Photosensitizing effects and physicochemical properties of chlorophyll a derivatives with hydrophilic oligoethylene glycol fragments at the macrocycle periphery.

In this work, screening studies of the cytotoxic effect of chlorins with fragments of di-, tri-, and pentaethylene glycol at the macrocycle periphery in relation to HeLa, A549, and HT29 cells were performed. It is shown that, despite different hydrophobicity, all the compounds studied have a comparable photodynamic effect. The conjugate of chlorin e6 with pentaethylene glycol, which has the lowest tendency to association among the studied compounds with tropism for low density lipoproteins and the best characteristics of the formation of molecular complexes with Tween 80, has a significant difference in dark and photoinduced toxicity (ratio IC50(dark)/IC50(photo) approximately 2 orders of magnitude for all cell lines), which allows to hope for a sufficiently large "therapeutic window". A study of the interaction of this compound with HeLa cells shows that the substance penetrates the cell and, after red light irradiation induces ROS appearance inside the cell, associated, apparently, with the photogeneration of singlet oxygen. These data indicate that photoinduced toxic effects are caused by damage to intracellular structures as a result of oxidative stress. Programmed type of cell death characterized with caspase-3 induction is prevailing. So, the conjugate of chlorin e6 with pentaethylene glycol is a promising antitumor PS that can be successfully solubilized with Tween 80, which makes it suitable for further in vivo studies.

[Mineralogical composition of urinary stones, risk factors and metabolic disturbances in patients with calcium-oxalate urolithiasis].

AIM: To identify the most likely metabolic disturbances and risk factors for stone formation in a group of patients with calcium oxalate urolithiasis, and to establish the relationship between the mineralogical composition of calculi and impaired excretion of inhibitors and promoters of stone formation. MATERIALS AND METHODS: Fifty patients with calcium oxalate urolithiasis were tested using a complex of physicochemical methods. Patients assessment included evaluation of quantitative mineralogical composition of calculi, daily urine pH profile and daily urinary excretion of urates, calcium, magnesium, oxalate, phosphate and citrate ions. RESULTS: The main mineralogical phase of the stones in over 80% of patients was calcium oxalate monohydrate; none of the patients had pure dihydrate stones. The most frequent metabolic disorders were hypocitraturia, hypercalciuria and hyperuricosuria. Predominant risk factors were excessive body weight and insufficient fluid intake. Only one patient had an idiopathic stone formation. It was established for the first time that patients with calcium oxalate stones, containing 10 or more mass percent of apatites had statistically significantly lower daily urinary calcium and oxalate excretion and simultaneously increased phosphate excretion. CONCLUSIONS: The study findings showed that patients with calculi based on calcium oxalate dihydrate should undergo testing for daily urinary excretion of calcium and citrate while pa-tients with calcium oxalate stones containing 10 or more mass percent of apatites should also be tested for daily phosphate excretion and urine pH-profile. Daily urinary citrate excretion was reduced in all study patients, and urate excretion was significantly increased, apparently due to an imbalanced diet and excessive intake of animal protein. Menopausal and postmenopausal women are at a particular risk due to low urinary citrate excretion and high urinary calcium excretion regardless of stone composition.

[Quantitative mineralogical analyzes of kidney stones and diagnosing metabolic disorders in female patients with calcium oxalate urolithiasis].

OBJECTIVE: To conduct a complex examination of female patients with calcium oxalate urolithiasis to detect metabolic disorders, leading to stone formation. MATERIALS AND METHODS: The study was carried out using complex physical and chemical methods, including quantitative X-ray phase analysis of urinary stones, pH measurement, volumetry, urine and blood spectrophotometry. RESULTS: Quantitative mineralogical composition of stones, daily urine pH profile, daily urinary excretion of ions of calcium, magnesium, oxalate, phosphate, citrate and uric acid were determined in 20 female patients with calcium oxalate stones. DISCUSSION: We have shown that most of the stones comprised calcium oxalate monohydrate or mixtures of calcium oxalate dihydrate and hydroxyapatite. Among the identified abnormalities, the most frequent were hypocitraturia and hypercalciuria - 90 and 45%, respectively. Our findings revealed that the daily secretion of citrate and oxalate in patients older than 50 years was significantly lower than in younger patients. SUMMARY AND CONCLUSION: In conclusion, daily urinary citrate excretion should be measured in female patients with calcium oxalate stones. This is necessary both to determine the causes of stone formation, and to monitor the effectiveness of citrate therapy.

