[Left and right ventricular diastolic dysfunction in patients with early rheumatoid arthritis before prescribing disease-modifying antirheumatic therapy].

AIM: To estimate the rate of diastolic dysfunction (DD) of the left and right ventricles (LV and RV) in patients with early rheumatoid arthritis (RA) before using disease-modifying antirheumatic drugs (DMARDs) therapy and to investigate its association with traditional risk factors (TRFs) for cardiovascular diseases (CVD) and inflammatory markers. SUBJECTS AND METHODS: The investigation enrolled 74 patients with a valid diagnosis of RA, including 56 (74%) women (median age, 54 years; disease duration, 7 months); the patients who were seropositive for rheumatoid factor (RF) (87%) and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies (100%) who had not been on DMARDs or glucocorticosteroids. TRFs for CVD and carotid artery atherosclerosis were assessed from duplex scanning data and echocardiography was performed in all the patients with early RA before starting the therapy. The ratio of the maximum blood flow velocity during early diastolic filling (E) to that during atrial systole (A) was used as a criterion for LVDD and RVDD. There were 3 types of impaired ventricular filling: 1) E/A <1; 2) E/A = 1-2; 3) E/A > 2. RESULTS: LVDD and RVDD were detected in 35 (48%) and 17 (23%) patients, respectively. RVDD was recorded only in conjunction with LVDD. Among LVDD and RVDD, the former was prevalent. All the patients with early RA were divided into 3 groups: 1) patients with LVDD and RVDD; 2) those with LVDD; 3) those without ventricular DD. All the three groups were matched for the level of DAS28, anti-CCP antibodies, and RF. The incidence of arterial hypertension, dyslipidemia, and abdominal obesity was higher in the patients of Groups 1 and 2 than in those of Group 3. There was a progressive decrease in high-density lipoprotein (HDL) cholesterol concentrations and increases in triglyceride (TG) levels and atherogenic index from Group 3 to Group 1, with the concentrations of total cholesterol and low-density lipoprotein cholesterol being similar in the 3 groups. Coronary heart disease was recorded more frequently in Group 2 than in Group 3. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) proved to be also significantly higher in the patients with DD than in those without DD. Correlations were found between LV E/A and ESR, CRP, HDL cholesterol, TG, RV E/A and ESR, DAS28, TG. CONCLUSION: The patients with early-stage RA were found to have high incidence rates of LVDD and RVDD, which is related to the high prevalence of CVD, the high spread of TRF for CVD, and the high activity of an inflammatory process.

Fluorescent diagnosis and photodynamic therapy for C6 glioma in combination with antiangiogenic therapy in subcutaneous and intracranial tumor models.

OBJECTIVE: Investigating the distinctions pharmacokinetics of chlorin e6 conjugated with polyvinyl pyrrolidone photosensitizer (Ce6CPPPS)in healthy and tumor tissues of rat brain and evaluating the antitumor efficacy of combination treatment for C6 rat glioma including photodynamic (PDT) and antiangiogenic therapy (AAT). MATERIALS AND METHODS: The study was performed on 50 white random-bred rats in subcutaneous and intracranial models of C6 glioma. Photosensitizer (PS) Ce6CPPPS single injection at a dose of 2.5 mg/kg was made into the animal's caudal vein. The PS accumulation level in brain tissues and C6 rat glioma was measured with spectral fluorescence technique using LESA-01-Biospek spectrum analyser (Russian Federation, Moscow; λ = 632.8 nm). Photoirradiation of intracranial and subcutaneous C6 glioma was carried out with a light exposure dose of 50 J/cm(2) (IMAF-Axicon, Republic of Belarus; λ = 661 nm). AAT drug bevacizumab, single injection was made intravenously at a dose of 10 mg/kg 24 h after tumor photoirradiation. The criteria for efficacy evaluation were mean survival time (MST) and median survival of the animals in the study group vs the control and the -percentage of tumor necrosis areas induced by the above-mentioned treatment. RESULTS: The optimal time for photoirradiation of intracranial C6 glioma is 0.5 h after Ce6CPPPS injection. The combination therapy group demonstrated a statistically significant MST increase (38.4 ± 4.39 days) compared with the PDT group (29.2 ± 3.5 days) (p = 0.02) and the AAT group (27.1 ± 2.74 days) (p = 0.02). Necrosis areas in tumor tissue were as follows: the intact control - 10.0 ± 2.55%, PDT - 54.87 ± 6.95% (p = 0.003), AAT - 57.83 ± 6.53% (p = 0.003) and combination therapy - 89.43 ± 5.57% (p = 0.001). CONCLUSIONS: This paper is the first report about feasibility of efficient use of PDT with a PS of chlorin series and AAT with bevacizumab for the treatment of brain tumors in experimental models.

