Functionalization of the Implant Surface Made of NiTi Shape Memory Alloy.

To functionalize and improve the biocompatibility of the surface of a medical implant made of NiTi shape memory alloy and used in practice, a clamp, multifunctional layers composed of amorphous TiO2 interlayer, and a hydroxyapatite coating were produced. Electrophoresis, as an efficient method of surface modification, resulted in the formation of a uniform coating under a voltage of 60 V and deposition time of 30 s over the entire volume of the implant. The applied heat treatment (800 °C/2 h) let toa dense, crack-free, well-adhered HAp coating with a thickness of ca. 1.5 µm. and a high crack resistance to deformation associated with the induction of the shape memory effect in the in the deformation range similar to the real implant work after implantation. Moreover, the obtained coating featured a hydrophilic (CA = 59.4 ± 0.3°) and high biocompatibility.

Determination of Internal Temperature by Measuring the Temperature of the Body Surface Due to Environmental Physical Factors-First Study of Fever Screening in the COVID Pandemic.

The SARS-CoV-2 virus pandemic has shown that the use of a contact thermometer to verify the elevated body temperature of a suspected person carries a risk of spreading disease. The perfect solution seems to be the use of thermal imaging as a diagnostic method in fever evaluation. The aim of the research is to develop an algorithm for thermovision measurements in fever screening standards in the context of the impact of various weather conditions on the temperature of people entering the public institution. Each examined person had two thermal images of the face-AP and lateral projection. Using a T1020 FLIR thermal camera with a resolution of 1024 × 768 pixels; the mean temperature was measured from the area of the forehead, the maximum forehead, the corners of the eyes, the inside of the mouth and the external auditory canal temperature. On the other hand, using classic contact thermometers, the temperature in the armpit and ear was measured. The obtained preliminary results showed very strong and positive correlations between the temperature in the ear measured with an ear thermometer and the maximum, minimum and average forehead temperature. These correlations oscillate at approximately r = 0.6, but the highest value of Spearman coefficient was obtained for the mean temperature of the forehead. Moreover, high correlations were also obtained between the temperature in the ear, measured with an ear thermometer, and the maximum temperature in the corners of the eyes and in the ear, measured with a thermal imaging camera. These values were, respectively, r = 0.54, r = 0.65. In summarizing, remote body temperature measurement taken with a thermal camera can be useful in the assessment of the body's core temperature.

Is Thermal Imaging a Helpful Tool in Diagnosis of Asymptomatic Odontogenic Infection Foci-A Pilot Study.

Since the identification of periapical lesions typically requires invasive testing that may adversely affect individuals suffering from concomitant disease, the diagnosis of apical periodontitis remains a challenge. This study aimed to determine the effectiveness of infrared thermal imaging for the detection of asymptomatic odontogenic inflammatory response in patients with a high risk of systemic infections. The examinations were performed using the FLIR T1020 thermal camera. The acquired images were analyzed with a ThermaCAM TM Researcher Pro 2.8 SR-3. Statistical analyses were conducted using the Statistica 10 software. The Mann-Whitney U test was used for data that were not normally distributed or did not meet the assumption of homogeneity of variance, while normally distributed data were analyzed with the t-test. The mean temperature difference between the periapical regions of the suspect and contralateral teeth was found to be greatest at 30 s of mouth opening. This is a preliminary study conducted to evaluate the potential of infrared thermal imaging as a diagnostic tool for the identification and elimination of odontogenic infection foci. Thermography seems to facilitate the quantitative assessment of inflammation by displaying temperature differences between the affected and unaffected regions.

Thermovision as a Tool for Athletes to Verify the Symmetry of Work of Individual Muscle Segments.

