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Biomedical subjects

V Pavlov

Publications and source records attributed to V Pavlov.

At least 19 recordsLinked to original sources

Radiation sources based on laser-plasma interactions.

Plasma waves excited by intense laser beams can be harnessed to produce femtosecond duration bunches of electrons with relativistic energies. The very large electrostatic forces of plasma density wakes trailing behind an intense laser pulse provide field potentials capable of accelerating charged particles to high energies over very short distances, as high as 1GeV in a few millimetres. The short length scale of plasma waves provides a means of developing very compact high-energy accelerators, which could form the basis of compact next-generation light sources with unique properties. Tuneable X-ray radiation and particle pulses with durations of the order of or less than 5fs should be possible and would be useful for probing matter on unprecedented time and spatial scales. If developed to fruition this revolutionary technology could reduce the size and cost of light sources by three orders of magnitude and, therefore, provide powerful new tools to a large scientific community. We will discuss how a laser-driven plasma wakefield accelerator can be used to produce radiation with unique characteristics over a very large spectral range.

Journal Article↗

Biofilm development of the polyethylene-degrading bacterium Rhodococcus ruber.

We have recently isolated a biofilm-producing strain (C208) of Rhodococcus ruber that degraded polyethylene at a rate of 0.86% per week (r2=0.98). Strain C208 adheres to polyethylene immediately upon exposure to the polyolefin. This initial biofilm differentiates (in a stepwise process that lasts about 20 h) into cell-aggregation-forming microcolonies. Further organization yields "mushroom-like" three-dimensional structures on the mature biofilm. The ratio between the population densities of the biofilm and the planktonic C208 cells after 10 days of incubation was about 60:1, indicating a high preference for the biofilm mode of growth. Analysis of extracellular polymeric substances (EPS) in the biofilm of C208 revealed that the polysaccharides level was up to 2.5 folds higher than that of the protein. The biofilm showed a high viability even after 60 days of incubation, apparently due to polyethylene biodegradation.

Biodegradation, Environmental↗

Persistence of chromosome aberrations in peripheral lymphocytes from Hodgkin's lymphoma remission patients.

PURPOSE: To analyse spontaneous and in vitro bleomycin-induced chromosome aberrations in peripheral lymphocytes taken from Hodgkin's disease patients after prolonged (up to 31 years) remission periods, and to consider these data from the point of view of the carcinogenic potential of anticancer therapy. MATERIALS AND METHODS: Conventional analysis of chromosome preparations stained with azure-eosin. RESULTS: The mean frequency and patterns of both spontaneous and induced aberrations in remission patients were significantly different from comparison groups (healthy donors and primary Hodgkin's disease patients). Individual values were characterized with high variation and did not show correlation with post-therapy time. New cancer cases diagnosed in remission patients were more frequent in subjects with high chromosome sensitivity to in vitro bleomycin challenge than in patients whose sensitivity to bleomycin was at a control level. CONCLUSIONS: The results are interpreted as suggesting that the tumorigenic potential of radiochemotherapy is mediated via induction of genetic instability in exposed cells. Long after the therapy, the instability may become an initiating event in the development of new malignancies in affected tissues, whereas the instability induced in haemopoietic stem cells may reveal itself in peripheral lymphocytes derived from formerly exposed precursors.

Adult↗

Growth, morphological and biochemical changes in oxa-spermine derivative-treated MCF-7 human breast cancer cells.

The growth inhibitory properties of two oxa-spermine derivatives named compound 1 and compound 2, representatives of a novel type of polyamine derivatives, were studied. Dose-response growth inhibitory curves obtained after 48h drug exposure demonstrated the much higher cytotoxic activity of compound 1 towards MCF-7 human breast cancer cells. Further experiments with compound 1 showed that this oxa-spermine derivative exhibited considerable cytotoxicity with IC(50) values of 3.74 microM and 2.93 microM after 24h and 48h drug exposure respectively. In MCF-7 cells, after 8h drug (10 microM) exposure it caused shrinkage, chromatin condensation and nuclear fragmentation. However, no clear DNA laddering was detected in treated cells. Drug treatment provoked an increase in polyamine oxidase (PAO) activity. This enzyme is able to produce cytotoxic H(2)O(2) and 3-acetamidopropanal, catalyzing the oxidative deamination of N(1)-acetylated derivatives of spermine and spermidine to spermidine and putrescine respectively. Taken together these data demonstrate that the novel oxa-polyamine derivative compound 1 has considerable cytotoxic activity towards MCF-7 cells and indicate that an induction of PAO may be involved in its cytotoxic and apoptotic effects.

