Mitigation of epidermal growth factor receptor inhibitor-induced side effects utilizing melanin and vascular-specific lasers: A case report series.

The advent of targeted chemotherapy has led to the emergence of new dermatologic toxicities. We sought to use lasers and light devices to treat recalcitrant cutaneous adverse effects related to cancer treatment. Three stage III or IV cancer patients with cutaneous complications due to epidermal growth factor receptor (EGFR) inhibitors were treated with melanin and vascular-specific laser and light technologies. Two patients reported reduction in papulopustular eruption following pulse dye laser (PDL) treatment. Two patients noted reduction in hair growth following intense pulsed light (IPL) and/or Alexandrite laser treatments. One patient was treated with both the PDL and IPL and reported improvement of both EGFR-induced hypertrichosis and papulopustular eruption. Laser and light devices targeting melanin and hemoglobin can be utilized to mitigate the cutaneous adverse effects associated with EGFR inhibitors in patients who have failed traditional therapies. This represents a new option for the cancer patient who is suffering from chemotherapy-induced side effects.

Dynamic optical absorption characteristics of blood after slow and fast heating.

Laser treatment is the most effective therapy in dermatology for vascular skin disorders, such as port-wine stains (PWS). Changes in heat-induced absorbance in blood must be determined for accurate numerical simulation and implementation of multi-pulse laser therapy for treatment of PWS. Thermally induced absorbance changes in hemoglobin in blood were compared in vitro between slow water bath heating and fast heating irradiated by using sub-millisecond Nd:YAG laser. Blood composition at different temperatures was calculated by comparing blood absorption spectra with those of pure HbO2, Hb, and metHb at room temperature. Blood absorbance to heat energy were categorized into three stages distinguished by metHb and coagulation points, which are the validity and security thresholds of the optimized therapy, respectively. Rapid laser heating can distinctively enhance blood absorbance by photochemically induced strong instability compared with slow heating at a constant temperature. Slow heating facilitates metHb point at 70 °C and coagulation point at 75 °C as the temperature of the water bath increases. However, the temperature at which metHb or coagulation point shifts to higher than 10 °C when pulses and fluence in laser irradiation change. Laser fluence less than 20 J/cm2 and more than 50 J/cm2 is unsuitable for laser treatment because of its low probability to coagulate vascular hyperplasia and high probability to damage normal tissues adjacent to target lesions, respectively. Few bubbles formed after mediate fluence is beneficial to minimize adverse side-effects. Considering blood absorbance, temperature evolution, and bubble formation, we recommend 30-40 J/cm2 and 2-4 Hz frequency as the optimal laser parameters in sub-millisecond Nd:YAG laser.

Differential sensitivity of Chironomus and human hemoglobin to gamma radiation.

Chironomus ramosus is known to tolerate high doses of gamma radiation exposure. Larvae of this insect possess more than 95% of hemoglobin (Hb) in its circulatory hemolymph. This is a comparative study to see effect of gamma radiation on Hb of Chironomus and humans, two evolutionarily diverse organisms one having extracellular and the other intracellular Hb respectively. Stability and integrity of Chironomus and human Hb to gamma radiation was compared using biophysical techniques like Dynamic Light Scattering (DLS), UV-visible spectroscopy, fluorescence spectrometry and CD spectroscopy after exposure of whole larvae, larval hemolymph, human peripheral blood, purified Chironomus and human Hb. Sequence- and structure-based bioinformatics methods were used to analyze the sequence and structural similarities or differences in the heme pockets of respective Hbs. Resistivity of Chironomus Hb to gamma radiation is remarkably higher than human Hb. Human Hb exhibited loss of heme iron at a relatively low dose of gamma radiation exposure as compared to Chironomus Hb. Unlike human Hb, the heme pocket of Chironomus Hb is rich in aromatic amino acids. Higher hydophobicity around heme pocket confers stability of Chironomus Hb compared to human Hb. Previously reported gamma radiation tolerance of Chironomus can be largely attributed to its evolutionarily ancient form of extracellular Hb as evident from the present study.

