STED properties of Ce3+, Tb3+, and Eu3+ doped inorganic scintillators.

Scintillator-based X-ray imaging is a powerful technique for noninvasive real-space microscopic structural investigation such as synchrotron-based computed tomography. The resolution of an optical image formed by scintillation emission is fundamentally diffraction limited. To overcome this limit, stimulated scintillation emission depletion (SSED) X-ray imaging, based on stimulated emission depletion (STED) microscopy, has been recently developed. This technique imposes new requirements on the scintillator material: efficient de-excitation by the STED-laser and negligible STED-laser excited luminescence. In this work, luminescence depletion was measured in several commonly-used Ce3+, Tb3+, and Eu3+ - doped scintillators using various STED lasers. The depletion of Tb3+ and Eu3+ via 4f-4f transitions was more efficient (Ps = 8…19 mW) than Ce3+ depletion via 5d-4f transitions (Ps = 43…45 mW). Main origins of STED-laser excited luminescence were one- and two-photon excitation, and scintillator impurities. LSO:Tb scintillator and a 628 nm cw STED-laser is the most promising combination for SSED satisfying the above-mentioned requirements.

[Family diabetes and its consequences in cancer patients].

Preliminary data are confirmed on the more rare prevalence of family history of diabetes mellitus (DM) in cancer patients, mainly females, with diabetes in comparison with diabetics without cancer pathology. Familial diabetes does not worsen additionally tumor characteristics against the same in patients with non-familial diabetes. More than that, familial diabetes in diabetics with breast cancer goes together with lesser size of tumor and demonstrates an inclination to the rarer distant metastases in breast and endometrial cancer patients. The signs of systemic DNA damage (evaluated, in particular, on the basis of 8-OH-dG serum levels) are pronounced in postmenopausal diabetic cancer patients with familial diabetes in lesser degree than in non-familial variant of DM. In toto, this allows to consider family history of DM in patients with type-2 diabetes as a particular factor of tumor growth containment, which mechanisms and causes, warrant further studies.

[Dynamics of parameters of systemic inflammation and hemocoagulation in early postoperative period in patients with heart valve prostheses].

In 42 patients with rheumatic heart defects before implantation of mechanical valves and on days 5 and 20 after surgery we measured parameters of hemostasis, levels of proinflammatory cytokines (interleukin 6 [IL-6], tumor necrosis factor- [TNF-] and C-reactive protein [CRP]) as well as activity of enzymes (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatine phosphokinase and its MB fraction). On day 5 after surgery we revealed substantial elevation of IL-6, TNF-, and CRP levels, increase of activity of the studied enzymes, contents of fibrinogen and soluble fibrin monomer complexes (SFMC), and to the contrary lowering of antithrombin III level and decrease of number of platelets. On day 20 IL-6 and TNF- levels remained significantly elevated compared to preoperative values. Concentrations of enzymes and parameters of hemostasis returned to baseline values while content of SFMC remained significantly decreased. In early postoperative period levels of IL-6 and TNF- significantly correlated with that of SFMC and platelet count what reflected interrelation ship of processes of inflammation and coagulation. Severity of systemic inflammatory reaction in patients with implanted prosthetic valves influenced optimal doses of warfarin.

[Comparison of results of elastography with hormonal and metabolic status in patients with the diagnosis of thyroid neoplasms].

In order to assess the effectiveness of compression elastography of the thyroid gland as a method for differential diagnosis to studies conducted in the pre-operative period, there were involved 34 patients with a mean age 46.6 +/- 2.7 years. Elastography in the real time was characterized, according to the method of estimating, by a relatively high sensitivity (85.2-92.5%) and accuracy (70.6-79.4%), but low (30%) specificity. The specificity of the method, as it turned out, could be improved by taking into account the level of thyroid stimulating hormone (TSH) in the blood or body mass index (BMI) of the patients and, therefore, reducing the number of false-positive findings. Further improvement in the pre-operative diagnosis of malignant tumors of the thyroid gland and the formation of appropriate risk groups could be based on a combination of cytologic, hormonal, genetic and instrumental methods, including the so-called shear wave elastography.

[Hormonal-metabolic pattern of postmenopausal females with new onset of diabetes mellitus type 2: the role of cancer and hereditary predisposition to diabetes].

