Investigation of the mutagenic and antimutagenic effects of Origanum compactum essential oil and some of its constituents

In the present study, the chemical composition of Origanum compactum essential oil was determined by gas chromatography and mass spectrometry, and its mutagenic and antimutagenic activities were investigated by the somatic mutation and recombination test (SMART) in Drosophila melanogaster. No significant increase in the number of somatic mutations was observed with the essential oil tested using both the standard (ST) and high bio-activation (HB) cross. In order to investigate the antimutagenic effect of the essential oil, we have tested the effect on the indirect-acting mutagen urethane (URE), as well as the direct-acting mutagen methyl methanesulfonate (MMS). O. compactum essential oil showed a strong inhibitory effect against URE-induced mutagenicity, especially with the HB cross. However, only a weak inhibitory effect on the mutagenicity induced by MMS was observed. These results suggest that the detected antimutagenicity could be mediated by an inhibitory effect on metabolic activation. The essential oil was fractionated to identify the components responsible of the suppressing effect detected. Seven fractions were obtained: two of them showed the most potent inhibitory effect against URE-induced mutagenicity and were further fractionated. The sub-fractions obtained from the second chromatographic fractionation were tested for their antimutagenic activity, together with carvacrol and thymol. The highest antimutagenic effect obtained with the sub-fractions was similar to the effect of the crude essential oil, as well as to the effect of carvacrol alone. These results suggest the absence of a synergic antimutagenic effect between the components of O. compactum essential oil and indicate that carvacrol was the most active oil component.     

Synthesis and evaluation of water-soluble resveratrol and piceatannol via BGLation

Synthesis of four water-soluble resveratrol and piceatannol derivatives bearing symmetrically branched glyceryl trimer (BGL003) with a non-biocleavable linkage, and their biological evaluation as a mitochondrial fusion-inducing agent with cellular fat-reducing effect from cells, is described. The effect of Piceatannol-BGL003 conjugate was as high as that of original stilbenoids.     

Prenatal Effect of Fluoxetine on Nociceptive System Reactivity and Psychoemotional Behavior of Young Female and Male Rats

Reactivity of the nociceptive system, psychoemotional behavior and cognitive abilities in female and male rats born to mothers that were exposed to chronic injection of fluoxetine, a serotonin reuptake inhibitor, on days 9–20 of pregnancy were studied in a battery of behavioral tests during the prepubertal period. It was found that chronic injection of physiological saline to pregnant females evoked enhanced nociceptive responses in their offspring of both sexes while fluoxetine injection neutralized the effects of such an invasive intervention, demonstrating thereby the antinociceptive effect of this agent. Negative effects of maternal fluoxetine included a weight loss in the neonate offspring of both sexes and 25-day-old males, as well as the increased anxiety level in females only as detected in the elevated plus maze test. Fluoxetine had no effect on the level of depressive-like behavior in the forced swim test in rats of both sexes. The positive prenatal effect of fluoxetine manifested itself in males as an improved spatial learning ability in the Morris water maze; the anti-nociceptive effect of chronic fluoxetine injection, as compared to the pro-nociceptive effect of chronic saline injection, can also be considered as a positive effect of fluoxetine. Sex differences in the prenatal effect of fluoxetine were revealed in the anxiety level with more anxiety behavior in females.     

Propagule interactions and the evolution of virulence

The evolution of parasite virulence is thought to involve a trade‐off between parasite reproductive rate and the effect of increasing the number of propagules on host survivorship. Such a trade‐off should lead to selection for an intermediate level of within‐host reproduction (λ). Here I consider the effects of parasite propagule number on selection affecting λ when (i) the effect of each propagule is independent of propagule number, and (ii) when the effect of each propagule changes as a function of propagule number. Virulence evolves in these models as a correlated response to selection on λ. If each propagule has the same effect (s) as all previous propagules, the survivorship of infected hosts is reduced by more than 60% at equilibrium, independent of the value of s. If, instead, each propagule has a more negative effect on host survivorship than previous propagules, host survivorship at equilibrium is expected to increase as the effect becomes more pronounced. These results are directly parallel to results derived for population mean fitness at mutation‐selection balance; and they suggest that high virulence should be associated with parasites for which the effect of adding propagules either remains constant or diminishes with propagule number.     