Functional Features of Microcirculation System and its Possibilities of Oxygen Transport in Children and Youths of Bryansk Region in Conditions of Radioecological Pressure.

The questions of influence of low radiation doses on microcirculation of blood in ontogeny of males from 7 to 27 years are presented in the article. Using the method of laser Doppler ultrasounds, optical oximetry and laser fluorescent diagnostics, we studied the blood perfusion level in the microcirculation system of 315 schoolchildren and students, considered the regulation mechanisms of microcirculation, the level of oxygen saturation of hemoglobin both in the circulation system and mixed blood, the index of oxygen utilization in tissues and the value of fluorescent use of oxygen. We received the information about the changes in the frequency of occurrence of different microcirculation types associated with the age and region of residence. In the case of higher radiation levels we marked a significant increase of individuals with the "extreme" microcirculation type (hypoemic and hyperemic) against the background of the decreased mesoemic type. A special feature of the metabolism process in children, teenagers, and youths is a decrease of the microcirculation density with an increase of the myogenic tone of metaarterioles and precapillary sphincters. The tone of arterioles grows with age. As a result of the limited blood volume, oxygen. is pulled compensatory from blood in larger amounts; it is shown from a significant decrease of the level of oxygen saturation in mixed blood. The strongest differences are shown for the hypoemic and hyperemic microcirculation type. Dwelling on the areas with radio-ecological pressure is accompanied by an increase in the fluorescent index of oxygen use. The level of the total oxygen use in these individuals is higher than in those living in radiation favorable areas.

Effect of incubating egg exposure to magnetic field on the biophysical blood properties of newly-hatched chicks.

Due to widespread of human exposure to electromagnetic fields, there has been increasing public concern about the potential health risks from low-frequency electromagnetic fields; ELF-EMF. The magnetic fields (MFs) affects functions of the living organisms, such as DNA synthesis and ion transportation through the cell membranes. In the present work, the effects of short-term exposure to magnetic fields (MFs) prior to incubation were investigated on the biophysical blood properties of chicks hatched from layer-type breeder eggs. The eggs were exposed to a MF of 0.75 mT at 50 Hz for 20, 40 and 60 min before incubation. This study was performed by measuring the dielectric relaxation of hemoglobin (Hb) molecules and the membrane solubility of red blood cells (RBCs) using the non-ionic detergent octylglucoside. Exposure of the eggs to a MF increased the conductivity of the Hb molecules. The pronounced increase in the conductivity of the exposed eggs might be attributed to an increase in the surface charge of the Hb macromolecules, resulted from the formation of highly active molecular species. This speculation can be supported by the increase in the relaxation time of the exposed groups. The solubilization process of the RBC membrane indicates a loss in the mobility of RBCs in the blood of hatching chicks.

Selective X-ray-induced NO photodissociation in haemoglobin crystals: evidence from a Raman-assisted crystallographic study.

Despite their high physiological relevance, haemoglobin crystal structures with NO bound to haem constitute less than 1% of the total ligated haemoglobins (Hbs) deposited in the Protein Data Bank. The major difficulty in obtaining NO-ligated Hbs is most likely to be related to the oxidative denitrosylation caused by the high reactivity of the nitrosylated species with O(2). Here, using Raman-assisted X-ray crystallography, it is shown that under X-ray exposure (at four different radiation doses) crystals of nitrosylated haemoglobin from Trematomus bernacchii undergo a transition, mainly in the ß chains, that generates a pentacoordinate species owing to photodissociation of the Fe-NO bond. These data provide a physical explanation for the low number of nitrosylated Hb structures available in the literature.

The effect of γ-radiation on the hemoglobin of stored red blood cells: the involvement of oxidative stress in hemoglobin conformation.