85 females were studied, 35 females had new onset of diabetes (DM2) and in 50 women DM2 was associated with recently diagnosed cancer (C+DM2). Group C+DM2 was characterized by higher levels ofbody mass index, insulinemia, estradiolemia, interleukin 6 in serum, and glyoxalase I activity in mononuclears. At the same time patients in C+DM2 group who had familial predisposition to DM2 were characterized by lower body mass index, body fat content, waist circumference, insulinemia, serum interleukin 6, viscosity of erythrocyte membranes and percent of comets in mononuclears in comparison with patients without familial predisposition to DM2. These trends were mostly opposite to the data of subgroups comparison (with or without relatives with DM2) in females with DM2 without cancer. The conclusion is made that the hereditary load with DM2 is differently realized in diabetics with higher or lower predisprosition to cancer that deserves further study.

[Potential sensitivity to metformin of the diabetics suffering and not suffering with cancer: a pharmacogenetic study].

The group (totally 156 postmenopausal women) used for the study of 'standard' (S) and 'associated' (A) genetic markers of potential sensitivity to metformin (MF) consisted of 37 healthy females, 32--with diabetes (DM) without cancer, 64 cancer patients with DM, and 23 cancer patients without DM. No significant difference in carrying of S-polymorphisms was found between DM patients without and with cancer. In cancer patients without DM most characteristic data regarding potential MF-response were detected with polymorphisms of STK11 gene while data on OCT1_rs622342 and OCT1_R61C variants showed opposite trends. In regard of A-markers, the tendency to the more often finding of GC genotype of OLR1_GS01C in DM patients carrying 'MF-positive' variant of OCT1_R61C deserves to be underlined. In patients with new-onset diabetes who carried S-markers of potential response to MF higher insulin resistance (OCT1_R61C and OCT1_rs622342) as well as lower estradiolemia (STK11 and C11orf65) were discovered. Thus, according to genetic S-criteria of sensitivity to MF, DM patients with and without cancer differ in lesser degree than they differ from cancer patients without DM. It can not be excluded, that The efficiency of such criteria might be increased due to combination with A-markers and certain hormonal-metabolic indices.

[Genetic testing of constitutive sensitivity to metformin in cancer patients with and without diabetes].

Metformin (MF) belongs to the most popular andidiabetic medicines and is considered to possess a selective antineoplastic action. This selectivity at least partly may be explained by the certain features of MF pharmacogenetics. More than 150 postmenopausal females divided into 4 groups (cancer +diabetes type 2 (DM2); cancer without DM2; DM2 without cancer, and healthy) were studied. Genetic polymorphisms of the two groups of genes--entitled on the basis of the relation to potential MF effect as a 'standard' (S) or 'associated' (A)--were under investigation. Among S-markers a most informative in regard of MF response prediction appeared to be polymorphisms of OCT1-R61C organic cation transporter protein 1 gene and serin/threonine kinase STK11. In the group of A-polymorphisms the GC genotype of oxidized lipoprotein receptor OLR1_G501C demonstrated tendency to the combination with 'MF-positive' variant of OCT1_R61C. The carriers of the latter were characterized with insulin resistance while carriers of STK11 variants--with lower blood estradiol level. Postmenopausal diabetics with as well as without cancer, differ in genetic markers of potential response to metformin less than they differ from cancer patients without DM2.

[The influence of metformin and N-acetylcysteine on mammographic density in postmenopausal women].

Mammographic breast density (MBD) value is currently one of the strong predictors for mammary carcinoma development. There are also other conditions predisposing to MBD increase with hormone-related markers different from those used in breast cancer, while pharmacological methods for MBD reduction are few and still considered experimental. In the current study 25 postmenopausal women received daily for a median 10.5 months 1-1.5 g of antidiabetic biguanide metformin (siofor) (n = 14) or 400-600 mg of antigenotoxic drug N-acetylcysteine (n = 11). In both groups MBD was measured before and after treatment. The effects of both drugs were quite similar. Metformin use lead to lower MBD in 4 of 14 (28.5%) women with mean MBD decrease of -1,24% (absolute dynamics) and -5.03% (relative value). In N-acetylcysteine group this effect was observed in 27.3% of cases, with -2.0% absolute dynamics and -6.1% relative dynamics. In metformin group the most evident absolute and relative dynamics was observed in patients with no signs of metabolic syndrome, -10.86% compared to -2.45%. In 7 women the metformin use also lead to decrease of dense and increase of non-dense areas on digital scans, leading to decrease in dense to non-dense area volume ratio. Therefore, the similar effects of metformin and N-acetylcysteine are probably explained mostly not by insulin resistance elimination by metformin, but by altered cell proliferation, apoptosis and DNA repair.

