Amorphous and crystalline cerium(IV) phosphates: biocompatible ROS-scavenging sunscreens.

This paper reports on a comprehensive study of the UV-shielding properties (namely, the sun protection factor and the factor of protection against UV-A radiation) and cytotoxicity (including photocytotoxicity) of amorphous and crystalline cerium(IV) phosphates. It has been shown that cerium(IV) phosphate NH4Ce2(PO4)3 is characterised by UV-shielding properties that are comparable to those of nanocrystalline TiO2 and CeO2. Moreover, cerium(IV) phosphates did not show toxicity towards cell cultures of NCTC L929 line mouse fibroblasts and human mesenchymal stem cells, in a wide range of concentrations, and even enhanced the proliferative activity of the latter. In a model study of the photoprotective properties of cerium(IV) phosphates on human mesenchymal stem cells, the pronounced protective effect of NH4Ce2(PO4)3 was observed, which was comparable to the shielding action of nanocrystalline CeO2. The results have shown that tetravalent cerium phosphates can be considered as promising UV-filters for sunscreen applications.

Nanoceria-curcumin conjugate: Synthesis and selective cytotoxicity against cancer cells under oxidative stress conditions.

A water- and alcohol-soluble cerium oxide-curcumin conjugate was obtained by co-evaporation with poly(N-vinylpyrrolidone) (PVP). A nanocomposite consisting of hybrid organic-inorganic particles was stable in a wide range of pH values. Its properties were evaluated using nine cell lines: normal (MDBK, ST, Vero) and malignant (L929, T98G, HEp-2, A549, RIN-m5F, Hep G2). PVP-stabilised nanoceria was shown to inhibit autoxidation of curcumin, to enhance curcumin photostability, to promote bioaccumulation and to affect curcumin cytotoxicity and photocytotoxicity, depending on cell type, being more toxic to cancer cells in a selective manner. Under the conditions of UVA/UVC or H2O2-induced oxidative stress, the nanoceria-PVP-curcumin (NPC) conjugate was found to possess a selective cytotoxicity: it caused drastic inhibition of metabolic activity or a decrease in the total number of tumour cells, while in non-transformed cultures under the same conditions, the nanoceria-PVP-curcumin conjugate protected cells from these damaging factors. The NPC-conjugate, unlike curcumin itself, demonstrated a photosensitising effect in tumour cell cultures, while protecting non-transformed cultures from the damaging effects of UV radiation or oxidative stress. Based on the results obtained, we strongly believe that this novel hybrid material has enhanced characteristics compared to other curcumin formulations, and can be considered as a potent drug for biomedical applications, including cancer therapy.

Photo-induced toxicity of tungsten oxide photochromic nanoparticles.

We synthesised a new type of photochromic tungsten oxide nanoparticles, analysed their photocatalytic activity and carried out a thorough analysis of their effect on prokaryotic and eukaryotic organisms. Ultrasmall hydrated tungsten oxide nanoparticles were prepared by means of hydrothermal treatment of tungstic acid in the presence of polyvinylpyrrolidone as a template, stabiliser and growth regulator. Tungstic acid was synthesised through an ion-exchange method using sodium tungstate solution and a strongly acidic cation exchange resin. Upon illumination, photochromic nanoparticles of WO3 were shown to increase greatly their toxicity against both bacterial (both gram-positive and gram-negative - P. aeruginosa, E. coli and S. aureus) and mammalian cells (primary mouse embryonic fibroblasts); under the same conditions, fungi (C. albicans) were less sensitive to the action of tungsten oxide nanoparticles. UV irradiation of primary mouse fibroblasts in the presence of WO3 nanoparticles demonstrated a time- and dose-dependent toxic effect, the latter leading to a significant decrease in dehydrogenase activity and an increase in the number of dead cells. WO3 nanoparticles were photocatalytically active under both UV light and even diffused daylight filtered through a window glass, leading to indigo carmine organic dye discolouration. The obtained experimental data not only show good prospects for biomedical applications of tungsten trioxide, but also demonstrate the need for clear control of biosafety when it is used in various household materials and appliances.