In the presented research, we characterised the temperature profiles and the degree of preparation for exercise of individual muscle groups of athletes We hypothesise that by means of thermal imaging studies, the effectiveness of the warm-up can be monitored to determine whether the effort of individual muscles is equal and symmetrical, which can help to avoid a potential injury. In the study, thermographic imaging was performed on a group of athletes exercising on a rowing ergometer involving almost 80% of the muscle parts of the human body for intense and symmetrical exercise. Thermovision studies have confirmed, based on the increased temperature of the muscle areas, that the rowing ergometer involves many muscle groups in training. Moreover, based on the shape of the temperature function obtained from individual body regions of interest, it was shown that conventional exercise on a rowing ergometer causes almost symmetrical work of the right and left sides of the body. Obtained temperature changes in most of the studied muscle areas showed minimum temperature reached the beginning of training-mostly phases 1 and 2. During the subsequent phases, the temperature increase was monitored, stopping at resting temperature. Significantly, temperature variations did not exceed 0.5 °C in all post-training phases. Statistical analyses did not show any significant differences in the symmetry of right and left muscle areas corresponding to the muscle location temperature. Thermal imaging may be an innovative wholly non-invasive and safe method, because checking induces adaptation processes, which may become indicators of an athlete's efficiency. The imaging can be continuously repeated, and automatic comparison of average temperature or temperature difference may provide some clues that protect athletes from overtraining or serious injuries.

Physical parameters in thermal imaging of basal cell cancer patients treated with high-dose-rate brachytherapy - first study.

Background: The basal cell carcinoma (BCC) is often treated by surgery or radiotherapy using ionizing radiation. While there is an established diagnostic path before treatment and also for the follow-up there are no good noninvasive methods objectifying irradiated area evolution during treatment. The main goal of preliminary studies was to try to answer if there are any useful information that can be derived from temperature effects of high-dose-rate (HDR) brachytherapy in treatment of BCC. Moreover, the temperature gradient was introduced as a physical parameter characterizing the thermal map of the lesion, its surroundings and reference area, which provided information about cancer tissue thermal reaction to brachytherapy. Materials and methods: Thirty-three patients suffering from BCC were monitored with thermovision during the brachytherapy treatment. All lesions were diagnosed as superficial and were confirmed with histopathology examination. Results: Results of the study showed two groups of patients characterized with two thermal maps and temperature gradient describing the lesion and surrounding area of BCC. The first group was characterized by higher temperature of the lesion than the surrounding tissue temperature (mean dT = 0,41°) whereas the other one, with lower lesion temperature (mean dT = -0.42°). It seems that the temperature changes observed in designated areas before and after therapy may provide physicians with additional information which could be useful in planning the treatment process, especially when considering temperature gradient changes during therapy. Conclusions: Although the data obtained indicate the possibilities of temperature distribution in pre-irradiation cases, further research is required for estimation of clinical effects of treatment.

Usefulness in Developing an Optimal Training Program and Distinguishing between Performance Levels of the Athlete's Body by Using of Thermal Imaging.

The goal of the training is to enable the body to perform prolonged physical effort without reducing its effectiveness while maintaining the body's homeostasis. Homeostasis is the ability of the system to maintain, in dynamic balance, the stability of the internal environment. Equally as important as monitoring the body's thermoregulation phenomena during exercise seems to be the evaluation of these mechanisms after physical effort, when the athlete's body returns to physiological homeostasis. Restoring homeostasis is an important factor in body regeneration and has a significant impact on preventing overtraining. In this work we present a training protocol using a rowing ergometer, which was planned to be carried out in a short time and which involves working the majority of the athlete's muscles, allowing a full assessment of the body's thermal parameters after stopping exercise and during the body's return to thermal equilibrium and homeostasis. The significant differences between normalized mean body surface temperature obtained for the cyclist before the training period and strength group as well as before and 10 min after training were obtained. Such observation seems to bring indirectly some information about the sportsperson's efficiency due to differences in body temperature in the first 10 min of training when sweat does not play a main role in surface temperature. Nearly 1 °C drop of mean body temperature has been measured due to the period of training. It is concluded that thermovision not only allows you to monitor changes in body temperature due to sports activity, but also allows you to determine which of the athletes has a high level of body efficiency. The average maximum body temperature of such an athlete is higher (32.5 °C) than that of an athlete who has not trained regularly (30.9 °C) and whose body probably requires further training.

