RADIATION DAMAGE OF THE NERVOUS SYSTEM AND ENDOCANABINOIDS. / RADIATsIINE URAZhENNIa NERVOVOÏ SYSTEMY I ENDOKANABINOÏDY.

The review analyzes the change of the existing paradigm of high radioresistance of the nervous system according tothe results of the study of neuropsychiatric disorders in in the aftermath of the Chornobyl accident in both earlyand remote post-accident period. The participation of the endocannabinoid system in ensuring homeostasis andpathology formation, potential possibilities of using cannabis drugs, agonists and antagonists of endocannabinoidreceptors for the treatment of early and long-term effects of radiation are considered.

STUDY OF SUICIDE BEHAVIOR IN JOINT FORCE OPERATION VETERANS IN EASTERN UKRAINE AND IN LIQUIDATORS OF THE CONSEQUENCES OF THE CHORNOBYL ACCIDENT. / DOSLIDZhENNIa SUÏTsYDAL'NOÏ POVEDINKY U VETERANIV OPERATsIÏ OB'IeDNANYKh SYL NA SKhODI UKRAÏNY I LIKVIDATORIV NASLIDKIV AVARIÏ NA ChORNOBYL'S'KII ATOMNII ELEKTROSTANTsIÏ.

The article is devoted to the problem of completed suicides among veterans of the Joint Forces for National Securityand Defense operation in Donetsk and Luhansk regions (JFO) and liquidators of the consequences of the Chornobylaccident (LCCA). The results of the analysis of surveys of families and close associates of JFO veterans who committed a completed suicide in the period 2014-2019 are presented. The survey was conducted as part of criminal proceedings initiated on the facts of suicide. OBJECTIVE: to analyze the current dynamics of suicidal behavior in veterans of JFO and the impact of psychosocialfactors on its development and compare with the relevant indicators among LCCA at the Chornobyl nuclear powerplant. MATERIALS AND METHODS: 175 questionnaires are presented, socio-demographic characteristics are compiled and psychosocial factors that influenced the development of suicidal behavior in environmental protection veterans areidentified. An analysis of the status of such studies among liquidators of the Chornobyl accidents. RESULTS: the data analysis of suicidal behavior in veterans of environmental protection, the impact on its development of psychosocial factors and comparison with the indicators among LCCA at the Chornobyl Nuclear PowerPlant. CONCLUSIONS: The results of the study show that in emergency situations, mostly men from all regions of the country, both professional servicemen and civilians, are involved in its elimination. It has been proven that while performing their official duties, the veterans of JFO and LCCA at the Chornobyl nuclear power plant experienced mental stress. But most of them, returning home, did not seek medical treatment, prevent the development of diseasesand their complications and remained for a long time without proper medical, social and psychological care.

[Radical cystectomy: therapeutic aspects of preoperative and early postoperative management].

AIM: to improve the results of radical cystectomy by optimization of patient preparation for surgery and early postoperative care. MATERIALS AND METHODS: A total of 136 patients who underwent radical cystectomy and either orthotopic ileal neobladder or ileal conduit formation were included in the study. Brikkers operation was performed in 92 patients (76% men and 24% women) aged from 39 to 83 years, while in 44 patients (97.7% men, 2.3% women) aged from 32 to 75 years the Studer ileal neobladder was created. All patients underwent preoperative comprehensive examinations in order to determine type and extent of surgical treatment. RESULTS: A complication rate after radical cystectomy with urine derivation using bowel segment was 49.2%. Mortality rate in early postoperative period was 3.9%. CONCLUSION: An algorithm of postoperative care after radical cystectomy with formation of either orthotopic neobladder or ileal conduit and consideration of comorbid status and preparation which we have used in clinical practice was developed. According to the results, after implementation of algorithm of management in preoperative and early postoperative period a decrease in complications and mortality rate has been found.

Laccase isoform diversity in basidiomycete Lentinus strigosus 1566: Potential for phenylpropanoid polymerization.