[Clinical significance of three-week thyroglobulin test in patients with thyroid cancer undergoing thyroidectomy].

High level of thyroglobulin (Tg) after thyroidectomy has been shown to be an early marker of either metastases or local recurrence of differentiated thyroid cancer (DTC). The aim of this study was to evaluate the relation between Tg level estimated on the third week after thyroidectomy and clinic-pathologic characteristics of DTC as a possible prognostic criterion used to mark the patients with radioiodine therapy indications. Research data on 45 patients (39 women, 6 men, age 22-75 years) with DTC and without high level of Tg autoantibodies have been included in the study. Eleven patients underwent surgical treatment due to disease recurrence. In all patients Tg and thyroid hormones levels were measured before the thyroidectomy and on the third week after it. The postoperative level of Tg as TTM coefficient (ratio of postoperative Tg to daily L-thyroxin dose in mcg to body weight in kg) was higher in patients with unfavorable prognosis: (a) capsular invasion, (b) cervical lymph nodes metastases, (c) advanced disease stage, (d) high risk of recurrence. The postoperative serum Tg levels were similar in primary disease patients and patients with DTC recurrence. There was no relation between preoperative Tg level and any prognostic factors although there was a tendency to higher (more than 2 ng/ml) Tg levels in patents with high preoperative Tg levels. Finally, the serum Tg level on the third week after thyroidectomy is a valuable prognostic criterion and can be used in DTC to determine the radioiodine therapy indications.

[Familial diabetes frequency as a factor in diabetics suffering from cancer].

Although type 2 diabetes contributes to the risk of development of certain tumors; factors which modify this relationship need to be further examined. Familial diabetes frequency was followed in (a) diabetes-free cancer patients (132), aged 60.3 +/- 1.2; (b) cancer patients with apparent (62.3 +/- 0.4; n=371) or occult type 2 diabetes (61.6 +/- 1.2; n=65) and (c) cancer-free patients with type 2 diabetes (61.8 +/- 0.4; n=237); the latter group (172 females and 65 males) featured almost identical diabetes frequencies: 30.8 +/- 3.5% and 30.8 +/- 5.7%, respectively. They significantly exceeded a relevant index occurring in families free from cancer concomitant with diabetes (6.1 +/- 2.1%). Significantly lower frequencies of familial diabetes were reported in cancer patients as compared with cancer-free patients (12.9 +/- 2.1% females, p < or = 0.01; 19.4 +/- 3.8% - males, p=0.1). To sum up, it cannot be ruled out that familial diabetes is a marker of relative decrease in potential risk of cancer rather than that of increase. The causes of this phenomenon and its possible dependence on gender need to be explored.

[Investigation of the association of mammographic breast tissue density with glucose effects and circulating stem cells].

Our study involving healthy postmenopausal females established that mammographic breast tissue density was lower in cases of more intensive stimulation by glucose of reactive insulinemia and glucose-induced glyoxalase I activity in bood mononuclears as well as in women with higher concentrations of circulating CD90+stem cells. Conversely, the density tended to increase in those with higher ratio of glucose-induced generation of reactive oxygen species in mononuclears. Our data point to possible mechanisms of increased density as a breast cancer factor when concomitant with relative predominance of progenotoxic effect of glucose and lower CD90+stem cells levels which are believed by some authors to be capable of suppressing the growth of certain tumors.

[Study of dual ("joker") function of glucose in cancer patients].

A relationship was studied between generation of glucose-induced reactive oxygen species capable of causing damage to DNA (genotoxic or G-effect) and insulin secretion (endocrine or hormonal effect - H-effect) in primary menopausal patients with endomrnetrial carcinoma (EC) (32) or colonic cancer (CC) (16). The study group was compared with healthy menopausal women (25) and patients with an impaired glucose tolerance (IGT) (21). Besides, we examined 32 menopausal patients (CC--6 and EC--26) more than 12 months after surgery. The following basic patterns were established: (1) H-effect was reported in EC-1 and 1GT groups nmore often than in healthy peers and those with EC-2: (2) G-effect tended to prevail in CC patients and those with EC-2 and in patients with EC-1 twelve months after operation; (3) G-effect occurred more often in primary EC patients, particularly, those with EC-2 (71%) and IGT (58%) (as compared with CC patients (33%) and healthy females (p < or = 0.001). It is suggested that a comparison of the two effects might provide a criterion for use of relevant means of prevention of certain malignancies or correction of disorders in cancer patients following radical treatment.