The aim of the present work was to evaluate the redox and oligomeric effects associated with the human hemoglobin of stored red blood cells that had been previously submitted to gamma radiation. Whole blood was collected from healthy donors and irradiated with 25 Gy of γ-radiation within 24 h of collection. At days 3, 5, 7, 9, 11, 14, and 28 postirradiation, fractions were removed and centrifuged, and the levels of methehemoglobin and oxyhemoglobin were measured. Hb was isolated to measure the denaturation and UV-vis spectra. The results from electrophoresis demonstrated that there was no fragmentation or cross-linking of the hemoglobin. However, ferrous center oxidation was identified as a very significant process. This mechanism is likely through an autoxidation process of the ferrous heme center, which has a maximal intensity between 5 and 7 days of storage. Interestingly, a subsequent reduction of the oxidized heme species was observed, and after 9 days of storage, the difference between the ferric species present in the control and irradiated samples was not representative. This interesting fact suggests a type of "protective action" by the blood to control the oxidative stress generated by the gamma irradiation. The UV-vis measurements demonstrated that the oxidized species was predominantly formed by hemichrome species (bis-histidine ferric heme species), which are usually associated with Heinz bodies. After 28 days of storage, evidence from the UV-vis measurements indicated that the oxidation of the irradiated sample was much higher than that observed in the control sample. These results demonstrate that despite the minimal polypeptide changes observed in the hemoglobin of stored red blood cells after gamma irradiation, the oxidation of the heme metallic center is not irrelevant and must be controlled to improve the hematological clinical procedures associated with the storage of red blood cells.

The influence of pulsed electric field on hematological parameters in rat.

The aim of the present study is to investigate whether or not pulsed electric field (PEF) affects some hematological parameters in rats. Sixteen healthy male Wistar rats weighting 150-200 g were used and were randomly divided into two groups. Exposure group (n = 8) was exposed to a PEF (10 kV m⁻¹ for 1 h d⁻¹) for 10 consecutive days. The control group rats (n = 8) were not exposed to PEF. The following hematological parameters were measured in both the groups: white blood cells (WBCs), red blood cells (RBCs), hemoglobin (Hb), hematocrit (Ht) and platelets (PLTs). Some of the hematological parameters under investigation were similar in both the groups. Exposure group, exposed for 1 h d⁻¹ during 10 consecutive days, induced a significant increase in the rates of WBC (p < 0.05), RBC (p < 0.05), Hb (p < 0.05), Ht (p < 0.05) and PLTs (p < 0.05) in blood when compared with control. These results suggest that PEFs affect the hematological parameters in rat. Results of the parameters are statistically significant.

[Role of optical properties of the venous wall for endovenous laser obliteration].

Presented herein are the results of studying the optical density of water, blood, and venous-wall tissue for various-wavelength laser radiation, with determining the peaks of absorption of radiation by the above-mentioned media. The absorption peaks in water and blood correspond to wavelengths of 1,450 and 1,935 nm, respectively. Peaks of absorption in the venous-wall tissue are within the intervals equaling 650-950 nm, 1,445-1,455 nm, and more than 1,900 nm. Also determined was the optical density of the veins for the most frequently used in clinical practice wavelengths, i. e. 1,030 and 1,470 nm, with the calculation of the portion of the absorbed energy depending on thickness of the layer of the absorbing substance. Based on the obtained findings, a conclusion was drawn on better utilization of the energy of one-and-a-half-micron range laser radiation and on its preferable use for endovenous laser obliteration (EVLO).

Vertebrate ancient opsin photopigment spectra and the avian photoperiodic response.

In mammals, photoreception is restricted to cones, rods and a subset of retinal ganglion cells. By contrast, non-mammalian vertebrates possess many extraocular photoreceptors but in many cases the role of these photoreceptors and their underlying photopigments is unknown. In birds, deep brain photoreceptors have been shown to sense photic changes in daylength (photoperiod) and mediate seasonal reproduction. Nonetheless, the specific identity of the opsin photopigment 'sensor' involved has remained elusive. Previously, we showed that vertebrate ancient (VA) opsin is expressed in avian hypothalamic neurons and forms a photosensitive molecule. However, a direct functional link between VA opsin and the regulation of seasonal biology was absent. Here, we report the in vivo and in vitro absorption spectra (λ(max) = ~490 nm) for chicken VA photopigments. Furthermore, the spectral sensitivity of these photopigments match the peak absorbance of the avian photoperiodic response (λ(max) = 492 nm) and permits maximum photon capture within the restricted light environment of the hypothalamus. Such a correspondence argues strongly that VA opsin plays a key role in regulating seasonal reproduction in birds.