Antineoplastic Agents↗

Biochemical effects and growth inhibition in MCF-7 cells caused by novel sulphonamido oxa-polyamine derivatives.

The novel polyamine derivatives sulphonamido oxa-spermine (oxa-Spm) and sulphonamido oxa-spermidine (oxa-Spd) exhibited rapid cytotoxic action towards MCF-7 human breast cancer cells with IC50 values of 4.35 and 6.47 pM, respectively, after 24-h drug exposure. Neither compound is a substrate of serum amine oxidase. Both oxa-Spm and oxa-Spd caused cell shrinkage, as determined by phase-contrast microscopy. After incubation with 10 microM of either compound for 8 h, the cells underwent chromatin condensation and nuclear fragmentation. However, no clear DNA ladder was obtained by electrophoresis. The sulphonamido oxa-polyamine derivatives and especially oxa-Spd enhanced the activity of polyamine oxidase (PAO), an enzyme capable of oxidising N1-acetylated spermine and spermidine to spermidine and putrescine, respectively, generating cytotoxic H2O2 and 3-acetamidopropanal as by-products. The intracellular polyamine content was only marginally reduced in response to drug treatment. In conclusion, our data show that these novel sulphonamido oxa-polyamine derivatives possess high cytotoxic activity against MCF-7 cells and indicate that induction of PAO may mediate their cytotoxicity via apoptosis.

Amine Oxidase (Copper-Containing)↗

Cytotoxicity, DNA binding and localisation of novel bis-naphthalimidopropyl polyamine derivatives.

Bis-naphthalimidopropyl spermidine (BNIPSpd), spermine (BNIPSpm) and oxa-spermine (BNIPOSpm) showed high in vitro cytotoxicity against human breast cancer MCF-7 cells with IC(50) values of 1.38, 2.91 and 8.45 microM, respectively. These compounds were found to effectively displace the intercalating agent ethidium bromide bound to the calf thymus DNA using fluorimetric methods (C(50) 0.08-0.12 microM) and their apparent equilibrium binding constants (K(app)) were calculated to be in the range of 10.5-18 x 10(7) M(-1). Furthermore, strong stabilisation of calf thymus DNA duplex in the presence of bis-naphthalimidopropyl polyamine derivatives (BNIPSpd, BNIPSpm and BNIPOSpm) was observed by UV spectrophotometric analysis (T(m)=93.3-97 degrees C compared with 75 degrees C for calf thymus DNA without drug). Because of their inherent fluorescence, these compounds were localised preferentially inside the nucleus as evidenced by their direct observation under the fluorescence microscope. The results obtained suggest that the cytotoxic activity of the bis-naphthalimidopropyl polyamines may be in part, caused by their effects on DNA.

Breast Neoplasms↗

Androgenic sensitivity of polyamine-oxidizing enzyme activities in female rat tissues.

Effects of testosterone (10 micrograms/100g body weight) on polyamine-oxidizing enzyme activities in female rat uterus, liver and kidney were demonstrated. Testosterone-treated rats exhibited 2.07 fold (p < 0.002) higher uterine polyamine oxidase (PAO) activity and 1.93 fold (p < 0.02) higher diamine oxidase (DAO) activity, as compared to the controls. In the liver, testosterone caused an elevation in PAO (1.39 fold, p < 0.05), but not in DAO activity, whereas in kidney the hormone stimulated DAO (1.30 fold, p < 0.05), but not PAO activity. The effects observed suggest a possible role for testosterone in the modulation of polyamine levels in the female organs studied and especially in uterus.

Amine Oxidase (Copper-Containing)↗

Developmental aspects of polyamine-oxidizing enzyme activities in the mouse kidney. Effects of testosterone.

In the present study developmental patterns of renal polyamine-oxidizing enzymes polyamine oxidase (PAO) and diamine oxidase (DAO) in male and female ICR mice were demonstrated. The effects of testosterone (10 micrograms/100g body weight) on renal PAO and DAO activities were also studied. The differences between sexes in both PAO and DAO activities were most clearly expressed in the immature kidney. At the age of 20 days PAO and DAO activities were 1.52 fold (p < 0.01) and 1.75 (p < 0.02) respectively higher in male mouse kidney than in female. Maturational processes reflected in significant increases in polyamine-oxidizing enzyme activities mainly in female mouse kidney, comparable with the gain in the kidney wet weight. Our data show that testosterone is able to influence renal PAO and DAO activities in addition to the well-known stimulation of polyamine biosynthesis. The hormonal effects were sex and age dependent. The influence of testosterone on renal PAO activity was mainly age dependent. The slight stimulation of renal PAO activity observed in 20- and 50-day old mice, 24 h after testosterone administration, change with a decrease in the enzyme activity at the age of 70 days. The effects of testosterone on renal DAO activity were mainly sex dependent. Testosterone caused stimulation of DAO activity with a very close magnitude (nearly twice) in female mouse kidney, independently of the age of mice. In contrast, in male mice the hormone treatment resulted in a statistically significant increase in renal DAO activity at the age of 70 days (1.3 fold, p < 0.05) only. It could be suggested that our data indicate the different contribution of renal PAO and DAO in androgen regulation of polyamine levels, depending on sex and the stage of the postnatal development.