Potentiation of Inhibitory Activity of Colistin on Pseudomonas aeruginosa by Sulphamethoxazole and Sulphamethizole

Potentiation of colistin by sulphamethoxazole and sulphamethizole was demonstrated with 19 out of 20 strains of Pseudomonas aeruginosa. This enhancement was bactericidal as well as bacteriostatic. Synergy between trimethoprim and sulphamethoxazole was also demonstrated with four strains of Ps. aeruginosa, but even when the two drugs were combined high concentrations of trimethoprim were still required to produce a bactericidal effect. Combinations of sulphamethoxazole and gentamicin appeared to be synergistic when the bacteriostatic effect was measured, but the combined bactericidal effect was indifference. The bactericidal and bacteriostatic effect of combinations of carbenicillin with sulphamethoxazole was also indifference.     

Experimental study of the effects of amiridin and tacrine on learning and memory

The authors studied the influence of amiridin and tacrine on learning and memory in mice and rat by passive avoidance conditioning test at norm and under scopolamine induced amnesia as well as of their effect on acetylcholine esterase (AChE) activity in brain cortex homogenates. Amiridin in doses 0.1 and 0.2 mg/kg showed a beneficial action on conditioning in untreated animals, its effect being comparable with that of piracetam. Tacrine was ineffective. In scopolamine treated animals amiridin and tacrine showed anti-amnestic action at dose of 0.1 mg/kg which was found ineffective with respect to AChE activity. The data suggests that the ameliorating effect of amiridin and tacrine on cognitive abilities in patients with senile dementia is not related their anticholinesterase properties.     

Effect of dehydroepiandrosterone and its sulfate and fatty acid ester derivatives on rat brain membranes

The effects of dehydroepiandrosterone (DHEA) as well as its sulfate and fatty acid ester derivatives on rat brain membrane fluidity was investigated by fluorescence depolarization of a lipid probe 1,6-diphenyl-1,3,5-hexatriene and compared to its effect on phospholipid conformation investigated by Fourier transform infrared spectroscopy. In rat brain, membrane fluidity varied rostro-caudally, the frontal cortex showing the highest fluidity compared to the hypothalamus, hippocampus, striatum, thalamus, and hindbrain. As previously reported, it was observed that cholesteryl hemisuccinate and stearic acid rigidify striatal membrane whereas linoleic acid and L-alpha-phosphatidylcholine increase the membrane fluidity. Striatal fluidity was increased in vitro with increasing concentrations of DHEA, this effect was greater with the DHEA fatty acid ester derivatives (DHEA-L), DHEA-undecanoate, and DHEA-stearate, whereas no effect was observed with DHEA-sulfate (DHEA-S). In the frontal cortex only the two DHEA-L derivatives increased membrane fluidity, whereas DHEA and DHEA-S were without effect. The effect of DHEA-L on synthetic dimyristoylphosphatidylcholine-d54 phospholipid membranes indicates a disordering effect of DHEA-undecanoate and DHEA-stearate as reflected by increased trans-gauche isomerization of the acyl chains of the lipid. Hence, DHEA-L increase the disorder and/or fluidity of brain membranes; interestingly, these compounds are abundant in the brain where they are generally considered as storage compounds that slowly release the active unconjugated steroid hormone.     

The structure, growth and formation of bones in toxic exposure of the body to pesticides and antioxidant therapy]

In the experiment performed on 175 white male rats by means of a complex of morphological, biochemical and biomechanical methods peculiarities of structure, growth, outline formation and mineralization of the skeletal bones have been investigated under a toxic lesion of the organism with pesticides (chlorophose and keltan) and at a simultaneous administration of antioxidants of various groups (tocopherol, ionol, sodium selenit). Osteotoxic effect of the pesticides, manifested as an inhibition of bone growth, as a disbalance of mineral saturation and their composition, as a decrease in indices of firmness is leveled by means of therapeutic doses of the antioxidants. The stabilizing effect of the antioxidant applied correlates to the manifestation of the pesticides osteotoxic effect, to the ability of their cumulation in the organism and is directly connected with the supposed mechanism of damaging effect to the organism and/or cell. The expressiveness of the toxic effect of the chemical poison, in its turn, is defined not only by the dose, mechanism and duration of the effect, but by age peculiarities of the organism and by functional state of its reactivity. When the poisons are applied for a long time, in order to level their osteotoxic effect, a multiple increase of therapeutic doses of the antioxidants and a combined potentiation of their effect are necessary.     