Irradiated stem cells and ageing of the haematopoietic system.

In the work presented here, changes in haematopoiesis of mice (B6129SF2/J) were studied 1 year after their whole-body exposure to a dose of 7 Gy (72% of mice survived). The irradiated mice were compared with non-irradiated younger (4 months of age) and older (16 months of age) mice. There was a significant increase in the relative abundance of primitive stem cells with long-term capability of the haematopoiesis recovery lin(-)/Sca-1(+)/CD117(+)/CD34(-) in the bone marrow of mice aged 16 months (irradiated and non-irradiated) compared with those aged 4 months. In terms of the ability to respond to further whole-body irradiation at a dose of 1 Gy, the presence of γH2A.X foci was studied in lin(-) bone marrow cells. There was a considerable number of persisting foci in lin(-) stem cells isolated from the bone marrow of the older irradiated mice. In the blood count from the peripheral blood of the older mice (both non-irradiated and irradiated at 7 Gy), there was a significant increase in granulocytes. In the group exposed to 7 Gy, the numbers of thrombocytes significantly increased, and on the contrary, the numbers of erythrocytes, the amount of haemoglobin, and haematocrit significantly decreased.

Short laser pulse-induced irreversible photothermal effects in red blood cells.

BACKGROUND AND OBJECTIVES: Photothermal (PT) responses of individual red blood cells (RBC) to short laser pulses may depend upon PT interactions at microscale. STUDY DESIGN/MATERIALS AND METHODS: A sequence of identical short laser pulses (0.5 and 10 nanoseconds, 532 nm) was applied to individual RBCs, and their PT properties were analyzed at microscale in real time after each single pulse. RESULTS: PT interactions in RBC were found to be localized to sub-micrometer zones associated with Hb that may be responsible for overheating and evaporation at higher optical energies. At sub-ablative energies, a single short laser pulse induced irreversible changes in the optical properties of RBC that stimulated the transition from a heating-cooling response to ablative evaporation in individual erythrocytes during their exposure to subsequent, but identical pulses. CONCLUSION: The PT response of RBCs to short laser pulses of specific energy includes localized irreversible modifications of cell structure, resulting in three different effects: thermal non-ablative response, ablative evaporation, and residual thermal response.

[Studies of physical and chemical properties of the vacuum UV-irradiated molecules of human hemoglobin and its components (heme and globin)].

The purpose of the present work is to study the vacuum ultraviolet radiation action on the optical and chromatographic characteristics of human hemoglobin molecules and their components - haem and globin. Using the methods of spectrophotometry and thin layer chromatography (TLC), we have investigated into the structural changes of molecules of human hemoglobin, haem and globin, induced by the influence of vacuum UV light (gamma = 118-134 nm, dose - 1.2 kJ/m2). It has been shown that vacuum ultraviolet radiation induces an infringement of the higher types of the spatial organization ofglobin molecules, thus leading to the changes in the structural state of the albuminous globule.

Effect of X-ray free-electron laser-induced shockwaves on haemoglobin microcrystals delivered in a liquid jet.

X-ray free-electron lasers (XFELs) enable obtaining novel insights in structural biology. The recently available MHz repetition rate XFELs allow full data sets to be collected in shorter time and can also decrease sample consumption. However, the microsecond spacing of MHz XFEL pulses raises new challenges, including possible sample damage induced by shock waves that are launched by preceding pulses in the sample-carrying jet. We explored this matter with an X-ray-pump/X-ray-probe experiment employing haemoglobin microcrystals transported via a liquid jet into the XFEL beam. Diffraction data were collected using a shock-wave-free single-pulse scheme as well as the dual-pulse pump-probe scheme. The latter, relative to the former, reveals significant degradation of crystal hit rate, diffraction resolution and data quality. Crystal structures extracted from the two data sets also differ. Since our pump-probe attributes were chosen to emulate EuXFEL operation at its 4.5 MHz maximum pulse rate, this prompts concern about such data collection.

