy—A Study Using MicroMOSFET <i>In-Vivo</i>Dosimeter

Background: The delivered dose has to be checked and verified with planned dose since precise and accurate dose delivery is essential in Brachytherapy. Sources of uncertainty during Brachytherapy are intra-fraction, inter-fraction and inter-application variations. In-vivo dosimetry is the direct method to monitor the radiation dose delivered to a patient during radiotherapy. In this study, assessment of the inter-fraction and intra-fraction variations in the interstitial Brachytherapy was done with microMOSFET. Aim: To analyze the inter-fraction variations in dose delivery during interstitial HDR Brachytherapy and to compare the measured point dose with the TPS-calculated point dose, intra-fraction variation, using the microMOSFET in-vivo dosimeter. Materials and Methods: From May 2014 to February 2016, 22 patients with Head and Neck cancers and 8 patients with Soft-Tissue Sarcomas (STS) were selected for this study. All these patients underwent CT imaging more than 24 hours after the application. Brachyvision 3DTPS and GammaMed Plus iX HDR unit were used for treatments. MicroMOSFET in-vivo dosimeter after calibration was used for the measurements of dose inside the treated volume. Intra & Inter-fraction variations were analyzed and reported. Results: The SD of inter-fraction variation among 22 Head & Neck patients ranges from 2.14% to 14.26%. Minimum & maximum dose variation with first fraction dose of patients ranged from -22.33% to +26.71% and the mean doses were -6.42% to +19.76%. Differences of TPS dose and microMOSFET measured first fraction dose, intra-fraction variation, ranged from -12.36% to +5.05%. The SD of inter-fraction variation for 8 STS patients was from 2.81% to 14.43%. Minimum and maximum doses vary from -38.72% to +25.74% and mean dose varies from -21.5% to +12.53%. Differences of point doses of TPS and measured, intra-fraction variation, were from -5.86% to 4.88%. Conclusions: MicroMOSFET has the potential to minimize the gross errors during multi-fractionated Interstitial Brachytherapy. Edema, applicator displacements and placement of microMOSFET are the main influencing factors for inter-fraction uncertainty in dose delivery. Re-planning with re-simulated images should be considered whenever the microMOSFET readings vary more than ±10% of the planned dose inside the CTV measured in two successive fractions.

An <i>In-Vivo</i>Study during Combined Intracavitary and Interstitial Brachytherapy of Gynaecological Malignancies Using microMOSFET

Aim: To analyze the inter-fraction, intra-fraction uncertainties and to verify the delivered total dose with planned dose in the combined intracavitary-interstitial brachytherapy of gynaecological cancer patients using microMOSFET in-vivo dosimeter. Materials and Methods: Between May 2014 and March 2016, 22 patients who underwent brachytherapy treatments with an applicator combination of CT/MR compatible tandem, ring and Syed-Neblett template-guided rigid needles were included in this study. Specially designed microMOSFET, after calibration, was used to analyze the variations in dosimetry of combined intracavitary-interstitial application. Results: The standard deviation for Inter-fraction variation among 22 combined intracavitary interstitial applications ranged between 0.86% and 10.92%. When compared with the first fraction dose, the minimum and maximum dose variations were &minus;9.5% and 26.36%, respectively. However, the mean doses varied between &minus;5.95% and 14.49%. Intra-fraction variation, which is the difference of TPS calculated dose with first fraction microMOSFET-measured dose ranges from &minus;6.77% to 8.68%. The variations in the delivered total mean dose in 66 sessions with planned doses were &minus;3.09% to 10.83%. Conclusions: It is found that there was a gradual increase in microMOSFET measured doses as compared to the first fraction with that of subsequent fractions in 19 out of 22 applications. Tumor deformation and edema may be the influencing factors, but the applicator movements played a major role for the variations. We find that the microMOSFET is an easy and reliable system for independent verification of uncertainties during ICBT-ISBT treatments.