Bactericidal effects of ampicillin and streptomycin on intracellular and extracellularYersinia pseudotuberculosis

The bactericidal effect of ampicillin and streptomycin on intracellularYersinia pseudotuberculosis was studied using infected HeLa cells as a model system. The results were compared with the effect of the antibiotics on extracellular bacteria in order to evaluate the protective effect of intracellular residence. Ampicillin and streptomycin could be shown to be effective against intracellular bacteria, but had a more pronounced effect on extracellular bacteria. The bactericidal effect of ampicillin and streptomycin at different concentrations follows a commonly accepted formula concerning the relationship between concentration of disinfectant and time of disinfection.     

Hormonal disturbances and effect of pharmaca.

The hormonal milieu of the organism may exert certain influences on the activity and lasting of the effect of some drugs. This was demonstrated in female rats with the example of a steroid hormone (estrone) and a short acting barbiturate derivative (hexobarbital). Estrus produced with estrone is not to be influenced by ovariectomy. Hyperthyrosis lead to the cumulation of estrogens in active form and lengthened their effect. Hypothyrosis accelerated estrogen metabolism inducing a relatively ephemer effect of estrone. Hexobarbital metabolism is faster in ovariectomised rats as well as in thyroidectomised ones than in controls. The catatoxic effect of testosterone is bringing about a short anesthesia. Hyperthyrosis reduced the effect of hexobarbital to one fourth of the control values. A special care is necessary in administering drugs when endocrine disorders are present. Individual dosages of the pharmaca may be taken into consideration to adapt the right dosages to the hormonal disturbances.     

Genotoxicity of idarubicin and its modulation by vitamins C and E and amifostine

Idarubicin is an anthracycline anticancer drug used in haematological malignancies. The main side effect of idarubicin is free-radicals based cardiotoxicity. Using the comet assay we showed that the drug at concentrations from the range 0.001 to 10 microM induced DNA damage in normal human lymphocytes, measured as the increase in percentage of DNA in the tail (% tail DNA). The effect was dose-dependent. Treated cells were able to recover within a 120-min incubation. Recognised cell protector, amifostine at 14 mM decreased the mean % tail DNA of the cells exposed to idarubicin at all tested concentrations of the drug. So did vitamin C at 10 microM, but vitamin E (alpha-tocopherol) at 50 microM increased the % tail DNA. Lymphocytes exposed to idarubicin and treated with endonuclease III, formamidopyrimidine-DNA glycosylase and 3-methyladenine-DNA glycosylase II, enzymes recognizing oxidized and alkylated bases, displayed greater extent of DNA damage than those not treated with these enzymes. Pretreatment of lymphocytes with nitrone spin traps, N-tert-butyl-alpha-phenylnitrone and alpha-(4-pyridil-1-oxide)-N-tert-butylnitrone decreased the extent of DNA damage evoked by idarubicin. To discuss the influence of vitamins and amifostine in cancer cells we used also murine pro-B lymphoid BaF3 transformed with BCR/ABL oncogene. These cells can be treated as model cells of human acute myelogenous leukemia. The response of these cells to vitamin E was quantitatively the same as human lymphocytes. However, vitamin C did not exert any effect on DNA damage and amifostine, in spite to normal lymphocytes, potentiated this effect. The results obtained suggest that reactive oxygen species, including free radicals, may be involved in the formation of DNA lesions induced by idarubicin. The drug can also methylate DNA bases. Our results indicate that not only cardiotoxicity but also genotoxicity and in consequence induction of secondary malignancies should be taken into account as diverse side effects of idarubicin. Amifostine may potentate DNA-damage effect of idarubicin in cancer cells and decrease this effect in normal cells. Vitamin C can be considered as protective agents against DNA damage in normal cells in persons receiving idarubicin-based chemotherapy, but the use of vitamin E cannot be recommended and at least needs further research.     