[Influence of metformin and N-acetylcysteine on hormonal and genotoxic effects of estrogens and glucose in convalescent cancer patients].

Our study involved 25 postmenopausal patients (endometrial carcinoma--16, breast (6) and colorectal (3) cancer, aged 56.8 +/- 0.9). All patients were in clinical remission. None had received any specific therapy for at least 12 months. After a laboratory endocrine-genotoxic switch evaluation, 17 patients were given an antidiabetic drug--biguanide metformin--or N-acetylcysteine as antioxidant (8) for 3 months. A checkup was carried out on completion of the course. As a result, hormonal and progenotoxic effects of glucose were found to be inhibited significantly. Much less pronounced was the impact on relevant effects of estradiol which were investigated vis-a-vis nature of blood mononuclear response in vitro. Both isolated and combined administration of said drugs used for endocrine-metabolic rehabilitation is justified.

[Diabetes mellitus and obesity: projection onto oncological morbidity].

Peculiar features of human morbidity and their changes in time are registered chronologically starting from the XVII-VYIIIth centuries. After the period of predominantly infectious diseases, chronic and non-communicable conditions continued to gain momentum in the last 3-5 decades. Side by side with AIDS, accidents, effects of smoking etc, the global epidemics of diabetes mellitus and obesity comes up to take a leading place in the general population morbidity. In this communication, possible causes of this situation and its possible association with cancer are considered based on the results of original studies. Measures for the prevention and treatment of these diseases are discussed.

[Autoantibodies to steroid-producing ovarian cells in cancer patients].

Our investigation included 158 women, aged 23-73: patients with tumors of the ovary, breast and endometrium--117 and subjects without oncological pathology--41. Autoantibodies to microsomal fraction of follicular ovarian cells (> 500 Unit/ml) in healthy subjects were revealed 8.3% while in patients with ovarian, breast and endometrial malignancies (without significant differences between benign and malignant tumors) in 33.30%, 45.60% and 25.0%, respectively. Higher level of anti-ovarian autoantibodies involved an inverse correlation between blood levels of FSH and estradiol in ovarian and endometrial carcinoma patients. It also co-occurred with a tendency of increasing levels of autoantibodies to thyroglobulin. Whatever apparent predictive accuracy in oncological clinic, high concentrations of anti-ovarian autoantibodies point to certain shifts taking place in the formation of reproductive system pathology. Besides, they may have considerable prognostic significance.

[The dual (joker) function of glucose: study of its association with aging and glucose metabolism disorders].

Relation was studied between generation of glucose-induced reactive oxygen species (ROS), which appear to be related to DNA damage (genotoxic effect, G), and insulin secretion (endocrine or hormonal effect, H) in women of different ages (one group under 45 and the other one over 45; n=25 and n=14, respectively). The healthy women in those two groups were compared with patients in whom we had found an impaired glucose tolerance (IGT) or type 2 diabetes mellitus (DM) (n=17, mean age 57.3 +/- 2.7). The hormonal effect of glucose was more pronounced in the senior group, and especially in group with IGT, if compared with the younger group. Genotoxic effect of glucose was discovered more frequently in the younger group, mainly in smoking women. Comparison of G/H effects showed that the evaluation of glucose-induced genotoxity (GIGT) was more frequent in the IGT group than in the senior group (p < 0.05). No difference was detected in the GIGT frequency values in the two healthy groups. It may therefore be concluded that GIGT did not increase within the ambit of ageing studied in this work, while it increased in the IGT group. It is possible that the high frequency of the G effect in the IGT group could be a marker of oxidative stress and/or predisposition to complications in DM. The dual (joker) function of glucose and the prevalence of G effects over H effects may be of use in choosing the method of correction for each particular case.

[Endocrine-genotoxic switchings as promoter of main noninfectious diseases].

