[Liposome formulations of combretastatin A4 and 4-arylcoumarin analog prodrugs: antitumor effect in the mouse model of breast cancer].

The antimitotic agent combretastatin A4 (CA-4) has been suggested as an antivascular agent for anticancer therapy relatively recently. To reduce systemic toxicity by means of administration in liposome formulations, in this study new lipophilic prodrugs, oleic derivatives of CA-4 and its 4-arylcoumarin analog (CA4-Ole and ArC-Ole, respectively), have been synthesized: Liposomes of 100 nm mean diameter prepared on the basis of egg phosphatidylcholine and phosphatidylinositol from bakers yeast have been shown to include completely up to 10 mol. % of CA4-Ole, or 7 mol. % of ArC-Ole. Also, prodrug bearing liposomes decorated with tetrasaccharide selectin ligand Sialyl Lewis X (SiaLe(x)) have been constructed to achieve targeting to endothelium under neovascularization. The antitumor activity in vivo was studied in the model of slowly growing mouse breast cancer. Under the used dose (22 mg/kg) as well as the regimen of treatment (four injections, one per a week, starting from the appearance of palpable tumors) cytostatic CA-4 did not reveal any anticancer effect, and oppositely even stimulated tumor growth. Liposome formulations of CA4-Ole did not show such stimulation. However, to achieve pronounced antitumor effect, number of injections of liposomes should be apparently elevated. New antimitotic agent ArC revealed cytotoxic activity of only one tenth value obtained for CA-4 in vitro in the culture of human breast carcinoma cells. Nevertheless, in vivo in the mouse model of breast cancer this compound showed antitumor effect under double CA-4 equivalent dose. The results demonstrate availability of SiaLe(x)-liposomes loaded with ArC-Ole: this preparation began to inhibit tumor growth already after the second injection. It is necessary further to choose doses and regimens of administration both for ArC and liposome formulations bearing ArC-Ole.

[Estimation of cardiac output from dynamic contrast multispiral tomographic data].

OBJECTIVE: To describe and apply a method for programmatically calculating central hemodynamic parameters from the data of dynamic contrast X-ray computed tomography (CT). MATERIAL AND METHODS: A procedure is proposed to calculate cardiac output (CO) on the basis of the tracer dilution method as a ratio of the injected dose of a contrast agent (Urografin, Shering AG, Austria) to the area under the concentration-time curve derived for one of the cardiac chambers: [see text]. The blood concentration of the agent was estimated from the blood iodine (I) concentration-X-ray density (XD) regression dependence: [XD] = 0.49+22.07 x [I]. Thirty-three patients were studied on a multispiral X-ray Somatom Sensation 4 computed tomograph (Siemens), by injecting 15-20 ml of Urografin. The calculating method was realized as a software package for processing dynamic contrast CT data. RESULTS: The proposed method could exactly determine the values of cardiac output: the correlation with the results of the reference technique (Doppler echo measurement) was highly significant (r = 0.95; p < 0.001) in the whole range of values. Moreover, the data on XD could accurately determine the blood concentration of both iodine (I): [XD] = 0.49+22.07 x [I] and gadolinium as a component of the contrast paramagnetic Gd-DTPA for which the solution concentration-XR dependence was as follows: XD 1.2+33.6 x [Gd]. CONCLUSIONS: Thus, dynamic spiral CT may be also used for the estimation of cardiac output by the tracer dilution method.

[Microbial degradation of components of waste water from phenol-producing industry]. / Mikrobnaia degradatsiia komponentov stochnykh vod proizvodstva fenola.

Processes of aerobic biodegradation of components of phenol production sewage (phenol, acetophenone, dimethylphenylcarbinol, cumene hydroperoxide, alpha-methylstyrene, benzoate, and p-hydroxybenzoate) by bacterial strains obtained from the collection of Saratov Institute of Biocatalysis were studied. The metabolic reactions were shown to be oxidative and have a common catabolic sequence (cumene hydroperoxide-dimethylphenyl-carbinol alpha-methylstyrene-acetophenone-phenyl acetate-phenol-pyrocatechol-aromatic ring breakage). Benzoate and p-hydroxybenzoate were degraded through the formation of pyrocatechol and protocatechuate, respectively. Metabolic pathways were similar in model mixtures of components and sewage samples.

[Storage of industrial microorganisms entrapped into polymer matrices]. / Khranenie promyshlennykh mikroorganizmov, vkliuchennykh v polimernye matritsy.