Monitoring PDT effects in basal cell carcinoma treatment using thermal imaging.

BACKGROUND: One of the most frequent type of malignant skin lesion (almost 95 percent of all skin tumours) is basal cell carcinoma (BCC). It is often treated by radiotherapy using ionizing radiation as well by photodynamic therapy (PDT) which is a selective method directed only on cancer cells and well tolerated by patients. MATERIALS AND METHODS: Eight male patients of the Department and Clinic of Internal Diseases, Angiology and Physical Medicine in Bytom, Medical University of Silesia, in Katowice, Poland suffering from basal cell carcinoma were monitored by thermovision during the photodynamic therapy. All lesions were diagnosed as superficial were confirmed by histopathological examination. RESULTS: The dynamics of changes observed in the isotherm area during the therapy can provide physicians with additional information. The significant increase of observed isotherm area in comparison to the lesion area diagnosed by a physician was confirmed, which may be connected with the increased metabolism processes occurring in the tissue surrounded the lesion. CONCLUSION: The obtained results based on the temperature gradient changes in the lesion vicinity area may bring some new information describing the range of biochemical and physiological processes occurring during photodynamic therapy.

Photodynamic performance of amphiphilic chlorin e6 derivatives with appropriate properties: A comparison between different-type liposomes as delivery systems.

BACKGROUND: Many aspects are currently being investigated, with the aim of improving the application of PDT in the clinic by rendering it more effective. One of the current trends focuses on the use of nanocarriers. The aim of this study is to describe novel photosensitizers among polyol amide chlorin e6 derivatives for photodynamic therapy (PDT) using liposomes. METHODS: In addition to their intracellular localization and antiproliferative activity against HCT116 cells, appropriate photophysical features have been determined (especially high 1O2 quantum yield production). RESULTS AND CONCLUSIONS: Fluorescent microscopy demonstrated that the compounds entered the endoplasmic reticulum (ER), lysosomes, mitochondria and partially the cytoplasm. All of the chlorins showed no dark cytotoxicity; however, high phototoxicity was observed. Using optical and electron microscopy, we investigated the impact of chlorin-based PDT upon cell damage leading to cell death. Chl ara 3 was identified as the most promising compound among polyol amide chlorin e6 derivatives and improved phototoxicity was observed as compared with a clinically approved temoporfin. Our results indicate that newly-synthesized chlorins seem to be promising candidates for PDT application, and two of them (chl ara 3 and chl mme 2) may create promising new drugs, both in the form of a free compound and as a liposomal formulation.

Platinum(II) coordination compounds with 4'-pyridyl functionalized 2,2':6',2″-terpyridines as an alternative to enhanced chemotherapy efficacy and reduced side-effects.

Two platinum(II) coordination compounds, [PtCl(4'-R1-terpy)](SO3CF3) (1) and [PtCl(4'-R2-terpy)](SO3CF3) (2), with 4'-(2-pyridyl)-2,2':6',2″-terpyridine (4'-R1-terpy) or 4'-(3-pyridyl)-2,2':6',2″-terpyridine (4'-R2-terpy) were synthesized and the impact of the pendant pyridyl ring on the structure and cytotoxic activity of Pt(II)-terpyridine complexes was explored. The single-crystal X-ray diffraction analysis confirmed square planar coordination of the cations [PtCl(4'-Rn-terpy)]+. The mode of binding of 1 and 2 to calf thymus DNA was examined by UV-Vis absorption titration, ethidium displacement assay and reaction with 9-ethylguanine, and the mixed covalent-intercalative mode was demonstrated. The cytotoxicity of the Pt(II) complexes against six cancer cell lines and three normal ones was determined using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay and compared to cisplatin. The IC50 values for the compound 2 towards the cancer cell lines are in the low micromolar range. Most remarkably, 2 was over 4 times more effective than 1 and cisplatin against non-small lung adenocarcinoma (A549), and its selectivity index was ~60-80 times higher than that for 1 and cisplatin. The mechanisms underlying the loss of viability under treatment of 2 was further investigated including F-actin staining, mitotic index analysis, cytometric cell cycle analysis, Fluorescein isothiocyanate (FITC) -conjugated Annexin V antibody and propidium iodide (PI) staining, measurements of reactive oxygen species (ROS) in cells, analysis of changes in the mitochondrial mass and potential and quantitative real time polymerase chain reaction (qRT-PCR) genes analysis. The compound 2 was found to have a pro-oxidative effect by strong stimulation of cells for the production of reactive oxygen species and cytostatic effect through cell cycle arrest.