Peculiarities of the incidence and spread of main non-infectious diseases (MNID) are in one or another way connected with the conception of "normal" and "successful" aging. The age-related increase in the frequency of MNID, associated with estrogen deficiency or excess, can be explained by the presence of estrogen effect switching phenomenon. The increase in the genotoxic effect of estrogens, isolated or combined with the weakening of the hormonal effect, can worsen the clinical course of MNID (including malignant tumors of hormone-dependent tissues). The effects of two other endocrine-genotoxic switchings (the joker function of glucose and adipogenotoxicosis) may realize in the same direction. The three mentioned phenomena form the so called basic triad, separate elements of which can interact. Endocrine-genotoxic switchings and their inductors are targets for prophylactic measures and, possibly, therapeutic ones. Both approaches may be divided into several groups with different points of application, whereas their ultimate goal is optimal balance between hormonal and DNA-damaging effects of estrogens, glucose, and adipose tissue-associated factors.

[Polymorphism of glucose intolerance and insulin resistance susceptibility genes in oncological patients].

Glucose intolerance and insulin resistance belong to the group of leading risk factors for breast (BC) and endometrial cancer (EC). Differences in the intensity of association of these endocrine disturbances with BC and EC may at least partly be explained by non-identity in polygenic nature of the mentioned hormone-metabolic shifts and oncological diseases themselves as well. In this study, which included 105 healthy postmenopausal women and 301 female cancer patients (110 BC and 191 EC) without overt diabetes mellitus, we compared the frequency of the following genetic polymorphisms: insulin receptor substrate-1, IRS Gly972Arg; leptin receptor, LEPR Lys109Arg and Gln223Arg; mitochondrial uncoupling protein-2, UCP2_866G/A; and gene ND3 of mitochondrial DNA, mtDNA 10398A/G. Genotyping was performed with allele-specific real-time PCR. According to data received, certain genetic markers associated with impaired glucose tolerance and/or insulin resistance (namely, leptin receptor genotypes 223 Gln/Arg and Gln/Gln) are revealed in oncological patients more often than in females without cancer. Other markers (like genotype UCP2 866AA and polymorphism mtDNA 10398A) appeared to be relatively more frequent in EC than in BC providing one of the interpretations for the lower insulin sensitivity and higher incidence of carbohydrate metabolism disturbances in the first of these two diseases.

[Breast cancer receptor status in smoking and diabetic patients].

Estrogen (ER) and progesterone (PR) receptor levels were assayed in 2,284 primary breast cancer patients who either smoked (350) or suffered diabetes mellitus type 2 (1997-2003). In a group of 1010, 95 patients had diabetes mellitus type 2 whereas 393--such signs of cardiovascular pathology as atherosclerosis, arterial hypertension and ischemic heart disease (2000-2003). Among the premenopausal smokers, the ER+PR-phenotype predominated (t = 2.18, p < 0.05) as well as among the diabetics (t = 2.01, p < 0.05). In reproductive diabetics, the share of PR- tumors was significantly higher than in diabetes-free patients (t = 2.17, p < 0.05). There was no correlation between diabetes and the tumor receptor phenotype in the menopausal group, while ER + tumors--occurred more frequently in smokers (t = 2.33, p = 0.02). There was no link between cardiovascular pathology and receptor status in either of the age groups. Hence, the increasing proportion of ER + PR--tumors in smokers and diabetes mellitus patients occurs in a random manner in menstruating women, which is associated with elevated estrogenemia. This indicates the phenomenon of switching of estrogen effects involving disturbed transduction of estrogen signals.

[Comparison of letrozole and exemestane used in non-adjuvant therapy of endometrial carcinoma].

The clinical and endocrine-related effects of 2-week preoperative treatment of endometrial carcinoma patients with a non-steroid inhibitor of letrozole aromatase (femara 2.5 mg/day, n=10) and a steroid inactivator of the enzyme (exemestane 25 mg/day, n=13) were compared. In the first group, pain relief in the lower part of the belly and/or decreased uterine discharge were reported in two cases, as well as a 31% drop in the mean endometrial M-echo (ultrasound) signal. In the exemestane group, two patients revealed moderate uterine discharge decrease matched by a 15.6% decrease in M-signal intensity; no tumor was detected in another patient on completion of the course. Letrozole effect was relatively greater when such parameters as tumor-tissue aromatase level, estrogen concentration in vaginal smear and blood-cholesterol, FSH and LH levels were taken into consideration. However, exemestane therapy involved a relatively sharper drop in the levels of tumor receptors of progesterone and a significantly higher estrogen/progesterone receptor ratio. Hence, no matter how short treatment duration was, both steroid and non-steroid aromatase inhibitors induced effects predominantly associated with lowering estrogen production in endometrial carcinoma patients. This makes a case for further clinical trials of these drugs to deal with the pathology.