Three laccase isoforms with different physicochemical properties could be purified from culture liquid of basidiomycete Lentinus strigosus 1566 obtained during submerged cultivation. The purified laccases possessed individual selectivity in relation to different phenolic compounds. Laccases I, II, and III (59, 65, and 61 kDa respectively) were more active in acidic conditions at around 70 °C. However, in contrast to laccases I and II, laccase III retained its activity (8-30%) and stability during at least one week of incubation at neutral conditions that allows its biotechnological application carried out at neutral environment. The activation phenomena for some of the purified laccases from L. strigosus 1566 during incubation at high temperature, different pH, and sulfates is shown and discussed. According to MALDI-TOF analysis, laccases I and II are most closely related to the laccase of Panus rudis (AAR13230). Transformation of phenylpropanoids by the predominant laccases of L. strigosus 1566 to different polymers was demonstrated, indicating a great potential for producing novel pharmaceutical valuable analogues of lignans, stilbenes, flavonoids, and etc.. The studied laccases, which are products of the same strain, can become a convenient model for further studies of the structural mechanisms of the shift of T-/pH-optima, activation, and T-/pH-stability.

The cardiovascular benefits of indiscriminate supplementation of omega-3 fatty acids; meta-analysis and decision-making approach.

AIM: The meta-analysis was conducted to estimate of the cardiovascular benefits of indiscriminate supplementation of omega-3 capsules. The results, expressed in terms of quality adjusted life years (QALY) intuitively understood by the general public, can be the basis for the (personal) decision on whether to take omega-3 supplements. METHODS: The results of meta-analysis of eight double-blind, placebo-controlled clinical trials are expressed in terms of QALY, using the Markov model and Monte Carlo simulations. RESULTS: Omega-3 supplementation results in a 8% decrease of the risk of cardiac death, unless the patients are treated by statins. Results indicate that omega-3 supplementation may prolong QALY by about a month. Old people gain less, whereas DM-2 patients and people with history of CV events gain more. DISCUSSION: Our analysis yielded an algorithm for estimating benefit from omega-3 supplementation, based on the age and the individual risk of CV events of the patient.

[Importance of surgery of quick recovery program for surgical treatment of bladder tumors].

The article presents an analytical review of literature outlining the prospects for the use of the program "Surgery of quick recovery" in the surgical treatment of the bladder malignant tumors. The multi-modal program "Surgery of quick recovery" was found to reduce the number of postoperative complications and shorten recovery of patients with bladder cancer.

G-CSF and G-CSFR are highly expressed in human gastric and colon cancers and promote carcinoma cell proliferation and migration.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) is a pro-inflammatory cytokine that stimulates myeloid stem cell maturation, proliferation, and migration into circulation. Despite being a known growth factor, the impact of G-CSF on solid tumours has not been well examined. G-CSF receptor (G-CSFR) is expressed by some tumours, and thus the aim of this study was to examine the expression and impact of G-CSF and G-CSFR on gastrointestinal tumours. METHODS: In this study, G-CSF expression was examined in human gastric and colon tumours and by tumour-derived stromal myofibroblasts and carcinoma cells. G-CSFR expression was examined on carcinoma cells isolated from human tissues. The effects of G-CSF on gastric and colon carcinoma cell proliferation, migration, and signalling were examined. RESULTS: G-CSFR was highly expressed in 90% of human gastric and colon carcinomas. G-CSF was also found to be highly produced by stromal myofibroblasts and carcinoma cells. Exposure of carcinoma cells to G-CSF led to increased proliferation and migration, and expansion of a sub-population of carcinoma cells expressing stem-like markers. These processes were dependent on ERK1/2 and RSK1 phosphorylation. CONCLUSIONS: These data suggest that the G-CSF/R axis promotes gastric and colorectal cancer development and suggest they are potential tumour targets.

Evaluation of antioxidants: scope, limitations and relevance of assays.