Inference of haplotype effects in case-control studies using unphased genotype and environmental data

A retrospective likelihood-based approach was proposed to test and estimate the effect of haplotype on disease risk using unphased genotype data with adjustment for environmental covariates. The proposed method was also extended to handle the data in which the haplotype and environmental covariates are not independent. Likelihood ratio tests were constructed to test the effects of haplotype and gene-environment interaction. The model parameters such as haplotype effect size was estimated using an Expectation Conditional-Maximization (ECM) algorithm developed by Meng and Rubin (1993). Model-based variance estimates were derived using the observed information matrix. Simulation studies were conducted for three different genetic effect models, including dominant effect, recessive effect, and additive effect. The results showed that the proposed method generated unbiased parameter estimates, proper type I error, and true beta coverage probabilities. The model performed well with small or large sample sizes, as well as short or long haplotypes.     

Influence of glucose on the kinetics of maltodextrin hydrolysis using free and immobilized glucoamylase

The study of the effect of glucose addition to the kinetics of maltodextrin hydrolysis catalyzed with free and immobilized Aspergillus niger glucoamylase does not show any significant glucose inhibitory effect. This result is in contradiction with data previously reported in the literature. On the contrary, a slight glucose-activating effect was observed. This effect was greater in the case of the immobilized enzyme. The glucose inhibitory effect may thus not be involved in the case of practical saccharification conditions catalyzed with glucoamylase when maltodextrins are used as substrate.     

Adaptation of electropic and ionotropic vagal effects on the isolated rabbit atrium]

Long-time vagal stimulation induces a decrease of electrotropic and inotropic effects on the isolated rabbit atrium in spite of constant stimulation frequency. This decrease is defined as effect adaptation. To compensate this effect adaptation, the n. vagus was stimulated with increasing stimulation frequency. Compensation is possible for a certain period referred to as control time. The adaptation of the electrotropic effects is more delayed and weaker than the inotropic effect adaptation. The control times of the electrotropic effect are longer than those of the inotropic effect. Acetylcholine perfusion without vagal stimulation shows the same results. It was shown that the effect adaptaion does not result from depletion of acetylcholine stores or from co-stimulation of sympathetic nerve fibres. The effect adaptation is discussed as being the result of machano-electrical coupling.     

A comparative study of Aldactone and Diane in the treatment of hirsutism

A comparative study has been performed in order to evaluate the relative potency of Diane and Aldactone in reducing hair growth as well as the effect on blood hormone concentrations. Thirty-six women participated in the study and depending on the desire for contraception, 22 were treated with Diane and 14 with Aldactone. The results show that Aldactone (50 mg per day) had little effect on hormone concentrations, only LH was significantly reduced after 12 months of treatment. Despite the lack of effect on hormone levels, all 14 women reported reduced hair growth and after 5 months of treatment, 58% also reported a decrease in the formation in new hair growth. In contrast to the Aldactone treated group, the women on Diane medication demonstrated a marked decrease in circulating hormone levels with a subsequent effect on the hair parameters. The clinical effects were, however, not quite of the same degree as those seen with Aldactone treatment. Approximately 20% exhibited no response for any of the 3 hair-parameters (reduced hair growth, formation of new hair and a change to softer hair). The response time before any effect was observed was also longer than that seen with the Aldactone group. The data suggest that, at the dosages employed, Aldactone has a better clinical effect on the hair parameters despite a lack of effect on circulating hormone levels. One should, however, be aware that Diane contains only 2 mg cyproterone acetate (CPA) and a better effect would most probably have been obtained using a higher dosage of CPA.     

生态边缘效应与生态平衡变化方向

边缘效应作为一个生态现象和生态学概念越来越为更多的人所重视 ,因为它与物种保护、生态环境保护等自然保护和开发利用以及生态恢复、生态建设等人类参与自然活动的关系十分密切 ,并逐渐被人们所认识。1　边缘效应研究现状及重要性　　早在 1 933年 Leopold对森林片段的边缘效应进行了开创性的研究[1] 。1 942年 Beecher便指出 ,在两个或多个不同生物地理群落交界处 ,往往结构复杂 ,出现不同生境的种类共生 ,种群密度变化较大 ,某些物种特别活跃 ,生产力亦相应较高 ,这种现象即边缘效应。随着人们对这一概念的逐渐重视 ,该领域的研究愈加…     

Effect of glutamine on synaptosome respiration of the rat brain in depolarization and sleep disturbance

Depolarization induced by the increase in potassium content in the medium results in the augmented oxygen consumption by the rat brain synaptosomes, when glucose and pyruvate were used as substrates; with glutamate as substrates no such effect of potassium occurred. No effect of depolarization is present in the case of synaptosomes from animals with a paradoxical sleep deprivation; the addition of glutamine (0.5 mM) restores the capability in synaptosomes of metabolic response to depolarization. No effect of glutamine is observed with synaptosomes from brain hemispheres of rats with disturbed sleep.     