Our study of the techniques of long-term storage of the biomass of various strains of microorganisms, which cause breakdown or transformation of synthetic organic compounds, demonstrates that desiccated agar beads with immobilized microbial cells can be used for this purpose. In addition, the cells can be stored in desiccated matrices of agar or polyvinyl alcohol, coating synthetic cords. Such dry biocatalysts may be used for quick starting of bioreactors and in other biotechnological processes. The technique is applicable to storage of various strains of Pseudomonas, Corynebacterium, Rhodococcus, and, to a lesser extent, Enterobacteriaceae.

[Protective effects of agar during immobilization of strains capable to degrade aromatic compounds]. / Zashchitnoe deistvie agara pri immobilizatsii shtammov--destruktorov aromaticheskikh soedinenii.

A study of utilization of toxic monoaromatic compounds by microbial cells incorporated into agar matrix revealed positive effects of immobilization on the rate and completeness of biodegradation. This increase in the degrading activity is probably due to a strong protective effect of the polysaccharide carrier. The protective properties of agar are not due to sorptional and diffusional processes in the matrix. These properties were shown to be associated with the formation of a specific extracellular membrane around microcolonies.

[Interrelationship between structural variants of the apolipoprotein B and ischemic heart disease and plasma lipid levels]. / Vzaimosviaz' strukturnykh variantov gena apolipoproteina B s ishemicheskoi bolezn'iu serdtsa i urovnem lipidov plazmy krovi.

Xba I and EcoR I polymorphism of the apolipoprotein B (APOB) gene was studied by PCR. A significant increase in the frequency of allele X+ and haplotype H+E+ was demonstrated in patients with coronarographically documented coronary heart disease (CHD) over that of the general population. Association of allele E- with increased levels of serum triglycerides was found. The results provide evidence about the contribution of structural variants of the APOB gene to determining CHD.

[The use of L-DOPA for treating myocardial infarct patients]. / Primenenie L-DOFA dlia lecheniia bol'nykh infarktom miokarda.

Clinical and experimental studies showed a high therapeutic activity of L-DOPA in combination with traditional methods of infarction treatment. L-DOPA promoted a rapid disappearance of heart failure symptoms and accelerated reparative processes by restoring the activity of the sympathetic nervous system. Correctness of the experimentally developed basically new scheme for administration of neurotropic drugs to patients with infarction depending on the disease stage has been validated.

[Effectiveness of pre-hospital thrombolytic therapy in acute myocardial infarction]. / Effektivnost' tromboliticheskoi terapii ostrogo infarkta miokarda na dogospital'nom étape.

The efficacy and risk of prehospital thrombolysis for acute myocardial infarction (MI) were evaluated in a randomized trial. Patients received streptokinase, 500,000 U, and heparin, 10,000 U, intravenously within 5-10 minutes before (Group 1, n = 50) or after (Group 2, n = 50) hospital admission. One hundred patients took conventional therapy (Group 3). The mean time interval between the onset of symptoms and thrombolytic therapy was 2.2, 4.5, and 3.8 hours in Groups 1, 2, and 3, respectively (p < 0.001). Severe hemorrhages were absent. The rate of ventricular fibrillation was the same in Groups 1 and 3 prior to hospitalization. Left ventricular contractility was identical in Groups 1 and 2. By the end of the fourth week, Group 1 showed a 14% increase in ejection fraction and a 14.5% decrease in akinetic segment, these parameters substantially unchanged in Group 2. The MI size assessed by ECG and the maximum myoglobin concentrations was significantly less in Group 1 than that in Group 2. The patients from Group 1 had fewer MI complications than those from Groups 2 and 3. Three patients died in Group 1, 6 in Group 2, and 16 in Group 3. (p < 0.05).

[Diagnostic usefulness of ECG changes in response to exercise in women with various forms of ischemic heart disease]. / Diagnosticheskaia informativnost' izmenenii nagruzochnoi ekg u zhenshchin c razlichnymi formami ishemicheskoi bolezni serdtsa.