Peroxidation of lipids, particularly polyunsaturated fatty acid residues (PUFA) of phospholipids and cholesterol esters, is a process of marked implications: it shortens the shelf-life of food and drugs, it causes fragmentation of DNA, it damages cellular membranes and it promotes the genesis of many human diseases. Much effort is therefore devoted to a search for "potent antioxidants", both synthetic and from natural sources, mostly plants. This, in turn, requires a reliable, simple, preferably high throughput assay of the activity of alleged antioxidants. The most commonly used assays are based on measurements of the total antioxidant capacity (TAC) of a solution, as evaluated either by determining the rate of oxidation of the antioxidant or by measuring the protection of an easily determined indicator against oxidation by the antioxidants. The commonly used assays utilized for ranking antioxidants share three common problems: (i) They usually evaluate the effects of those antioxidants that quench free radicals, which constitute only a part of the body's antioxidative network, in which enzymes play the central role. (ii) Both the capacity and potency of antioxidants, as obtained by various methods, do not necessarily correlate with each other. (iii) Most estimates are based on methods conducted in solution and are therefore not necessarily relevant to processes that occur at the lipid-water interfaces in both membranes and micro emulsions (e.g. lipoproteins). Given this "state of art", many researchers, including us, try to develop a method based on the formation of hydroperoxides (LOOH) upon peroxidation of PUFA in lipoproteins or in model membranes, such as liposomes. In these systems, as well as in lipoproteins, the most apparent effect of antioxidants is prolongation of the lag time preceding the propagation of a free radical chain reaction. In fact, under certain conditions both water soluble antioxidants (e.g. vitamin C and urate) and the lipid soluble antioxidant tocopherol (vitamin E), promote or even induce peroxidation. Based on the published data, including our results, we conclude that terms such as 'antioxidative capacity' or 'antioxidative potency' are context-dependent. Furthermore, criteria of the efficacy of antioxidants based on oxidation in solution are not necessarily relevant to the effects of antioxidants on peroxidation in biological systems or model lipid assemblies, because the latter processes occur at water/lipid interfaces. We think that evaluation of antioxidants requires kinetic studies of the biomarker used and that the most relevant characteristic of 'oxidative stress' in the biological context is the kinetics of ex vivo peroxidation of lipids. We therefore propose studying the kinetics of lipid-peroxidation in the absence of the studied antioxidant and in its presence at different antioxidant concentrations. These protocols mean that antioxidants are assayed by methods commonly used to evaluate oxidative stress. The advantage of such evaluation is that it enables quantization of the antioxidants' efficacy in a model of relevance to biological systems. In view of the sensitivity of the lag time preceding peroxidation, we propose studying how much antioxidant is required to double the lag observed prior to rapid peroxidation. The latter quantity (C(2lag)) can be used to express the strength of antioxidants in the relevant system (e.g. LDL, serum or liposomes).

Intestinal myofibroblasts: targets for stem cell therapy.

The subepithelial intestinal myofibroblast is an important cell orchestrating many diverse functions in the intestine and is involved in growth and repair, tumorigenesis, inflammation, and fibrosis. The myofibroblast is but one of several α-smooth muscle actin-positive (α-SMA(+)) mesenchymal cells present within the intestinal lamina propria, including vascular pericytes, bone marrow-derived stem cells (mesenchymal stem cells or hematopoietic stem cells), muscularis mucosae, and the lymphatic pericytes (colon) and organized smooth muscle (small intestine) associated with the lymphatic lacteals. These other mesenchymal cells perform many of the functions previously attributed to subepithelial myofibroblasts. This review discusses the definition of a myofibroblast and reconsiders whether the α-SMA(+) subepithelial cells in the intestine are myofibroblasts or other types of mesenchymal cells, i.e., pericytes. Current information about specific, or not so specific, molecular markers of lamina propria mesenchymal cells is reviewed, as well as the origins of intestinal myofibroblasts and pericytes in the intestinal lamina propria and their replenishment after injury. Current concepts and research on stem cell therapy for intestinal inflammation are summarized. Information about the stem cell origin of intestinal stromal cells may inform future stem cell therapies to treat human inflammatory bowel disease (IBD).

