A Novel Nanoconjugate of Landomycin A with C60 Fullerene for Cancer Targeted Therapy: In Vitro Studies.

INTRODUCTION: Landomycins are a subgroup of angucycline antibiotics that are produced by Streptomyces bacteria and possess strong antineoplastic potential. Literature data suggest that enhancement of the therapeutic activity of this drug may be achieved by means of creating specific drug delivery systems. Here we propose to adopt C60 fullerene as flexible and stable nanocarrier for landomycin delivery into tumor cells. METHODS: The methods of molecular modelling, dynamic light scattering and Fourier transform infrared spectroscopy were used to study the assembly of C60 fullerene and the anticancer drug Landomycin A (LA) in aqueous solution. Cytotoxic activity of this nanocomplex was studied in vitro towards two cancer cell lines in comparison to human mesenchymal stem cells (hMSCs) using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test and a live/dead assay. The morphology of the cells incubated with fullerene-drug nanoparticles and their uptake into target cells were studied by scanning electron microscopy and fluorescence light microscopy. RESULTS: The viability of primary cells (hMSCs, as a model for healthy cells) and cancer cell lines (human osteosarcoma cells, MG-63, and mouse mammary cells, 4T1, as models for cancer cells) was studied after incubation with water-soluble C60 fullerenes, LA and the mixture C60 + LA. The C60 + LA nanocomplex in contrast to LA alone showed higher toxicity towards cancer cells and lower toxicity towards normal cells, whereas the water-soluble C60 fullerenes at the same concentration were not toxic for the cells. CONCLUSIONS: The obtained physico-chemical data indicate a complexation between the two compounds, leading to the formation of a C60 + LA nanocomposite. It was concluded that immobilization of LA on C60 fullerene enhances selectivity of action of this anticancer drug in vitro, indicating on possibility of further preclinical studies of novel C60 + LA nanocomposites on animal tumor models.

Estimating the effectiveness of various methods of evacuation of kidney stones, on the basis of data obtained on percentage of "stone free" and recurrent stone formation.

Using the materials of more than 200 scientific papers of recent years in this review it has been carried out analysis of the effectiveness and also discussed the merits and demerits of various methods of treatment of urinary stone diseases (USD). With this purpose, for the first time it has been carried out analysis of treatment quality of USD using more important quantitative parameters of treatment efficacy: 1--percentage of "stone free"; 2--percentage of recurrent stone formation. It has been emphasized on the higher effectiveness of treatment in combination of the method of ESWL with the methods of ascending litholysis. It was shown that in order to solve problems such as etiology and pathogenesis of the disease, elaboration of quantitative risk factors of the disease, and search for effective measures on pro- and metaphylaxis of USD, and also elaboration of various (including therapeutics) medium and methods for complete and rapid evacuation of stones, it is needed to carry out intensively fundamental and applied researches in the field of urinary stone diseases.

Total blood and urine protein of urolithiasis patients with renal calculi of different chemical composition.

We determined total blood protein (TBP) and total urine protein (TUP) in healthy subjects and urolithiasis (UL) patients with renal calculi of different chemical composition: phosphate (CaP), oxalate (CaOx) and urate (HUr). We discussed the peculiarities of TBP and TUP distribution curves obtained and showed that the data on TBP and TUP do not make it possible to reliably single out patients with UL or determine the chemical composition of calculi in their kidneys. However, it was established that the comparison of TUP measurement results for UL patients using the Ponseau-S and sulfosalicylic acid methods makes it possible to reliably separate patients with Ca-containing calculi (CaP and CaOx) from those with HUr calculi. The explanation to this phenomenon using the data on the fractional composition of TUP and the organic matrix of those patients' calculi is given.

Physicochemical background for ambiguity of clinical recommendations in treating phosphate nephrolithiasis.