A Consensus Modeling Approach for the Determination of Stratum Corneum Thickness Using In-Vivo Confocal Raman Spectroscopy

The measurement of stratum corneum (SC) thickness from in-vivo Raman water concentration depth profiles is gaining in popularity and appeal due to the availability and ease of use of in-vivo confocal Raman measurement systems. The foundation of these measurements relies on high-quality confocal Raman spectroscopy of skin and the robust numerical analysis of water profiles, which allow for accurate determination of SC thickness. These measurements are useful for studying intrinsic skin hydration profiles at different body sites and for determining hydration properties of skin related to topically applied materials. While the use of high-quality in-vivo Raman instrumentation has become routine and its use for SC thickness measurement widely reported, there is lack of agreement as to the best method of computing SC thickness values from Raman water profiles. Several methods have been proposed and are currently in use for such computations, but none of these methods has been critically evaluated. The work reported in this paper describes a new method for the determination of stratum corneum thickness from in-vivo confocal Raman water profiles. The method represents a consensus approach to the problem, which was found necessary to apply in order to properly model and quantify the large diversity of water profile types encountered in typical in-vivo Raman water measurement. The methodology is evaluated for performance using three criteria: 1) frequency of minimum fitting error on modeling to a standard numerical function;2) frequency of minimum model error for consensus vs. individual SC thickness values;and 3) correlation with reflectance confocal microscopy (RCM) values for SC thickness. The correlation study shows this approach to be a reasonable replacement for the more tedious and time-consuming RCM method with R2 = 0.68 and RMS error = 3.7 microns over the three body sites tested (cheek, forearm and leg).

Production of porous Ni-Ti alloy and test of its biocompatibility under in-vivo conditions

Biomaterials have been out of commonly used materials in biomedical applications in recent years. Today among the mostly-used biocompatible metals are especially Ni-Ti alloys. For conducting this study, having extensive usage area in biomedical applications, Ni and Ti materials were utilized for an alloy production. Following being mixed using a suitable mixer at 49Ni/51Ti %wt., the alloy was exposed to cold pressure of 200 MPa and sintered in a mold. In addition, the material gained porosity appearance thanks to usage of the synthesized (SHS) method and then the final shape of the specimen was taken using the method of wire electro erosion discharge machining (WEDM). Afterwards, the specimen was subjected to the biocompatibility test in in-vivo environment by means of on a 3-year-old female dog.

Biomimetic Hydroxyapatite Coated Titanium Screws Demonstrate Rapid Implant Stabilization and Safe Removal In-Vivo

The early fixation of bone screws after surgical implantation still remains a challenge in the field of traumatology. Whilst hydroxyapatite (HA) coatings are known to enhance the fixation of implants;their removal at a later time-point may be problematic. An HA coating has been developed to demonstrate that both implant fixation and safe removal are feasible in the same design. Accordingly the aim of this study was to compare the In-Vivo performance of thin biomimetic HA coated titanium screws to uncoated counterparts used as control after bilateral implantation in the femoral condyle of 36 New Zealand White Rabbits. The screws were analysed macroscopically, by histology, micro-CT and biomechanically at both two and six weeks post-implantation. The HA coated screws demonstrated excellent biocompatibility. At two weeks the HA coated screws demonstrated a significant increase in removal torque values as well as a strong trend towards higher pull-out forces. In addition histology confirmed a higher degree of osseointegration and direct bone to implant contact. At six weeks no difference in pull-out force and removal torque could be detected. SEM images confirmed the absence of any residual HA coating indicating a fast coating degradation In-Vivo. The low level of removal torque after full osseointegration at 6 weeks supports the feasibility of safe and easy removal of the implant. The HA coating under study appears to offer a unique characteristic of enhanced fixation with a minimal increase in removal torque after full osseointegration. This may be of value in clinical applications where it is necessary to assure both screw fixation and later removal.

Dual-Fields Rotational Total Skin Electron Therapy: Investigation and Implementation

Purpose: To present a protocol of a dual-field rotational (DFR) total skin electron therapy (TSET) and to provide an assessment of clinical implementation, dosimetry properties, and skin dose evaluation. Methods and Materials: The DFR-TSET combined the Stanford 6-field and McGill rotational methods. Dual 6 MeV electron beams in high dose total skin electron mode were used for DFR-TSET on a commercial linac. Beam profiles and dosimetric properties were measured using solid phantoms. The dose rate at expanded source-to-surface distance (SSD) was a combination of static rate and rotational rate. In vivo dosimetry of patient skin was performed on patients’ skin using film, metal oxide semiconductor field-effect transistors (MOSFET), and optically stimulated luminescent dosimeters (OSLD). Results: Dual field rotational total skin electron therapy exhibited good (≤±10%) uniformity in the beam profiles in the vertical direction at an extended SSD of 332 cm with a gantry angulation of ±20˚ deviated from the horizontal direction. In-vivo measurements confirmed acceptable uniformity of the patients’ total body surfaces and revealed anatomically self-blocked or shielded areas where underdosing occurred. Conclusions: The clinical implementation of DFR-TSET effectively utilizes the special mode on a linac. This technique provides short beam-on times, uniform dose distribution, large treatment field, and reduced dose of x-ray contamination to the patients. In-vivo measurements indicate satisfactory delivery and dose uniformity of the prescribed dose. Electron boost fields are recommended at normal SSDs to address underdosed areas.