Mesenchymal cells of the intestinal lamina propria.

The mesenchymal elements of the intestinal lamina propria reviewed here are the myofibroblasts, fibroblasts, mural cells (pericytes) of the vasculature, bone marrow-derived stromal stem cells, smooth muscle of the muscularis mucosae, and smooth muscle surrounding the lymphatic lacteals. These cells share similar marker molecules, origins, and coordinated biological functions previously ascribed solely to subepithelial myofibroblasts. We review the functional anatomy of intestinal mesenchymal cells and describe what is known about their origin in the embryo and their replacement in adults. As part of their putative role in intestinal mucosal morphogenesis, we consider the intestinal stem cell niche. Lastly, we review emerging information about myofibroblasts as nonprofessional immune cells that may be important as an alarm system for the gut and as a participant in peripheral immune tolerance.

Intestinal mesenchymal cells.

The non-white blood cell mesenchymal elements of the intestinal lamina propria are the myofibroblasts, fibroblasts, pericytes, stromal stem cells, muscularis mucosae, and the smooth muscle of the villus core associated with the lymphatic lacteal. We review the functional anatomy of these mesenchymal cells, what is known about their origin in the embryo and their replacement in adults, their putative role in intestinal mucosal morphogenesis, and the intestinal stem cell niche, and we consider new information about myofibroblasts as nonprofessional immune cells. Although our knowledge of the function of mesenchymal cells in intestinal disease is rudimentary, we briefly consider here their roles in cancer and intestinal inflammation.

Copper-induced peroxidation of phosphatidylserine-containing liposomes is inhibited by nanomolar concentrations of specific antioxidants.

Copper-induced peroxidation of liposomal palmitoyllinoleoyl-phosphatidylcholine (PLPC) is inhibited by alpha-tocopherol at micromolar concentrations. In our previous study we found that when the liposomes contain phosphatidylserine (PS), nanomolar concentrations of Toc were sufficient to inhibit peroxidation. In an attempt to gain understanding of the origin of this extreme antioxidative potency, we tested the antioxidative potency of 36 additional antioxidants and the dependence of their potency on the presence of PS in the liposomes. The results of these studies reveal that only 11 of the tested antioxidants possess similar antioxidative potency to that of Toc. These include trolox, butylated hydroxytoluene (BHT), curcumin, nordihydroguaiaretic acid (NDGA), diethylstilbestrol (DES), 2 of the 13 tested flavonoids (luteolin and 7,3',4'-trihydroxyflavone; T-414), alpha-naphthol, 1,5-, 1,6- and 1,7-dihydroxynaphthalenes (DHNs). Propyl gallate (PG), methyl syringate, rosmarinic acid, resveratrol, other flavonoids, as well as beta-naphthol, 1,2-, 1,3-, 1,4-, 2,3-, 2,6-, and 2,7-DHNs were either moderately antioxidative or pro-oxidative. For liposomes made of PLPC (250 microM) and PS (25 microM) the "lag" preceding copper-induced peroxidation (5 microM copper) was doubled upon addition of 30-130nM of the "super-active" antioxidants. We propose that the mechanism responsible for the extreme antioxidative potency against copper-induced peroxidation in PS-containing liposomes involves replenishment of the antioxidant in a ternary PS-copper-antioxidant complex. Based on structure-activity relationship of the 37 tested antioxidants, the "super-antioxidative potency" is attributed to the recycling of relatively stable semiquinone or semiquinone-like radicals.

Oxidation of liposomal cholesterol and its effect on phospholipid peroxidation.