Panthenol-stabilized cerium dioxide nanoparticles for cosmeceutic formulations against ROS-induced and UV-induced damage.

A method of panthenol-stabilized cerium dioxide nanoparticles synthesis was developed and their effect on the survival rate of human epidermoid cancer cells HEp-2 and diploid epithelial swine testicular cell line (ST-cells) under oxidative stress conditions induced by hydrogen peroxide introduction and UV irradiation was studied. The results obtained indicate that the use of panthenol as a stabilizer supposedly provides a substantial increase in the efficiency of protection. The degree of protection is determined by panthenol-to-ceria molar ratio. The combination of panthenol and nano-ceria protects biological objects under study from reactive oxygen species (ROS) and UV-irradiation more effectively than individual panthenol or ceria. The protective action of panthenol-stabilized cerium dioxide nanoparticles depends strongly on their composition and the means of their application.

Antibacterial activity of cerium colloids against opportunistic microorganisms in vitro.

The CeO2 sol with the size of nanoparticles 2-4 nm has been synthesized. It has been determined that the synthesized nanocrystalline cerium has antibacterial activity in vitro against different groups of opportunistic microorganisms: clinical strains of Escherichia coli, Staphylococcus aureus and Candida albicans. The rate of viability depression of test-cultures depends on the concentration of cerium dioxide nanoparticles and time of incubation. It is shown that the sol interacts with the bacterial cell surface. It is suggested that the observed differences of antibacterial action of nanocrystalline cerium dioxide can be related to the structural characteristics of the cell surface.

UV-shielding property, photocatalytic activity and photocytotoxicity of ceria colloid solutions.

UV-shielding property, photocatalytic activity and cytotoxicity (including photocytotoxicity) of citrate-stabilized ceria colloid solutions were studied. It was established that UV-shielding property (namely, the sun protection factor, the critical absorption wavelength and the UVA/UVB-ratio) of ceria nanoparticles are as good as those of titanium dioxide and zinc oxide nanoparticles. It was further demonstrated that ceria nanoparticles possesses substantially lower photocatalytic activity, which additionally decreases upon decrease in ceria particle size. It was found that colloid ceria solutions are non-toxic to mouse fibroblasts (L929) and fibroblast-like cells of African Green monkey (VERO). Moreover, ceria nanoparticles are capable to protect these cells from UV-irradiation-induced damage. It was proposed that nanocrystalline ceria could be used not only as UV-blocking material, but also as prophylactic and even therapeutic compound for sunburns treatment.

[Nanocrystaline ceria based materials--perspectives for biomedical application].

Nanocrystalline ceria possesses a unique complex of physical and chemical properties making it highly bioactive material. In this review, modern data on the action of nanocrystalline ceria on cells, micro- and macroorganisms are analyzed. Special attention is paid to the analysis of the factors affecting protective properties of CeO2 with respect to the living systems.

[Antiviral effect of cerium dioxide nanoparticles stabilized by low-molecular polyacrylic acid].

Antiviral activity of nanosize cerium dioxide sols (CeO2) in animal cell culture has been studied. The inhibiting effect of the mentioned sols upon reproduction of vesicular stomatitis test-virus was demonstrated for the first time in case of preliminary 24-hour contact with cells lines L929 and EPT. The effectiveness of protective action depends on initial precursor and the way of obtained water nanosize nanosols.

Photodynamic activity of hematoporphyrin conjugates with gold nanoparticles: experiments in vitro.