Growth regulation of luminescent gold nanoparticles directed from amphiphilic block copolymers:highly-controlled nanoassemblies toward tailored in-vivo transport

The understanding of amphiphilic block copolymers(ABC)in encapsulation and transport of inorganic nanomedicines is highly desired.Still,it remains limited due to the challenges in the fabrication of nanoassemblies(NAs)with highly-controlled shape and loading of nanoparticles.Herein,through growth regulation of luminescent gold nanoparticles(Au NPs)by different reductants with ABC pluronic F127 as a template,a straightforward strategy is reported for in-situ fabrication of three wellcontrolled gold NAs(Au NAs)that display tunable shapes from spherical to elongated nanostructures and controllable surface chemistry and loading of Au NPs with distinct emissions but identical individual Au NP size.The three Au NAs exhibit tailored invivo transport behaviours:those with spherical shape and more hydrophilic surface show longer blood retention with higher tumor-targeting efficiency(~25.3%injection dose/g)and excellent long-term near-infrared tumor imaging even after 96 h postinjection.These findings provide a useful guidance in designing specific nanostructures for future nanomedicine transport.

Deciphering In-vivo Cross-linking Mass Spectrometry Data for Dynamic Protein Structure Analysis

Protein structure and protein-protein interactions(PPIs)are crucial for regulating cellular activities required for cell viability and homeostasis.Chemical cross-linking coupled with mass spectrometry(CXMS)has become a versatile tool providing insights into both protein structure with distance restraints and protein-protein interactions with interface sites.Cross-links as the most information-rich data in a CXMS experiment are responsible for the structural model validation and integrative modeling with high throughput and sensitivity.In this work,ensemble refinement of the existing protein structure against the in-vivo cross-linking distance restraints was performed for dynamic protein structure modeling and protein interaction binding interface building in the intracellular environment.These results indicate great potential of in-vivo CXMS data for providing a molecular basis of protein structural dynamics exploration and function performance.

In-vivo proton range verification for reducing the risk of permanent alopecia in medulloblastoma treatment

Objective:The purpose of this work is the clinical commissioning of a recently developed in-vivo range verification system for the head treatment of pediatric medulloblastoma patients.Inaccurate beam range for such treatment could lead to either inadequate dose coverage of the target volume or excessive dose to the head skin resulting permanent alopecia.Methods:The in-vivo range verification system is designed to perform pre-treatment range verification and adjustment.An array of Si-diode detectors is to be placed on the patient immobilization mask in the exit direction of a whole-brain field;signal is analyzed,and the extracted water equivalent path length(WEPL)is compared to the expected one,revealing if a range correction is needed.The method was tested in solid water and anthropomorphic head phantom,with validation based on independent WEPL measurements.The measured WEPL were compared to those computed by the treatment planning system(TPS).Results:The accuracy for the WEPL measurements by the diode system in both solid water and anthropomorphic head phantom were on average within a millimeter from more accurate measurement by the dose-extinction technique,with the error range for the two phantoms as(0–1 mm)and(0–1.3 mm),respectively.When compared to the WEPL calculated by the treatment planning system,the measured values were on average within 1%(range 0–3%)of the beam range.The accuracy of dose measurements by the diodes in the fall-off part of the depth dose profile was validated against the reference Markus chamber.No need for further correction(due to different beam parameters and detector dose ageing effects)was found.Conclusions:The range verification workflow was successfully tested in the anthropomorphic head phantom.The performance of the in-vivo range verification system and related workflow meet the clinical requirements in terms of the needed WEPL accuracy for pretreatment range verification.