Apparent desaturation on pulse oximetry because of hemoglobinopathy.

Hemoglobinopathies are an uncommon cause of cyanosis and low oxygen saturation on pulse oximetry. However, when they do occur, they can present a complex clinical scenario for the emergency physician. We report the index case of a previously undescribed hemoglobinopathy that presented to the pediatric emergency department. The evaluation and management of the cyanotic/hypoxic child and review of hemoglobinopathies are presented here.

Protective properties of Myrtus communis extract against oxidative effects of extremely low-frequency magnetic fields on rat plasma and hemoglobin.

PURPOSE: This study investigates the protective properties of Myrtus communis extract against the oxidative effects of extremely low-frequency magnetic fields (ELFMF). Also, this study is aimed to analyze the conformational changes of hemoglobin, oxidative damages to plasma proteins and antioxidant power of plasma following exposure to ELFMF. MATERIALS AND METHODS: Adult male rats were divided into 3 groups: (1) control, (2) ELFMF exposure, and (3) ELFMF exposure after M. communis extract administration. The magnetic field (0.7 mT, 50 Hz) was produced by a Helmholtz coil for one month, 2 hours a day. The M. communis extract was injected intraperitoneally at a dose of 0.5 mg/kg before exposure to ELFMF. The oxidative effects of ELFMF were studied by evaluating the hemoglobin, methemoglobin (metHb) and hemichrome levels, absorption spectrum of hemoglobin (200-700 nm), oxidative damage to plasma proteins by measuring protein carbonyl (PCO) levels and plasma antioxidant power according to the ferric reducing ability of plasma (FRAP). The mean and standard errors of the mean were determined for each group. One-way ANOVA analysis was used to compare the means of groups. The significance level was considered to be p < .05. Moreover, artificial neural network (ANN) analysis was used to identify the predictive parameters for estimating the oxyhemoglobin (oxyHb) concentration. RESULTS: Exposure to ELFMF decreased the FRAP which was in concomitant with a significant increase in plasma PCO, metHb and hemichrome concentrations (p < .001). Oxidative modifications of Hb were shown by reduction in optical density at 340 nm (globin-heme interaction) and 420 nm (heme-heme interaction). Administration of M. communis extract increased FRAP values and decreased plasma POC, metHb, and hemichrome concentrations. Also, a significant increase in Hb absorbance at 340, 420, 542, and 577 nm showed the protective properties of M. communis extract against ELFMF-induced oxidative stress in erythrocytes. ANN analysis showed that optical absorption of hemoglobin at 520, 577, 542, and 630 nm and concentration of metHb and hemichrome were the most important parameters in predicting the oxyHb concentration. CONCLUSIONS: Myrtus communis extract enhances the ability of erythrocytes and plasma to deal with oxidative conditions during exposure to ELFMF. Also, ANN analysis can predict the most important parameters in relation to Hb structure during oxidative stress.

State-of-the-Art Preclinical Photoacoustic Imaging in Oncology: Recent Advances in Cancer Theranostics.

The optical imaging plays an increasing role in preclinical studies, particularly in cancer biology. The combined ultrasound and optical imaging, named photoacoustic imaging (PAI), is an emerging hybrid technique for real-time molecular imaging in preclinical research and recently expanding into clinical setting. PAI can be performed using endogenous contrast, particularly from oxygenated and deoxygenated hemoglobin and melanin, or exogenous contrast agents, sometimes targeted for specific biomarkers, providing comprehensive morphofunctional and molecular information on tumor microenvironment. Overall, PAI has revealed notable opportunities to improve knowledge on tumor pathophysiology and on the biological mechanisms underlying therapy. The aim of this review is to introduce the principles of PAI and to provide a brief overview of current PAI applications in preclinical research, highlighting also on recent advances in clinical translation for cancer diagnosis, staging, and therapy.

Conformational dynamics associated with photodissociation of CO from dehaloperoxidase studied using photoacoustic calorimetry.