Iron chelators in photodynamic therapy revisited: synergistic effect by novel highly active thiosemicarbazones.

In photodynamic therapy (PDT), a noninvasive anticancer treatment, visible light, is used as a magic bullet selectively destroying cancer cells by a photosensitizer that is nontoxic in the dark. Protoporphyrin IX (PpIX) is a natural photosensitizer synthesized in the cell, which is also a chelating agent that if bonded to Fe(2+) forms heme, a central component of hemoglobin. Therefore, xenobiotic iron chelators can disturb iron homeostasis, increasing the accumulation of PpIX, obstructing the last step of heme biosynthesis, and enhancing PDT efficiency. However, the attempts to use this promising idea have not proved to be hugely successful. Herein, we revisited this issue by analyzing the application of iron chelators highly toxic in the dark, which should have higher Fe(2+) affinity than the nontoxic chelators used so far. We have designed and prepared thiosemicarbazones (TSC) with the highest dark cellular cytotoxicity among TSCs ever reported. We demonstrate that compound 2 exerts powerful PDT enhancement when used in combination with 5-aminolevulinic acid (ALA), a precursor of PpIX.

DFT/TD-DFT study of solvent effect as well the substituents influence on the different features of TPP derivatives for PDT application.

Spectral characteristics study of meso-tetraphenylporphyrin derivatives (TPP1 and TPP2) used as photosensitizers for utilization in photodynamic therapy (PDT) has been performed by density functional theory (DFT) and time dependent DFT (TD-DFT) calculations at B3LYP/6-31 G(d) level of theory using PCM solvation model. The geometrical parameters of porphyrins have been studied for ground and excited-state geometry to deduce the influence of various substituents as well as solvent effect on the deformation of porphyrin ring. Two theoretical approaches - linear response (LR) and external iteration (EI) - have been performed to replicate absorption and fluorescence emission spectra. Experimental and theoretical investigations have shown that EI method reproduces the absorption energies very well for both singlet-singlet and triplet-triplet transitions, whereas the LR approach is more coherent with experimental fluorescence emission spectra. Spectral features and HOMO-LUMO band gap analysis have shown that TPP1 can be more useful in PDT. Calculations have revealed that two the highest occupied and two the lowest unoccupied molecular orbitals are responsible for the Q-band absorption and are located mainly on the porphyrin ring. In order to verify the substituent effect on the activity of tested compounds in their ground and excited states, the molecular electrostatic potential surfaces have been analyzed.

Synthesis and characterization of quinoline-based thiosemicarbazones and correlation of cellular iron-binding efficacy to anti-tumor efficacy.

Iron chelators have emerged as a potential anti-cancer treatment strategy. In this study, a series of novel thiosemicarbazone iron chelators containing a quinoline scaffold were synthesized and characterized. A number of analogs show markedly greater anti-cancer activity than the 'gold-standard' iron chelator, desferrioxamine. The anti-proliferative activity and iron chelation efficacy of several of these ligands (especially compound 1b), indicates that further investigation of this class of thiosemicarbazones is worthwhile.