Lipid peroxidation is believed to play an important role in the pathogenesis of many diseases. Much research has therefore been devoted to peroxidation of different lipids in biomembranes and in model systems (liposomes) of different compositions. Yet, in spite of the relative simplicity of the liposomes, the existing literature is insufficient to reach definite conclusions regarding basic questions including the susceptibility of cholesterol to oxidation, its effect on the peroxidation of polyunsaturated phospholipids such as palmitoyllinoleoylphosphatidylcholine (PLPC) and how cholesterol influences the effect of water-soluble antioxidants such as urate on the peroxidation. The aim of the present study was to clarify these issues. Its major findings are that: (i) AAPH-induced peroxidation of cholesterol is slow and independent of the peroxidation of PLPC. In turn, AAPH-induced peroxidation of PLPC is not affected by cholesterol, independent of the presence of urate in the system. (ii) Cholesterol is not susceptible to copper-induced oxidation, but its inclusion in PLPC liposomes affects the peroxidation of PLPC, slowing down the initial stage of oxidation but promoting later stages. (iii) Addition of urate accelerates copper-induced peroxidation of PLPC in the absence of cholesterol, whereas in cholesterol-containing liposomes it inhibits PLPC oxidation. We attribute the complexity of the observed kinetics to the known cholesterol-induced rigidization of liquid crystalline bilayers.

Effect of a short-term graded exhaustive exercise on the susceptibility of serum lipids to oxidation.

The objective of our study was to evaluate the effect of short-term intensive exercise on the susceptibility of serum lipids to ex-vivo peroxidation. We assessed the association between aerobic capacity, serum composition, and serum lipid oxidizability as well as the association between aerobic capacity and the effect of short-term maximal exercise on the kinetics of ex-vivo copper-induced peroxidation of serum lipids. The study involved 30 healthy male volunteers (age 22-39 years, BMI 19.4-29.8). Following 12-hr fasting, blood was withdrawn for determination of blood lipids, LDL, HDL, and TG, and Vitamin E, and for oxidizability assay of the serum lipids. Subsequently, each volunteer underwent an incremental all-out cardiopulmonary exercise stress test (CPET), performed on a motor-driven treadmill (Quinton Q65, USA). The test protocol was a modified Balke protocol. The results of this test were expressed in terms of mass-dependent maximal oxygen uptake (VO2max, ml.kg(-1).min (-1)) and of ventilatory anaerobic threshold (VAT, ml.kg(-1).min(-1)). Immediately after exercise, blood was re-drawn for the determination of serum Vitamin E and for ex-vivo oxidizibility assay, expressed in terms of maximal absorption of oxidation products (OD(max), absorbance units), maximal rate of their production (V(max), OD min(-1)) and the time at which the rate was maximal (t(max), min). Maximal graded exercise had no significant effect on the susceptibility of serum lipids to peroxidation as measured by OD(max) (p = 0.38 at 245 nm, and 0.27 at 268 nm),V(max) (p = 0.34 at 245 nm, and 0.49 at 268 nm) and t(max) (p = 0.17 at 245 nm, and 0.07 at 268 nm). Also no effect was found on the concentration of serum Vitamin E (p = 0.39). Aerobic capacity was not associated either with the susceptibility of serum lipids to ex-vivo peroxidation or with serum Vitamin E concentration. The present findings indicate that a short graded maximal exercise, lasting 8-12 min, is not sufficient to increase the susceptibility of the serum lipids to peroxidation. Thus it may be assumed that the antioxidant capacity of most healthy subjects provides proper protection from a short exhaustive exercise challenge. Also, aerobic capacity in the range represented by our subjects does not seem to influence the susceptibility of serum lipids to peroxidation.

Lipid peroxidation cannot be used as a universal criterion of oxidative stress.