AIM: To synthesize a conjugate of hematoporphyrin with gold nanoparticles, and to evaluate its photodynamic activity in experiments on cultures of transformed cells. METHODS: nanosized gold particles and nanocomposites synthesis methods, cell culture methods, photobiology methods, trypan blue dye exclusion test, chemiluminescence assay. RESULTS: Various hematoporphyrin-gold nanocomposites were obtained, which contained similar hematoporphyrin concentration (5 microg/ml) and varied concentrations (0.5-5 microg/ml) of gold nanoparticles with a diameter of 15 nm or 45 nm. It was established by chemiluminescence method that nanocomposites synthesized induce more efficiently the formation of photo-oxidative products than original photosensitizer. The experiments with transformed cell lines showed that photodynamic in vitro activity of synthesized hematoporphyrin-nanogold composites is much higher than that of the original photosensitizer. The better activity of the nanocomposites with gold particles of 45 nm vs such of 15 nm which was demonstrated in the experiments, can be apparently connected with the fact that bigger particles are able to transport more porphyrin molecules into malignant cells. CONCLUSION: The results obtained warrant the necessity of further studies with hematoporphyrin-gold nanocomposites in vivo on transplanted tumors of animals which have to define the real perspectives of the nanocomposites application in PDT.

[Antiendothelial antibodies in systemic scleroderma and Raynaud's disease]. / Antiéndotelial'nye antitela pri sistemnoi sklerodermii i bolezni Reino.

Using ELISA on fixed endothelial hybridoma (EAhy.926) cells we investigated the occurrence of antiendothelial antibodies (AEA) in the sera from patients with scleroderma systematica (SS) (n = 70) and Raynaud's disease (RD) (n = 19). The mean IgG and IgA-AEA levels were significantly higher in the SS patients than RD patients (p < 0.001) and controls (p < 0.001). We have detected circulating IgG-AEA in 64.2% of patients with SS, 35.2% of SS sera were positive for IgA-AEA. In patients with RD, the frequency of AEA corresponded to that of the random population sample. We have found a high incidence of Raynaud's phenomenon, myositis, telangiectasia and marked digital ischaemia (digital ischemic pulp ulcers, digital scars, osteolysis and autoamputation) among AEA positive patients with SS. AEA-positive patients were characterized by high extent and severity of Raynaud's phenomenon and higher average nailfold capillary microscopy scores. No correlations were found between AEA and different clinical or laboratory parameters, including the type of scleroderma (diffuse and limited), the presence of anti-Scl-7O and anticentromere antibodies and the clinical features of SS (lungs, kidneys and heart involvement, esophageal dysfunction, calcinosis, Sjogren's syndrome). There was no significant correlation between the AEA level and patient age, extent of skin involvement (skin score). Thus, in SS, AEA is associated with a peripheral vasculopathy and represent a useful marker for the diagnosis of endothelial dysfunction.

[The role of sympathetic reactivity in the development of Raynaud's syndrome]. / Rol' simpaticheskoi reaktivnosti v razvitii sindroma Reino.

Finger skin blood flow was studied in 131 patients with Raynaud's syndrome using laser Doppler flowmetry. Scleroderma systematica, systemic lupus erythematosus, rheumatoid arthritis, Sjogren's disease, mixed connective tissue lesions, Raynaud's disease were diagnosed in 61, 17, 10, 10, 10 and 13 examinees, respectively. Control consisted of 20 healthy subjects. The response of the blood flow was registered in response to functional tests activating sympathetic nervous system: indirect cooling, emotional stress, deep inhalation, Valsalva's test. Hyper-response to the above sympathetic stimulation was noted in none of the groups studied. In scleroderma systematica the reactivity significantly decreased with longer disease duration. It is clear that the study did not confirm the leading role of sympathetic hyperactivity in Raynaud's syndrome pathogenesis.

[The clinical significance of detecting the inhibition of topoisomerase I by the sera of patients with systemic scleroderma]. / Klinicheskaia znachimost' vyiavleniia ingibirovaniia topoizomerazy I syvorotkami bol'nykh sistemnoi sklerodermiei.