Synthesis and in vitro antiproliferative activity of 5-alkyl-12(H)-quino[3,4-b] [1,4]benzothiazinium salts.

A novel method of synthesizing 1,4-thiazine ring has led to the series of 5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazinium salts. The derivatives containing a butyl or decyl substituents on the quinoline nitrogen atom were obtained by alkylation of 12(H)-quino[3,4-b][1,4]benzothiazine with alkyl bromides. Antiproliferative activity in vitro of the compounds (3) was assessed using two cancer cell lines (Hct116 and LLC) and doxorubicin as a reference. Most of the studied phenothiazine derivatives showed activity against both cell lines investigated (2.2-19.6 µg/mL concentration range). A structure-activity relationship was established. Only the compounds with substituents in the 11-position of the quinobenzothiazine ring did not exhibit activity against either cell line.

Investigating the anti-proliferative activity of styrylazanaphthalenes and azanaphthalenediones.

A group of styrylazanaphthalenes and azanaphthalenediones were synthesized and tested for their anti-proliferative activity. Most of the compounds were obtained with the use of microwave-assisted synthesis. The lipophilicity of the compounds was measured by RP-HPLC and their anti-proliferative activity was assayed against the human SK-N-MC neuroepithelioma and HCT116 human colon carcinoma cell lines. Active compounds were also tested in clonogenity and comet assays. Several quinazolinone and styrylquinazoline analogues were found to have markedly greater anti-proliferative activity than desferoxamine and cis-platin.

Spectroscopic and biological studies of a novel synthetic chlorin derivative with prospects for use in PDT.

Photosensitizers with desirable combinations of chemical, photophysical and biological properties are essential for improving the efficacy of photodynamic therapy (PDT) against various cancers. Chlorins seem to be promising candidates for photodynamic therapy (PDT) owing to their photophysical properties. This paper reports spectroscopic and biological properties of a novel synthetic chlorin derivative. Cytotoxicity, phototoxicity as well as subcellular localization of the novel derivative was studied using Lewis lung carcinoma cultured cells (LLC). In the examined concentration range no significant cytotoxic effects were found but high phototoxicity was observed. Confocal laser scanning microscopy demonstrated that the compound, upon entering cells, was localized in the perinuclear cytoplasm of LLC cells. Using fluorescent microscopy we investigated the impact of PDT based on the novel compound upon cytoskeleton and DNA structure of LLC cells. Our results indicate that liposomes are effective in transferring the chlorin photosensitizer into the studied cells, leading to their high photosensitization, whereas the non-carrier delivery mode (i.e., DMSO) is rather useless for such purposes.

[Dose rate-dependent cellular and molecular effects of ionizing radiation]. / Wplyw mocy dawki na komórkowe, biochemiczne i molekularne efekty promieniowania jonizujacego.

The aim of radiation therapy is to kill tumor cells while minimizing damage to normal cells. The ultimate effect of radiation can be apoptotic or necrotic cell death as well as cytogenetic damage resulting in genetic instability and/or cell death. The destructive effects of radiation arise from direct and indirect ionization events leading to peroxidation of macromolecules, especially those present in lipid-rich membrane structures as well as chromatin lipids. Lipid peroxidative end-products may damage DNA and proteins. A characteristic feature of radiation-induced peroxidation is an inverse dose-rate effect (IDRE), defined as an increase in the degree of oxidation(at constant absorbed dose) accompanying a lower dose rate. On the other hand, a low dose rate can lead to the accumulation of cells in G2, the radiosensitive phase of the cell cycle since cell cycle control points are not sensitive to low dose rates. Radiation dose rate may potentially be the main factor improving radiotherapy efficacy as well as affecting the intensity of normal tissue and whole-body side effects. A better understanding of dose rate-dependent biological effects may lead to improved therapeutic intervention and limit normal tissue reaction. The study reviews basic biological effects that depend on the dose rate of ionizing radiation.