Effects of combined sonodynamic and photodynamic therapies with photolon on a glioma C6 tumor model.

UNLABELLED: The aim of this study was to investigate the low-power density sonication, sonodynamic therapy (SDT) with Photolon and combination of SDT and photodynamic therapy (PDT) with Photolon for the ablation of glioma C6 tumor model in rats. METHODS: The study was performed on 50 rats bearing glioma C6. The tumors were sonicated with/without prior intravenous injection of photosensitizer (PS) Photolon (2.5 mg/kg b.w). Sonication was performed with 0.4; 0.7 and 1.0 W/cm² power density at 1 MHz frequency for 10 min, 2.0 h after Photolon administration using BTL-5710 Sono (BTL Industries Limited, Great Britain). PDT was carried out 2.5 h after Photolon administration using diode laser with 661 nm wavelength (IMAF-AXICON, Minsk, Republic of Belarus) at doses of 50 and 100 J/cm² with 0,17 W/cm² fluence rate. Assessment of tumor response was performed by vital staining with Evans blue and pathologic examination. RESULTS: The maximal tumor necrosis area that underwent sonication (1 MHz; 0.7 W/cm²; 10 min.) followed by PDT at a dose of 100 J/cm² was 100%. CONCLUSION: This is the first report to demonstrate the benefits of sono-photodynamic therapy (SPDT) consisting of low-power density ultrasound and PDT for the treatment of malignant glioma models.

Photolon enhancement of ultrasound cytotoxicity.

OBJECTIVE: To evaluate the impact of Photolon on cytostatic and cytotoxic effects of therapeutic range ultrasound in C6 glioma cells. METHODS: C6 glioma cells in suspension or monolayer cell culture were exposed to ultrasound (880 kHz, 0.2-0.7 W/cm2) in the presence or absence of Photolon at the concentration of 1 µg/ml in the culture medium, and then cell viability was evaluated. RESULTS: Photolon increased the cytotoxic effect of ultrasound by 1.5-2.3-fold but had no effect on its cytostatic activity. CONCLUSION: Photolon produces a pronounced sonosensitizing effect on glioma C6 cells and is a promising drug for sonodynamic treatment of malignant tumors.

The effect of cytostatics and hyperthermia on RAJI human lymphoma cells.

AIM: To evaluate the effect of hyperthermia on cytostatic activity of chemotherapeutic drugs carboplatin, cisplatin, oxaliplatin, carmustine, gemcitabine and etoposide in human lymphoma cell culture. METHODS: RAJI human lymphoma cells were incubated with cytostatics at 37 °C or 42 °C and evaluated for cell culture growth. RESULTS: The number of viable cells after incubation with the drugs (except for gemcitabine) at 42 °C for 30 min was significantly lower than at 37 °C. There were synergism of cytostatic effects of platinum drugs (carboplatin, cisplatin and oxaliplatin) with cytostatic effect of 42 °C and the summation of cytostatic effect of carmustine or etoposide with the action of hyperthermia. The thermal enhancement ratio was 3.0 for oxaliplatin, 2.0 for cisplatin, 1.8-2.4 for carboplatin. The combination of platinum drugs with gemcitabine resulted in a significant enhancement of cytostatic activity. CONCLUSION: Our findings suggest that a gain in sensitivity of RAJI human lymphoma cells to platinum drugs occurs at 42 °C.

Dose enhancement effect of anticaner drugs associated with increased temperature in vitro.

AIM: To evaluate in vitro the influence of elevated temperature (42 degrees C for 60 min) on the action of anticancer drugs doxorubicin, vinorelbine, carboplatin, ifosfamide, etoposide, oxaliplatin, docetaxel and gemcitabine. METHODS: HeLa tumor cell cultures, 24h after seeding, were incubated for 60 min with different concentrations of chemotherapeutical drugs at a temperature of 37 degrees C or 42 degrees C. 48 h later the number of viable cells in the flasks were counted using trypan-blue exclusion on a hemacytometer. RESULTS: Hyperthermia alone caused only 10-20% growth inhibition of cell culture. All the chemotherapeutic drugs used demonstrated a dose enhancement effect at elevated temperature. Thermal enhancement ratio for cell proliferation for oxaliplatin, vinorelbine, carboplatin and ifosfamide exceeded 4, for doxorubicin and gemcitabine exceeded 2. Thermal enhancement ratio for cell death did not exceed 1.4. CONCLUSION: Synergism of hyperthermia and chemotherapeutical drugs was clearly demonstrated for oxaliplatin, vinorelbine, carboplatin, ifosfamide and to a lesser extent for doxorubicin and gemcitabine. Enhancement of the cytostatic effect of anticancer drugs by hyperthermia was more prominent than their cytotoxic effect.