The results of bicycle ergometry and pharmacological tests with isoproterenol and dipyridamol, 24-hour monitoring and blood levels of endogeneous opioids were studied in 99 females with chest pain who had undergone angiography. Coronary microcirculation was examined in 29 patients by introducing albumin microspheres into the left ventricle. The angiography revealed coronary atherosclerosis in 30 patients, whereas its signs were not found in 8 females with documented coronary heart disease (CHD). The predictive value of positive exercise tests in females with angina pectoris was higher for the diagnosis of CHD, including its types without coronary atherosclerosis. In patients with cardialgias, the predictive values of exercise tests were equally low for the diagnosis of coronary atherosclerosis, vasospastic and microvascular CHD types. The patients with cardialgias caused by autonomic dyshormonal myocardiodystrophy showed low blood beta-endorphin and leu-enkephalin levels.

[The choice of the mode of operation of the XeCl-laser for angioplasty]. / Vybor rezhima raboty XeCl-lazera dlia angioplastiki.

The authors relate the results of studies carried out on an outfit model for laser angioplasty designed on the basis of exiplex laser. Optimal conditions for laser introduction into a quartz guide have been found. It is shown that the efficacy of interaction between XeCl-laser and tissue rises as the intensity of radiation increases. The energy of radiation at the guide outlet being 9 mJ, the resources of fiber work remained at a high level (greater than 10(4) impulses) whereas high velocity of tissue evaporation allowed elimination of an area 3 mm3 in volume during 1 minute, with the rate of impulse repetition amounting to 10 Hz.

[Changes in contractile function of the left ventricle under the effect of thrombolytic reperfusion of the coronary arteries in acute myocardial infarct]. / Izmenenie sokratitel'noi funktsii levogo zheludochka pod vliianiem tromboliticheskoi reperfuzii koronarnykh arterii pri ostrom infarkte miokarda.

A total of 73 patients with myocardial infarction (MI) were included into a prospective study involving intravenous and/or intracoronary streptokinase administration. The total ejection fraction (EF) and the extent of left ventricular dys- and akinetic areas were measured by contrast ventriculography in the first 3-9 hours and 4 weeks after the onset of MI symptoms. Coronary reperfusion performed in the first 3 hours after the onset of symptoms in patients with anterior MI (n = 8) and following 3-9 hours (mean 6.6 +/- 0.89 hours) in patients with inferior MI (n = 17) significantly (p less than 0.05) reduced the extent of dys- and akinetic areas from 20.5 +/- 4.16 to 6.0 +/- 3.99 and 10.0 +/- 1.56 to 5.0 +/- 1.74%, respectively) following 4 weeks. EF significantly (p less than 0.01) increased in the former and tended to show an increase from 51.0 +/- 2.44 to 64.0 +/- 2.26% (p less than 0.1) in the latter. In patients with anterior MI (n = 19) there was a tendency to a decrease in the extent of dys- and akinetic areas from 26.0 +/- 2.85 to 17.0 +/- 3.9 (p less than 0.1) following 3-9 hours. No substantial changes were observed in the values of left ventricular dys- and akinesis and EF in patients with anterior (n = 13) and inferior (n = 16) MI without coronary reperfusion.

[Relation between microcirculatory disorders and coronary circulation in patients with a history of myocardial infarction (clinico- angiographic study)]. / Vzaimosviaz' rasstroistv mikrotsirkuliatsii i koronarnogo krovo- obrashcheniia u bol'nykh, perenesshikh infarkt miokarda (kliniko- angiologicheskoe issledovanie).

The interrelationship between bulbar conjunctival microcirculation and coronary blood flow was studied in patients who had sustained myocardial infarction. It was shown that the trends in abnormal changes occurring in the cardiac vessels and their severity might be judged from microcirculatory alterations in the bulbar conjunctiva.

[Clinico-hemodynamic variants of the course of congestive cardiomyopathy]. / Kliniko-gemodinamicheskie varianty techeniia zastoinoi kardiomiopatii.

A total of 45 patients with congestive cardiomyopathy (CCMP) (41 males and 4 females aged 16-57 years) were examined. The study of the clinical picture of the disease has enabled two patient groups to be distinguished: group 1 included 16 patients aged 16-56 years with a rapidly progressive course of the disease and group 2 consisted of 29 patients aged 25-57 years with a slowly progressive form. The symptoms of heart failure were found in all the patients (18 with stage A and 27 with stage B). The cardiothoracal index was 0.64 in rapidly progressive CCMP and 0.58 in slowly progressive one. All the patients with CCMP had a characteristic marked dilatation of all the heart cavities, a sharp decrease in the indices of the pumping and contractile function of the myocardium. These changes were more marked in patients with rapidly progressive CCMP.