Polymeric bilayer modified microelectrodes for in-vivo determination of neurotransmitter dopamine

A composite polymer carbon fiber electrode modified with Nafion and cellulose acetate is described. The modified electrode discriminates against both anionic reactants and big molecular organic compounds. The bilayer configuration is prepared in two steps. First, the carbon fiber electrode is coated with Nation, men followed by air evaporation of the solvent, me electrode is dipped in a cellulose acetate solution and hydrolyzed for a selected time. The permeability of the film is explored by use of rotating disk electrode measurements. Parameters affecting the film electrochemistry are investigated. The resulting electrodes show high selectivity and stability in body fluids. For in-vivo voltammetry, the composite polymer modified electrode has been used for detection of me oxidative current of neurotransmitter dopamine in rat brain, while it inhabits the oxidation of an°C neurotransmitter metabolites and some electroactive compounds.

Detection of cells by flow cytometry:Counting,imaging,and cell classification

The study of circulating cells in the blood stream is critical,as it covers many felds of biomed-icine,including immunology,cell biology,oncology,and reproductive medicine.In-viuo flowcytometry(IVFC)is a new tool to monitor and count cells in real time for long durations in theirnative biological environment.This review describes two main categories of IVFC,ie.,labeledand label-free IVFC.It focuses on label-free IVFC and introduces its technological developmentand related biological applications.Because cell recognition is the basis of flow cytometrycounting,this review also describes various methods for the classification of unlabeled cells,including the latest machine learning-based technologies.

A review of effective strides in amelioration of the biocompatibility of PEO coatings on Mg alloys

Recently,developing bioactive and biocompatible materials based on Mg and Mg-alloys for implant applications has drawn attention among researchers owing to their suitable body degradability.Implementing Mg and its alloys reduces the risk of long-term incompatibility with tissues because of their close mechanical properties and no need for re-operation to remove the implant.Nevertheless,the degradation rate of the implant needs to be controlled because production of hydrogen gas and accumulation of its bubbles increases local pH around the implants.To confine the integrity of implants and the body,the corrosion concern in the body fluid requires to be addressed.Surface modification as one of the effective strategies can improve corrosion resistance.Besides,it creates a suitable surface for bone grafting and cell growth.The development of proper surface-coated implants needs appropriate techniques and approaches.Plasma electrolytic oxidation(PEO)coating can provide long-term protection by providing a ceramic layer and improving the implant’s biocompatibility.Herein,a general review of in-vivo and in-vitro evaluation of PEO coatings on Mg and Mg-alloys has been carried out.Recent advances in surface modification on Mg and Mg-alloys have been discussed,however,the need for reliable laboratory models to predict in-vivo degradation is still valid.

Segmental Kinematic Coupling of the Human Spinal Column during Locomotion

As one of the most important daily motor activities, human locomotion has been investigated intensively in recent decades. The locomotor functions and mechanics of human lower limbs have become relatively well understood. However, so far our understanding of the motions and functional contributions of the human spine during locomotion is still very poor and simultaneous in-vivo limb and spinal column motion data are scarce. The objective of this study is to investigate the delicate in-vivo kinematic coupling between different functional regions of the human spinal column during locomotion as a stepping stone to explore the locomotor function of the human spine complex. A novel infrared reflective marker cluster system was constrncted using stereophotogrammetry techniques to record the 3D in-vivo geometric shape of the spinal column and the segmental position and orientation of each functional spinal region simultaneously. Gait measurements of normal walking were conducted. The preliminary results show that the spinal column shape changes periodically in the frontal plane during locomotion. The segmental motions of different spinal functional regions appear to be strongly coupled, indicating some synergistic strategy may be employed by the human spinal column to facilitate locomotion. In contrast to traditional medical imaging-based methods, the proposed technique can be used to investigate the dynamic characteristics of the spinal column, hence providing more insight into the functional biomechanics of the human spine.

Two-Photon Absorption Properties of Mn-Doped ZnS Quantum Dots

We investigate the two-photon absorption and nonlinear refractive index properties of a quantum dot material based on ZnS nanocrystals doped with Mn isoelectronic impurities, using the Z-scan technique with 532nm picosecond laser pulses. The Mn-doped ZnS quantum dots have an average two-photon absorption cross section as high as 13600 Goeppert-Mayer units, which turn it into a very promising material for fluorescent label and imaging in biological samples. In addition, we also found that the two-photon absorption coefficient initially increases and then decreases with increasing pulse irradiance, which demonstrates the presence of the higherorder nonlinearity under the strong excitation.