Amine Oxidase (Copper-Containing)↗

Effects of female sex hormones on polyamine-oxidizing enzyme activities and polyamine concentrations in immature rat uterus and liver.

17 beta-estradiol (E2) and progesterone (P) treatment of immature female rats (10 micrograms/100 g body weight) respectively resulted in 1.38-fold (p < 0.02) and 1.42-fold (p < 0.02) increase in the uterine polyamine oxidase activity, and 2.45-fold (p < 0.001) and 1.43-fold (p < 0.02) increase in the uterine diamine oxidase activity, as compared to the controls. E2 caused a 5-fold (p < 0.05) and a 1.36-fold (p < 0.05) increase in putrescine and spermidine concentration respectively in rat uterus. Increases of 1.7-fold (p < 0.02) and 1.6-fold (p < 0.05) in putrescine and spermine concentration were determined in the P-treated uterus, as compared to the controls. The spermidine/spermine ratio, which is regarded as an index of growth rate, was higher in the E2-treated uterus and lower in the P-treated uterus than in the control uterus. No statistically significant hormonal effects were estimated in the immature liver. The data reported suggest the possibility of an involvement of polyamine-oxidizing enzymes in the modulation of polyamine concentrations in rat uterus by the female sex hormones.

Amine Oxidase (Copper-Containing)↗

[The catabolism of polyamines].

The important role of the natural polyamines putrescine, spermidine and spermine in the normal and pathological cell growth is the main reason for the active investigation of their metabolism. The essential catabolic reactions of polyamine interconversion and terminal oxidation as well as data for the catabolic enzymes and the regulatory mechanisms of their activities are reviewed. The importance of catabolic reactions for the maintenance of the optimal polyamine concentrations during the cell growth and differentiation is also presented. The role of the essential catabolic enzymes spermidine/spermine N1-acetyltransferase, polyamine oxidase and diamine oxidase in normal and pathological cell growth is discussed.

Animals↗

Distribution of polyamine oxidase activity in rat tissues and subcellular fractions.

The activity of polyamine oxidase (PAO) in rat tissues, and its subcellular distribution, were assayed using a simple polarographic method. The highest PAO activity was measured in the liver and the lowest in the skeletal muscle. In liver, kidney and uterus the highest specific PAO activity was found in the light mitochondrial fraction. PAO was not found in the microsomal fraction except in the kidney.

Animals↗

Polyamine oxidase activity and concentration of polyamines in tissues and serum of hamsters with transplantational pigmented melanoma IC-Sofia.

The activity of polyamine oxidase (PAO) participating in the intracellular catabolitic interconversion of the polyamines and the total concentration of polyamines in some tissues of hamsters with transplantational pigmented melamoma IC-Sofia were studied. The experiments were carried out on day 0, as well as on the 11th, 15th, 21st and 27th day after the tumor transplantation. The PAO activity and the polyamine concentration were determined in tumor tissue (with the exception of day 0), in the liver, kidneys, lung and serum (without PAO). A gradual decrease of the PAO activity and a marked rise in the total concentration of polyamines were observed in the growing tumor. In the remaining tissues the PAO activity initially rose slightly until the 15th day, then dropped, whereas the polyamine concentration increased all the time. The dynamics of the enzyme activity and the polyamine concentration were most pronounced in the lung. Tumor growth was not accompanied by changes in the polyamine concentration in the serum.

Animals↗

[Results of the long-term observation and treatment of patients with arterial hypertension].

48 patients, 40 men (mean age 57.4 years) and 8 women (mean age 56.7 years) with stable arterial pressure--II B and III stage according to A. L. Miasnikov's classification, were treated and followed up dynamically in the course of 8 years. The treatment with diuretics, beta-blockers and reserpin has led to a permanent and satisfactory regulation of arterial pressure in most of the patients. Only in 10.4% of the patients the therapeutic results were not satisfactory. In spite of the normalization of the arterial pressure the number of patients with various forms of ischemic heart disease is high--79.2%. The risk factors and their combinations play an important role for this condition (diabetes mellitus, gout, obesity, lipid metabolism changes, etc.). These data imply a new assessment of the drugs used in the treatment of arterial hypertension.