Topoisomerase I activity was studied by electrophoresis in agarose gel according to plasmid DNA relaxation. Sera from 62 patients with systemic scleroderma, 35 with Raynaud's syndrome, 8 with focal scleroderma, 15 with systemic lupus erythematosus, 20 with rheumatoid arthritis and 20 healthy subjects were examined. Out of 62 sera from SSD patients, anti-topoisomerase activity was found in 67.8% of cases. The test appeared positive in 79% of patients with diffuse and 63% with limited disease patterns. The mean age and disease standing were similar in the positive and negative groups. An increase of the skin count and more frequent occurrence of trophic disorders in patients with inhibition of the enzyme were recorded. 40% of the patients demonstrated the coincidence of the results with the use of the topoisomerase test and ELISA. In patients with other rheumatic diseases and in the healthy subjects, no inhibition of the enzyme was found.

[The use of Capoten in systemic scleroderma]. / Primenenie kapotena pri sistemnoi sklerodermii.

Experience gained with the use of captopril has been summarized in 5 patients with sclerodermic renal crisis (true sclerodermic kidney) as well as the results of the double blind clinical trial of captopril in 16 patients with Raynaud's syndrome. Captopril given for a long time in the dose 75-150 mg to the patients with true sclerodermic kidney turned out effective which showed up by a decline and stabilization of arterial pressure, decrease of the intensity of azotemia and headaches, and stabilization of renal function. No convincing data have been obtained, that may confirm a beneficial effect of captopril on Raynaud's syndrome. The drug was applied in a dose of 37.5 mg for 2 weeks.

[The total proteolytic and collagenolytic activity in the blood cells of patients with systemic scleroderma]. / Izuchenie obshchei proteoliticheskoi i kollagenoliticheskoi aktivnosti v kletkakh krovi bol'nykh sistemnoi sklerodermiei.

Collagenolytic (CA) and neutral caseinolytic activity (NCA) was studied in extracts from blood cells (neutrophils, mononuclear cells and platelets) of patients suffering from systemic scleroderma (SSD). 23 persons were examined. Of these, 15 had local skin lesions, 8 diffuse lesions. CA, both specific and per 10(6) cells was found to be dramatically decreased (2-4-fold) in all blood cells, whereas NCA was increased in neutrophils and mononuclear cells; in platelets, it remained within normal. The amount of protein in neutrophils and mononuclear cells was lowered 1.2 and 2-fold respectively. In diffuse skin lesions, the amount of protein in cells was lower than in local lesions. It should be noted that in SSD patients examined, the inflammatory process was unmarked. Therefore, the data on substantial changes in proteolytic activity cannot be related to the inflammatory process. A reverse correlation was established between CA in neutrophils and circulating immune complexes as was a reverse correlation between CA in mononuclear cells and blood antinuclear factor. The data presented indicate that proteinases are an important factor of the pathogenesis in SSD. Apparently, SSD is characterized not only by enhanced synthesis of collagen but also by a dramatic reduction of the activity of enzymes that specifically hydrolyze this group of proteins, which leads to a decrease of collagen catabolism and hence, to the development of fibrosis in tissues.

[The clinical value of determining beta-glucuronidase activity in the cells and blood serum of patients with systemic scleroderma]. / Klinicheskoe znachenie opredeleniia aktivnosti beta-gliukuronidazy v kletkakh i cyvorotke krovi bol'nykh sistemnoi sklerodermiei.

The spectrophotometric method was used to determine the activity of beta-glucuronidase (BGU) in the cells (neutrophils, mononuclear cells, thrombocytes) in the blood serum of patients with systemic sclerodermia (SSD). The authors revealed a synchronous change in the activity of BGU in all the cells and in the blood serum, and also a decrease in the activity of the enzyme in the concentration of protein in neutrophils, it being very significant in patients with SSD accompanied by trophic changes. There was a direct relationship between the activity of BGU in the blood serum and the level of C-reactive protein and an inverse one between the activity of BGU and the content of circulating immune complexes in the blood. The level of BGU in the blood serum reflects not only the activity of the inflammatory process but also the markedness of trophic changes in patients with SSD.