Oxidative stress is a term used to denote the imbalance between the concentrations of reactive oxygen and nitrogen species and the defense mechanisms of the body. Although it is generally accepted that such an imbalance plays a pivotal role in many pathologies, the term "oxidative stress" remains ill defined. In an attempt to evaluate the relationship between various assays of oxidative stress, we have analyzed the correlations between the results reported in those publications in which "oxidative stress" has been assayed by at least two methods. We found good correlations between the concentrations of several peroxidation products, including malondialdehyde, F2-Isoprostanes, lipid hydroperoxides, conjugated dienes, glutathione and protein carbonyls, but not with other criteria of "individual oxidative status" such as the concentration of antioxidants and products of DNA fragmentation (the "comet" assay). In light of these findings, we divide the assays used for evaluation of "oxidative stress" into the following three categories: (i) assays based on measuring the concentrations of oxidation products of lipids, proteins and DNA, as well as the concentrations of antioxidants, (ii) assays used to evaluate the oxidative and reductive capacity of biological fluids and (iii) assays used to evaluate the ex vivo susceptibility of lipids to oxidation upon their exposure to a source of free radicals. Our analyses demonstrate that oxidative stress cannot be defined in universal terms. Two results are of special interest:1.the commonly used criteria based on lipid peroxidation can not be regarded as a general estimate of the individual "oxidative status".2.the levels of antioxidants exhibit a non-monotonic relation with other criteria for oxidative stress. Further research is required to evaluate the significance of the latter finding.

Class II MHC-expressing myofibroblasts play a role in the immunopathogenesis associated with staphylococcal enterotoxins.

Food poisoning due to staphylococcal enterotoxins (SEs) affects hundreds of thousands of people each year. Little is known about how SEs initiate immune responses and cause pathogenesis. Here, we demonstrate that cultured human intestinal myofibroblasts (IMFs) bind SEs in an MHC class II-dependent fashion. IMFs respond to SE exposure with increased secretion of IL-6, IL-8, and TNF-alpha. A significant proliferative T cell response was observed when MHC class II-expressing IMFs were pulsed with SEA and cocultured with human CD4(+) T cells. In conclusion, our findings support the hypothesis that IMFs may play an important role in pathology associated with staphlococcocal enterotoxigenic disease.

Genetic diversity and involvement in bread spoilage of Bacillus strains isolated from flour and ropy bread.

AIMS: To study Bacillus contamination of wheat flour and ropy bread, to analyse genetic diversity of isolated strains and to evaluate the ability of these strains to produce ropy bread. METHODS AND RESULTS: Classical and molecular methods [16S rDNA sequencing and random amplified polymorphic DNA (RAPD)-PCR] were used to identify and type-isolated strains. The predominant species isolated were Bacillus subtilis and B. licheniformis. RAPD analysis demonstrated that the same sample may harbor different strains. Ten of 15 strains of B. subtilis and four of six strains of B. licheniformis were able to cause rope spoilage of the laboratory-baked bread. CONCLUSION: RAPD typing can be useful in the tracking of Bacillus strains during bakery processing and in the understanding of the role of different Bacillus strains in the rope spoilage of bread. SIGNIFICANCE AND IMPACT OF THE STUDY: The results indicate the variability of Bacillus strains isolated from flour and responsible for rope spoilage of bread.

Acute myocardial infarction is associated with increased susceptibility of serum lipids to copper-induced peroxidation in vitro.

BACKGROUND: Low-density lipoprotein (LDL) oxidation in the arterial intima plays a pivotal role in atherogenesis. Under physiologic conditions, several mechanisms protect LDL against oxidation, including hydrolysis of oxidation products by high-density lipoprotein (HDL)-associated enzymes. Some of these protective mechanisms are less effective under acute phase conditions. HYPOTHESIS: Conditions of acute phase response, including acute myocardial infarction (MI), may be expected to result in increased susceptibility of serum lipids to oxidation. The present study was undertaken to test this possibility. METHODS: Using our previously developed spectroscopic method, we have monitored prospectively the kinetics of copper-induced oxidation of serum lipids obtained from 15 men during and after acute MI. This was tested within 6 h from the onset of chest pain, on Days 1, 3, and 7 of infarction and 1 year after recovery. RESULTS: The lag phase preceding oxidation of serum lipids was much shorter during the first week after MI when compared with values obtained after recovery (52-59 vs. 107 min, respectively, p <0.001). During the first week after MI, we observed no significant correlations between kinetic parameters and serum lipid composition, in contrast both to the correlations previously reported for hyperlipidemic patients and to the similar correlations observed in the present study after recovery. CONCLUSIONS: Acute MI is associated with an increased susceptibility of serum lipids to oxidation in vitro. This propensity for oxidation may reflect enhanced in vivo formation of free radicals and/or reduced efficiency of defense mechanisms. Both these possibilities may carry detrimental effects on the course, complications, and prognosis of the patients after acute MI.