Antihypertensive Agents↗

[Cellular and humoral immune responses in calves after experimental infection with bovine herpesvirus 1].

Studied were some of the humoral and cellular factors of immunity with calves experimentally infected with Herpes virus 1. The clinical signs manifested by the infected calves were followed up for 10 to 12 days. The shedding of the virus through the nasal mucosa was demonstrated up to the eighth day, the peak values reached being between the 3rd and 5th day of infection. Demonstrated was blastic transformation in vitro with a phytohemagglutinin of the lymphocytes obtained from the peripheral blood prior to infection; the same phenomenon was observed also with each sample taken from the peripheral blood of the controls. Blastic transformation of lymphocytes was demonstrated also with the use of a specific antigen with the group infected from the 6th to the 15th day, with highest indices between the eighth and tenth day. This spoke of the presence of an immune response. The humoral immune response, followed up in its dynamics, was manifested by the presence of local antibodies in the infected calves first on the eighth day, and of serum antibodies on the 12th day. The results obtained point to the importance of both components of immunity with calves. It is of interest to note that the peak of the cell response set in on the eighth to ninth day of infection which coincided with the cease of virus shedding. On the other hand, the serum antibodies were demonstrated later--between the eighth and the twelfth day. This data showed that cellular immunity played a greater part in the recovery of calves in the case of a primary Herpes virus 1 infection.

Animals↗

[Immune response of calves following vaccination with Paramyxovirus parainfluenzae-3 and adenovirus-1 under different colostral immunity stresses].

Studied was the immune response of calves, with colostrum antibodies and without colostrum antibodies, immunised with different dosages of live bivalent vaccine against P. parainfluenzae-3 and Adenovirus-1. For the group of calves with colostrum immunity, after single hypodermic immunisation with doses from 10(4) till 10(5) CPE50/cm3 for adenovirus, was not proved immune response, as a result of blocking of the vaccinal antigen of colostrum antibodies. For calves which missed these antibodies, the immune response was determined at the 15th day after the first vaccination with the lesser dose of bivaccine. Regardless of the degree of the antibodies of the calves, after the second vaccination (with the big and the little dose) was proved immune response, which does not differ considerably for the separated groups of calves. It was established, that the optimal dose, necessary for the calves to build an immunity at an early age (from 1 to 3 months), when immunised with bivaccine, was 10(4) CPE50/cm3 for the P. parainfluenzae-3 and 10(3) CPE50/cm3 for the Adenovirus-1. The bigger dose is useless not only from the economic point of view, but from the danger of provoking an unwanted shock of the vaccinated calves.

Adenoviridae↗

Changes in the conductivity and in the functional refractory period of the atrioventricular node during hypoxia.

The experiments were carried out on preparations from rabbit right atrium, containing the sinoatrial node, the interatrial barrier, the atrioventricular node and the His-bundle. Surface electrodes were used to record the atrial and His-electrograms. The conduction time (AH-interval) was measured and the functional refractory period of the node was determined during normoxia (95% O2, 5% CO2) and hypoxia (30% O2, 65% N2 and 5% CO2) for 45 min. Hypoxia causes a considerable delay in conduction. This delay is greater for the shorter coupling-intervals and at the higher frequencies of the imposed rhythm. The shifting of the conduction times towards the higher values during hypoxia is not parallel compared with hypoxia. In the case of hypoxia the refractory curve of the A-V node is situated higher than the curve during normoxia, owing to the greater duration of the H1H2 intervals. The functional refractory period is increased and shifted toward the longer coupling-intervals. The results obtained show that during hypoxia the functional refractory properties of the atrioventricular node are impaired, which, combined with the delayed conduction through it, creates conditions for serious disturbances in the function of the atrioventricular conduction system.

Animals↗

Inert characteristic and functional refractory period of the atrioventricular node in rabbit heart preparation.

The effect of heart rate on the functional refractory period (FRP) of the atrioventricular node (AVN) is studied. A conclusion is reached that FRP, being a complex characteristic of AVN, should not be directly related to conduction time, but it can serve as a measure of the maximum moment acceleration which AVN is capable of transmitting to the lower-lying structures. It is proposed to use the coefficient of relative acceleration for quantitative estimation of the inert (dynamic) properties of the node at different heart rates. It is concluded that for a longer basic cycle length (BCL) AVN is characterized by greater reserve possibilities for transformation of accelerations of the input rhythm.

Animals↗