Efficiency of clinical recommendations for curing and prevention of phosphate nephrolithiasis founded on physicochemical investigations is unexpectedly low and apparently did not exceed 50%. We tried to consider possible physicochemical causes of this fact. For this purpose the influence of changes of urine pH and of calcium, phosphate and complexon concentrations on the probability of different precipitation phases of solid calcium phosphate has been reviewed. The importance of tendencies of changing the urine dynamic physicochemical parameters such as the precipitation induction period and the amplitude of urine pH variations in time has been shown. It was established that the probability of the existence of Ca3(PO4)2, Ca8H2(PO4)6.5H2O, CaHPO4.2 H2O and MgNH4PO4.6 H2O in urine depends on the time of its transition from the supersoluble state and is determined in the final analysis by the relationship of formation rates and solid phase dissolution rates. This was verified by experiments and by data obtained in the clinical laboratory.

[The phenotypes of blood haptoglobin in urolithiasis patients]. / Fenotipy gaptoglobina krovi u bol'nykh urolitiazom.

Haptoglobin Hp phenotypes were determined in 104 patients with uroliths of different chemical composition and in healthy controls. 98 patients showed one of the three main phenotypes Hp (1-1, 2-1, 2-2). Electrophoretic motilities of protein fractions Hp were found out for the main phenotypes. Hp was not registered or its fraction motility was distinct from the main phenotypes in 6 patients. Hp phenotypes distribution obtained for all the examinees was compared to that of the controls. For healthy and total group of urolithiasis patients, for healthy and having CaPi and HVr nephroliths, the difference was insignificant in contrast to CaOx stones the incidence of which grew in Hp 1-1 carriers (p < 0.05). In view of this, Hp 1-1 phenotype can indicate a risk of oxalate urolithiasis.

[Total urinary protein in different types of nephrolithiasis]. / Obshchii belok mochi pri razlichnykh vidakh nefrolitiaza.

In 26 healthy individuals and 114 patients with urolithiasis, total urine protein levels were measured in a single sample by using the stain ponceau S. The findings were statistically analyzed. The levels of the protein were found to be 27-80 mg/l in the healthy individuals, while the distribution of the data was asymmetric as viewed from high values. The patients with urolithiasis exhibited their protein levels according to the type of nephrolithiasis. Proteinuria was demonstrated to be less pronounced in patients with oxalate and urate nephrolithiasis than in patients with coral phosphate calculi. There was a substantial asymmetry in the distribution of total urine protein for all the examined groups of urolithiasis patients, as well as great dispersion values, which fails to regard the parameter alone as a diagnostic criterion for the type of nephrolithiasis. At the same time it was noted that simultaneous examination of the levels of total protein, uric acid, potassium, and sodium enabled the type of a concrement (oxalate or phosphate) to be in vivo estimated with approximately 85% probability.

Urine pH variation dynamics in healthy individuals and stone formers.

Urine pH density distribution curves have been obtained in groups of patients with concrements of various chemical compositions. Quantitative regularities for mixing chemical compounds in the concrements established by the infrared spectroscopic method have been shown to agree with urine pH distribution density (in time). Potential physicochemical mechanisms for the revealed generality are considered. In particular, it is indicated that urine pH variations display in the first approximation buffer effect of the concrement components. A Fourier analysis of pH variations in the homogeneous urine of healthy individuals and in the systems of urine versus concrement as a time function has been made. Urine pH variations observed have been shown to be approximated by the superposition of harmonic vibrations with a range of frequencies multiple of the diurnal one. It has been found that a distinctly pronounced and complicated gamut of pH fluctuations over the entire physiological range of values (i.e. 4.5-8.5) is typical of healthy individuals in contrast to the stone formers.

[The use of trimethine dye to stain proteins following cellulose acetate electrophoresis]. / Primenenie trimetinovogo krasitelia dlia okrashivaniia belkov posle élektroforeza na atsetate tselliulozy.

The synthetic trimethine stain PK-144 is recommended for staining the biological fluid proteins after electrophoresis in cellulose acetate films. A good correlation of the values of protein fraction composition determined with the use of this stain and Ponso S stain was observed. The trimethine stain is highly sensitive and may be used in serial electrophoresis analyses in laboratory studies.