[A study of Raynaud's syndrome using dynamic infrared thermography]. / Issledovanie sindroma Reino s pomoshch'iu dinamicheskoi infrakrasnoitermografii.

The method of infrared thermovision was used to study 22 patients with Raynaud's syndrome: 9 patients with sclerodermia, 8 with the primary Raynaud's syndrome and 5 patients with various rheumatic diseases. Patients with recurrent Raynaud's syndrome exhibited adaptation disorders, anomalous distribution of temperature--warming up began not from the distal regions of the bones, as it happens in the norm and with the primary Raynaud's syndrome, but from the proximal regions. Functional tests for sympathetic activation showed the absence of excess reaction in all the groups under examination. Direct cooling of the hand in patients with recurrent Raynaud's syndrome was accompanied by a considerable delay in restoration of the initial temperature. Sublingual administration of nifedipine did not induce a rise in skin temperature in 6 out of 9 patients with sclerodermia. Marked disorders in microcirculation in patients with recurrent Raynaud's syndrome were observed. The role of injury inflicted to arteriovenous anastomoses in pathogenesis of the mentioned syndrome are discussed.

[The effect of dimethyl sulfoxide on the thromboelastographic indices and the microcirculation in patients with rheumatic diseases]. / Vliianie dimetilsul'foksida na tromboélastograficheskie pokazateli i mikrotsirkuliatsiiu u bol'nykh revmaticheskimi zabolevaniiami.

Using a blind method for assessing the results, a study was made of the effect of dimethylsulfoxide (DMSO) on fibrin formation and microcirculation in 42 patients with rheumatic diseases (rheumatoid arthritis, systemic scleroderma, Raynaud's syndrome). It has been shown that the therapeutic effect of DMSO in rheumatic diseases is determined to a definite degree by its normalizing action on fibrin formation and microcirculation.

[Treatment of Raynaud's syndrome in systemic connective tissue diseases with calcium antagonists]. / Lechenie na sindrom na Raynaud pri sistemnite zaboliavaniia na suedinitelnata tukan s kaltsievi antagonisti.

The results of a short and a prolonged treatment of Raynaud's syndrome with calcium antagonists are presented. The efficacy of Nifedipin, Verapamil and Fendiline was evaluated in a 14 day treatment of 61 patients with Raynaud's syndrome. Nifedipin and Fendiline was evaluated in a 14 day treatment of 61 patients with Raynaud's syndrome. Nifedipine and Fendiline were most efficient but Fendiline led to more untoward reactions. Verapamil was least efficient and exerted a weak vasoactive action. The influence of the hemocirculation indices on all drugs studied was insignificant. 20 patients with systemic sclerodermia were given 30-60 mg Nifedipin daily in the course of one year and the frequency, duration and expression of the attacks of Raynaud's syndrome decreased practically twice. The study allows the recommendation of Nifedipin as the drug of choice for the treatment of Raynaud's syndrome in the systemic connective tissue diseases.

[Sjögren's syndrome in systemic scleroderma]. / Sindrom Shegrena pri sistemnoi sklerodermii.

Combined investigation of 43 patients with sclerodermia systematica (SSD) was conducted to detect Sjogren's syndrome (SS) and to study SSD association with SS. Four groups of patients were defined: with marked SS (10), primary SS (12), probable SS (13), and without SS manifestations (8). Comparative characterization has shown that SS is detected slightly more frequently in a chronic course of SSD, combines with manifestations of sclerodactyly, telangiectasia, calcinosis, however esophageal hypomobility, indurative skin changes and contractures which are typical of SSD, occur less frequently than in SSD patients without SS. SSD association with SS is characterized by polyarthralgia, arthritis, marked Raynaud's syndrome, the frequency and rather high RF titers, the detection of anti-Ro and anti-La, and a significant rise of the level of circulating immune complexes determined by SS influence. SS manifestations in SSD are retention pains in the parotid glands, signs of clearness on sialograms, periductal sclerosis in the form of rings in morphological investigation of the parotid glands.