Kinetics of lipid peroxidation in mixtures of HDL and LDL, mutual effects.

In view of the proposed central role of LDL oxidation in atherogenesis and the established role of HDL in reducing the risk of atherosclerosis, several studies were undertaken to investigate the possible effect of HDL on LDL peroxidation. Since these investigations yielded contradictory results, we have conducted systematic kinetic studies on the oxidation in mixtures of HDL and LDL induced by different concentrations of copper, 2, 2'-azo bis (2-amidinopropane) hydrochloride (AAPH) and myeloperoxidase (MPO). These studies revealed that oxidation of LDL induced either by AAPH or MPO is inhibited by HDL under all the studied conditions, whereas copper-induced oxidation of LDL is inhibited by HDL at low copper/lipoprotein ratio but accelerated by HDL at high copper/lipoprotein ratio. The antioxidative effects of HDL are only partially due to HDL-associated enzymes, as indicated by the finding that reconstituted HDL, containing no such enzymes, inhibits peroxidation induced by low copper concentration. Reduction of the binding of copper to LDL by competitive binding to the HDL also contributes to the antioxidative effect of HDL. The acceleration of copper-induced oxidation of LDL by HDL may be attributed to the hydroperoxides formed in the "more oxidizable" HDL, which migrate to the "less oxidizable" LDL and enhance the oxidation of the LDL lipids induced by bound copper. This hypothesis is supported by the results of experiments in which native LDL was added to oxidizing lipoprotein at different time points. When the native LDL was added prior to decomposition of the hydroperoxides in the oxidizing lipoprotein, the lag preceding oxidation of the LDL was much shorter than the lag observed when the native LDL was added at latter stages, after the level of hydroperoxides became reduced due to their copper-catalyzed decomposition. The observed dependence of the interrelationship between the oxidation of HDL and LDL on the oxidative stress should be considered in future investigations regarding the oxidation of lipoprotein mixtures.

In vitro anti-Helicobacter pylori activity of the probiotic strain Bacillus subtilis 3 is due to secretion of antibiotics.

A limited number of antibiotics can be used against Helicobacter pylori infection, and resistance jeopardizes the success of treatment. Therefore, a search for new agents is warranted. The use of probiotics to enhance gastrointestinal health has been proposed for many years, but the scientific basis of the prophylactic and therapeutic actions of probiotics has not yet been clearly delineated. Probiotic strain Bacillus subtilis 3, whose safety has previously been demonstrated, is known to have antagonistic properties against species of the family Enterobacteriaceae. In the present study, it was also found to inhibit H. pylori. The anti-H. pylori activity present in the cell-free supernatant was not related to pH or organic acid concentration. It was heat stable and protease insensitive. At least two antibiotics, detected by thin-layer chromatography (R(f) values, 0.47 and 0.85, respectively) and confirmed by high-performance liquid chromatographic analysis, were found to be responsible for this anti-H. pylori activity. All H. pylori strains tested were sensitive to both compounds. One of these compounds was identified as amicoumacin A, an antibiotic with anti-inflammatory properties. MICs for H. pylori determined in solid and liquid media ranged between 1.7 and 6.8 microg/ml and 0.75 and 2.5 microg/ml, respectively. The underestimation of MICs determined in solid medium may be due to physicochemical instability of the antibiotic under these test conditions. An additive effect between amicoumacin A and the nonamicoumacin antibiotic against H. pylori was demonstrated.