The effect of hypoxia on photocytotoxicity of TICS tricarbocyanine dye in vitro.

AIM: To evaluate the effect of cell oxygenation on photocytotoxicity of a novel tricarbocyanine indolenine dye covalently bound to glucose (TICS). METHODS: HeLa cells were incubated with 5 microM TICS, 2 h later irradiated by laser at 740 nm with a light dose of 10 J/cm(2), delivered at a power density of 10, 20, 25 or 30 mW/cm(2), in air or in argon atmosphere, and then scored for viability. RESULTS: The photocytotoxicity of TICS increased dramatically as the power density was reduced. Under hypoxia TICS-photosensitized cell death was determined but its value was lowered, compared to photoirradiation in the air. CONCLUSION: Photosensitizing effect of TICS is only partially dependent on the oxygenation of tumor cells.

Photodynamic efficacy of topical application of chlorin e6--polyvinyl pyrrolidone complex in tumor-bearing rats.

AIM: To evaluate the antitumor efficacy of photodynamic therapy with ointment form of chlorin e6--polyvinyl pyrrolidone complex. METHODS: 2 or 5% chlorin e6 ointment was applied on the surface of rat SM-1 tumor for 15 min-5 h, and then tumors were scored for photosensitizer accumulation and tissue damage induced by laser irradiation. RESULTS: Selectivity of chlorin e6 accumulation in tumor tissues considerably increases when photosensitizer was applied topically compared with intravenous administration. Antitumor efficacy of photodynamic therapy using topical application of chlorin e6--polyvinyl pyrrolidone complex is just as high as upon intravenous administration of the preparation. CONCLUSION: The level of tissue accumulation of chlorin e6--polyvinyl pyrrolidone complex administered in ointment form allows to carry out fluorescence diagnosis and PDT of superficially localized malignant tumors.

[Cardiological aspects of the antiphospholipid syndrome. Part I. Valvular lesions in the primary and secondary antiphospholipid syndrome and systemic lupus erythematosus]. / Kardiologicheskie aspekty antifosfolipidnogo sindroma. Chast' I. Klapannye porazheniia serdtsa pri pervichnom i vtorichnom antifosfolipidnom sindrome i sistemnoi krasnoi volchanke.

AIM: To assess prevalence of cardiac valvular lesions in patients with primary (P) antiphospholipid syndrome (APLS) and systemic lupus erythematosus (SLE) with and without secondary APLS. MATERIAL AND METHODS: Patients with PAPLS (n=56, 15 men and 41 women), SLE and APLS (n=88, 23 men, 65 women) and SLE without APLS (n=51, 19 men, 32 women) were followed up for 9 years. Serological markers of APLS were anticardiolipin antibodies and lupus anticoagulant. RESULTS: Prevalence of various heart defects was the highest in PAPLS (43%) compared with SLE with APLS (c2=5.6, p=0.001) and SLE without APLS (c2=9.3, p=0.0002). In secondary APLS prevalence of valvular involvement was 27% what was substantially more than in SLE without APLS (4%) (c2=7.2, p=0.0007). Changes of mitral valve cusps and mitral regurgitation were found in 33, 41 and 50% of patients with SLE, SLE with APLS and PAPLS, respectively. Pronounced mitral regurgitation and valve defects were significantly more frequent in patients with any APLS compared with those with SLE without APLS. Thickening of aortic cusps was significantly more frequent in patients with PAPLS compared with patients with SLE (with and without APLS). Changes of tricuspid valve were significantly more frequent in patients with any APLS. Progression of valvular pathology was observed in 2 patients with SLE and APLS after 4 and 5 years of follow up. During 9 years thrombotic complications developed in 8 patients with APLS and valvular lesions (6 strokes, 2 retinal thromboses). CONCLUSION: An association exists between presence of APLS and various cardiac valvular lesions. Lesions of aortic valve are associated with PAPLS: Development of valvular pathology in patients with SLE and PAPLS during follow up dictates the necessity to monitor echocardiographical parameters and titers of anticardiolipin antibodies.