[Quantitative mineralogical analysis and structure of urinary stones in patients living in Ivanovo region].

This paper focuses on developing and implementing a method of quantitative mineralogical analysis of urinary stones based on powder diffraction data analysis using 4 Topas (Bruker) software. Mineralogical composition of 100 urinary stones from urolithiasis patients living in Ivanovo region was examined. More than 70% of stones consisted of calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD), and their mixtures with hydroxylapatite. Forty four percent of urinary stones consisted of one component (COM, uric acid (UA) or, less frequently, hydroxyapatite (HA); 56% of urinary stones comprised two, three or four components. The most common mineral was COM (more than 70% of cases), the rarest were calcium oxalate trihydrate (CT), brushite and newberrite. The most common combinations of minerals in mixed stones were COM+HA, COM+COD and COM+COD+HA. The texture, the surface composition and its changes in the course of chemolysis in different types of stones were examined using scanning electron microscopy (SEM) and X-ray microanalysis (XRM). Implications for using analytical chemical and physical techniques for the diagnosis and treatment of urolithiasis were discussed.

[DIAGNOSIS OF METABOLIC DISORDERS AND METAPHYLAXIS OF RECURRENT CALCIUM OXALATE UROLITHIASIS].

The paper presents the results of the 1-year screening of biochemical parameters of urine in female patient with recurrent calcium urate urolithiasis. Based on the data of quantitative X-ray phase analysis of the composition of stone and a complex of clinical and laboratory examination, reasons for recurrent stone formation were determined. The main reasons included hypocitraturia, hyperosmolarity of urine and uric acid diathesis. Therapy with citrate mixtures and adequate water schedule (daily urine--2-2.5 liters) for 10 weeks allowed to increase the urinary pH, led to 2.5-fold increase in daily urinary citrate excretion and getting rid of residual stones in both kidneys. The effect of citrate therapy lasted for a further six months after drug withdrawal. Subsequently, the daily urinary citrate excretion and pH decreased, but even after 8 months remained still above baseline values. Obviously, for high risk patients it is necessary to define the daily excretion of citrate, and diagnosis of hypocitraturia requires long course therapy with citrate mixtures, with a break ofnot more than six months and obligate maintenance of adequate diuresis.

[A triple system water-urea-L-alpha-alanine. Thermodynamic properties and intermolecular interactions].

The heat of the dissolving of L-alpha-alanine at 293, 298, 306, and 318K in aqueous solutions of urea in the concentration range 0-7 mol urea/kg water has been determined by the microcalorimetric method. It was found that the heat of the dissolving of the amino acid linearly depends on the square root of the molality of the urea solution. It was shown that the enthalpy and entropy of the transfer of L-alpha-alanine from water into an aqueous solution of urea do not depend on temperature, and the heat capacity of transfer is equal to zero. An almost complete enthalpy-entropy compensation was noted. It was shown that the parameter characterizing the changes in the effective Gibbs energy of the dissolving of L-alpha-alanine in water and aqueous urea solutions has negative values due to the dominant entropy component. The system water-urea-L-alpha-alanine becomes less structured with increasing temperature and more structured as the urea concentration increases.

[Effects of hydrophilic and hydrophobic hydration in tetramethylbisurea and N,N'-dimethylpropyleneurea solutions].

The thermal effects of dissolving tetramethylbisurea in water at 298-318 K and N,N'-dimethylpropyleneurea at 293-313 K have been measured. It was shown that the standard heat of dissolution of tetramethylbisurea at 298 K was 3.58 +/- 0.04 kJ/mol, and that of N,N'-dimethylpropyleneurea was 22.8 +/- 0.01 kJ/mol. The standard heat capacities of urea derivatives at 298 K differed insignificantly: 167 +/- 10 J/(mol x K) and 149 +/- 5 J/(mol x K) for tetramethylbisurea and N,N'-dimethylpropyleneurea, respectively, indicating the moderately hydrophobic character of hydration of these compounds. It was found that, at temperatures close to the temperature of maximum density of water (277 K), the temperature dependence of Gibbs energy for tetramethylbisurea goes through the maximum.