Point and interval estimation of baseline risk and treatment effect based on logistic model for observational studies

In observational studies with dichotomous outcome of a population, researchers usually report treatment effect alone, although both baseline risk and treatment effect are needed to evaluate the significance of the treatment effect to the population. In this article, we study point and interval estimates including confidence region of baseline risk and treatment effect based on logistic model, where baseline risk is the risk of outcome of the population under control treatment while treatment effect is measured by the risk difference between outcomes of the population under active versus control treatments. Using approximate normal distribution of the maximum‐likelihood (ML) estimate of the model parameters, we obtain an approximate joint distribution of the ML estimate of the baseline risk and the treatment effect. Using the approximate joint distribution, we obtain point estimate and confidence region of the baseline risk and the treatment effect as well as point estimate and confidence interval of the treatment effect when the ML estimate of the baseline risk falls into specified range. These interval estimates reflect nonnormality of the joint distribution of the ML estimate of the baseline risk and the treatment effect. The method can be easily implemented by using any software that generates normal distribution. The method can also be used to obtain point and interval estimates of baseline risk and any other measure of treatment effect such as risk ratio and the number needed to treat. The method can also be extended from logistic model to other models such as log‐linear model.     

Interaction with Esterases and Mechanism of Synergistic Action of Thio- and Dithiophosphates Containing the Fragments N-Acylated Glycine and β-Alanine

We studied the interaction between O,O-diethyl-S-[(N-acyl-N-alkoxycarbonylalkyl)aminomethyl]thiophosphates and mammalian cholinesterases as well as esterases from insect tissue extracts by kinetic methods and disc electrophoresis. The coefficients of combined effect of these compounds or their dithioanalogs with permethrin were determined. The obtained data suggest that the synergistic effect on the common cockroaches and houseflies is chiefly due to carboxylesterase inhibition by monothioderivatives and monooxygenase suppression by dithioderivatives, respectively.     

Oxygen- and temperature-dependent cytotoxic and radiosensitizing effects of cis-dichlorodiammineplatinum(II) on human NHIK 3025 cells in vitro

The radiosensitizing effect of the chemotherapeutic drug cis-dichlorodiammineplatinum(II) (cis-DDP) was tested on human NHIK 3025 cells cultivated in vitro. cis-DDP was found to exert a radiomodifying effect under hypoxic but not under aerobic conditions. These results confirm that cis-DDP may act as a radiosensitizer of hypoxic cells; however, the radiosensitizing effect was seen only at concentrations of cis-DDP having a considerable cytotoxic activity, and for practical reasons concerning survival level the highest drug concentration that was investigated was 15 microM at 37 degrees C. The radiosensitizing effect was of a dose-modifying type and with a dose-modifying factor (DMF) of 1.2 at 15 microM in hypoxic cells. The radiosensitizing as well as the cytotoxic effect of cis-DDP was found to be strongly temperature dependent. Isoeffect doses of cis-DDP was reduced with a factor of 3 at 22 as compared to 37 degrees C. We also found that hypoxic cells were less sensitive to cis-DDP than cells treated in the presence of oxygen. To test the correlation between cytotoxicity and radiosensitization on the one hand and cellular uptake of cis-DDP on the other, cell-associated Pt was measured by atomic absorption spectroscopy. From these studies the cytotoxicity of cis-DDP at 22 and 37 degrees C under aerobic conditions was found to be the same as long as the amount of cell-associated Pt (i.e., the cellular uptake) was the same. However, whether the cells were treated under hypoxic or aerobic conditions, the cellular uptake of Pt was the same. While the radiosensitizing effect was present at 37 and at 40 degrees C, no such effect could be found at 22 degrees C. Since the cytotoxicity of cis-DDP as well as the drug uptake was reduced about three times at 22 as compared to 37 degrees C, we increased the concentration threefold, to 50 microM at 22 degrees C. Still no radiosensitizing effect was found at this temperature.