Herein, we present photoacoustic calorimetry and transient absorption studies of the dynamics and energetics associated with dissociation of a ligand from Fe(2+) dehaloperoxidase (DHP) from Amphitrite ornata. Our data show that CO photodissociation is associated with an endothermic (DeltaH = 8 +/- 3 kcal mol(-1)) volume expansion (DeltaV = 9.4 +/- 0.6 mL mol(-1)) that occurs within 50 ns upon photodissociation. No additional thermodynamics were detected on slower time scales (up to 10 micros), suggesting that the dissociated ligand rapidly escapes from the heme-binding pocket into the surrounding solvent. Similar volume and enthalpy changes were observed for CO photodissociation in the presence of the substrate, 2,4-dichlorophenol or 4-bromophenol, indicating that either the substrate does not bind in the protein distal cavity at ambient temperature or its presence does not impact the thermodynamic profile associated with ligand dissociation. We attribute a fast ligand exchange between the protein active site and the surrounding solvent to the high flexibility of the distal histidine residue, His55, that provides a direct pathway between the heme-binding pocket and the protein exterior. The dynamics and energetics of conformational changes observed for dissociation of a ligand from DHP differ significantly from those measured previously for photodissociation of CO from the structural homologue myoglobin, suggesting that structural dynamics in DHP are fine-tuned to enhance the peroxidase function of this protein.

Inactivation of chosen dehydrogenases by the products of water radiolysis and secondary albumin and haemoglobin radicals.

PURPOSE: Inactivation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), alcohol dehydrogenase (ADH) and lactate dehydrogenase (LDH) by products of water radiolysis and by secondary radicals localized on haemoglobin (Hb) and human albumin (HSA) was studied. MATERIALS AND METHODS: Aqueous solutions of ADH, GAPDH and LDH were irradiated under air and under nitrous oxide (N2O) in the absence and in the presence of Hb or HSA. In order to determine the effectiveness of inactivation of the enzymes by radicals localized on Hb and HSA, the inactivation efficiency determined experimentally was compared with that calculated under assumption that only hydroxyl radicals are responsible for the enzyme inactivation. RESULTS: In the absence of other proteins, under air, GAPDH showed the highest radiation sensitivity, followed by ADH and LDH. The sequence was reverse under anaerobic atmosphere. Oxygen increased considerably the inactivation of GAPDH and ADH. Secondary albumin and haemoglobin radicals brought about considerable inactivation of GAPGH and ADH. Albumin radicals (HSA) generated under N2O inactivated GAPDH and ADH more effectively than haemoglobin radicals (Hb). Under air, however, inactivation of GAPDH and ADH by haemoglobin peroxyl radicals was higher than by albumin peroxyl radicals. LDH was resistant to inactivation by haemoglobin and albumin radicals, and peroxides of these proteins. CONCLUSIONS: In the light of these results and literature data, the observed differences in the effectiveness of inactivation of the dehydrogenases studied by secondary protein radicals depend on the amino acid residues present at the active site and in its close neighborhood and on the number of amino acid residues available on the protein surface.

Amelioration of radiation-induced hematological and biochemical alterations by Alstonia scholaris (a medicinal plant) extract.

The radioprotective efficacy of a hydro-alcoholic extracted material from the bark of Alstonia scholaris (ASE) was studied in mice against radiation-induced hematological and biochemical alterations. Swiss albino mice were administered ASE (100 mg/kg body weight/d for 5 consecutive day) orally prior to whole-body gamma irradiation (7.5 Gy). Radiation exposure resulted in a significant decline (P<.001) in erythrocytes and hemoglobin until the third day, following a gradual recovery (ie, day 7), but these values did not reach normal values during the remainder of the animals' life span. Hematocrit percentage declined significantly (P<.001) until day 15. In contrast, ASE-pretreated irradiated animals had significantly higher erythrocyte, hematocrit, and hemoglobin values than the irradiated controls. Furthermore, a significant elevation in lipid peroxidation level over normal was recorded in gamma-irradiated mice, whereas this increase was considerably lower in ASE-pretreated animals. Pretreatment with ASE caused a significant increase in glutathione levels in serum as well as in liver in comparison to irradiated animals. This study showed that ASE protects against radiation-induced hematological and biochemical alterations in Swiss albino mice.