Spectroscopic properties and photodynamic effects of new lipophilic porphyrin derivatives: efficacy, localisation and cell death pathways.

Photodynamic therapy (PDT) and photodynamic diagnostics (PDD) of cancer are based on the use of non-toxic dyes (photosensitisers) in combination with harmless visible light. This paper reports physicochemical properties, cell uptake, localisation as well as photodynamic efficiency of two novel lipophilic porphyrin derivatives, suitable for use as PDT sensitisers. Both compounds are characterised by high quantum yield of singlet oxygen generation which was measured by time-resolved phosphorescence. Photodynamic in vitro studies were conducted on three cancer cell lines. Results of cell survival tests showed negligible dark cytotoxicity but high phototoxicity. The results also indicate that cell death is dependent on energy dose and time following light exposure. Using confocal laser scanning microscopy both compounds were found to localise in the cytoplasm around the nucleus of the tumour cells. The mode of cell death was evaluated based on the morphological changes after differential staining. In summary, good photostability, high quantum yield of singlet oxygen and biological effectiveness indicate that the examined lipophilic porphyrin derivatives offer quite interesting prospects of photodynamic therapy application.

Multiple bystander effect of irradiated megacolonies of melanoma cells on non-irradiated neighbours.

The multicellular megacolonies of human melanoma Me45 line growing on one part of the bottom of culture flasks were irradiated with 5 Gy (60Co), whereas megacolonies growing on the second part of the bottom were shielded. The bystander effect of radiation-traversed cells on non-traversed cells was studied during postradiation co-cultivation. Activity of superoxide dismutase (Mn and CuZn subunits), glutathione peroxidase (GSH-Pox) and malondialdehyde (MDA) concentration as a biochemical markers of bystander effect were monitored for a period of 72 h. The DNA damage was measured by the comet assay. Micronucleus induction, mitotic index and cellular death as apoptosis or necrosis were simultaneously estimated, based on morphologic criteria. The bystander effect of irradiated cells on their neighbours was observed as a slight increase of MDA concentration, comparable decrease of GSH-Pox activity, and some fluctuation of mitochondrial and cytoplasmic isoenzymes of SOD. DNA strand breaks and rejoining measured by comet assay as mean tail length, demonstrated clearly the bystander effect for nontraversed radiation cells, additionally verified by tail moment. There was also a significant increase of micronucleation and apoptosis generated by radiation traversed cells in shielded neighbours. Furthermore, significantly higher increase of necrosis in shielded neighbour cells compared to radiation traversed cells was observed. Proliferative activity showed a suppression in both, radiation traversed and shielded neighbour cells in all measured time points. The behaviour of used parameters points to the radical nature of modificators secreted by radiation traversed cells inducing bystander toxic damage in shielded neighbour cells.

Photodynamic effects of two water soluble porphyrins evaluated on human malignant melanoma cells in vitro.

Two water soluble porphyrins: meso-tetra-4-N-methylpyridyl-porphyrin iodide (P1) and 5,10-di-(4-acetamidophenyl)-15,20-di-(4-N-methylpyridyl) porphyrin (P2) were synthesised and evaluated in respect to their photochemical and photophysical properties as well as biological activity. Cytotoxic and phototoxic effects were evaluated in human malignant melanoma Me45 line using clonogenic assay, cytological study of micronuclei, apoptosis and necrosis frequency and inhibition of growth of megacolonies. Both porphyrins were characterised by high UV and low visible light absorptions. Dark toxicity measured on the basis of the clonogenic assay and inhibition of megacolony growth area indicated that P1 was non-toxic at concentrations up to 50 microg/ml (42.14 microM) and P2 at concentrations up to 20 microg/ml (16.86 microM). The photodynamic effect induced by red light above 630 nm indicated that both porphyrins were able to inhibit growth of melanoma megacolonies at non-toxic concentrations. Cytologic examination showed that the predominant mode of cell death was necrosis.