Biological activity

Scilla maderensis Menezes (Hyacinthaceae) is endemic to the Portuguese Archipelago of Madeira. The taxonomic proximity between Scilla L. and Urginea Steinh. genus, and also the knowledge that bulbs of Urginea maritima (L.) Baker (Scilla maritima L.) contain cardiac glycosides of the bufadienolide type, led us to a phytochemical and pharmacological study of S. maderensis. Extracts obtained from the bulbs were screened by TLC and tested in the isolated frog heart preparation. The TLC screening revealed spots with colours and R f values similar to those obtained for proscillaridin and scillaren A. In the frog heart preparation the extracts showed a positive inotropic effect and toxic doses induced the arrest of the heartbeat in systole. We can conclude that the bulbs of S. maderensis contain substances exerting pharmacological effects on the heart.

Background: During bladder filling, the trigone contracts help keep the ureteral orifices open and the bladder neck shut. The trigone generates spontaneous activity as well as responding to neuromuscular transmitters, but the relationship between these phenomena are unclear. Objectives: To characterise the cellular mechanisms that regulate and modify spontaneous activity in trigone smooth muscle. Design, setting, and participants: Muscle strips from the superficial trigone of male guinea-pigs were used for tension experiments and immunofluorescent studies. Measurements: In isolated trigonal cells, intracellular Ca 2+ was measured by epifluorescence microscopy using the fluorescent Ca 2+ indicator Fura-2. Results and limitations: Spontaneous intracellular Ca 2+ transients and contractions were observed in trigonal single cells and strips and were significantly higher compared to the bladder dome. Ca-free superfusate and verapamil terminated spontaneity. T-type Ca 2+ channel block with NiCl 2 depressed slightly Ca 2+ transients but not spontaneous contractions. Neither the BK Ca channel blocker iberiotoxin nor the SK Ca channel blocker apamin had any effect on single cell activity. By contrast, the Cl À channel blocker niflumic acid attenuated significantly both Ca 2+ transients and muscle contractions. Agonist stimulation (carbachol, phenylephrine) up-regulated activity. Gap junction labelling (Cx43) was approximately 5 times denser in the trigone than in detrusor smooth muscle. The gap junction blocker 18-ß-glycyrrhetinic acid modulated spontaneous contractions in the trigone but not in the bladder dome. Conclusions: Trigone myocytes employ membrane L-type-Ca 2+ channels and Cl À channels to generate spontaneous activity. Intercellular electrical coupling ensures its propagation and, thus, sustains contraction of the whole trigone.

Ethnopharmacological relevance: The essential oil (EO) from Cymbopogon citratus (DC) Stapf is reported to have a wide range of biological activities and is widely used in traditional medicine as an infusion or decoction. However, despite this widely use, there are few controlled studies confirming its biological activity in central nervous system. Materials and methods: The anxiolytic-like activity of the EO was investigated in light/dark box (LDB) and marble-burying test (MBT) and the antidepressant activity was investigated in forced-swimming test (FST) in mice. Flumazenil, a competitive antagonist of benzodiazepine binding and the selective 5-HT 1A receptor antagonist WAY100635 was used in experimental procedures to determine the action mechanism of EO. To exclude any false positive results in experimental procedures, mice were submitted to the rota-rod test. We also quantified some neurotransmitters at specific brain regions after EO oral acute treatment. Results: The present work found anxiolytic-like activity of the EO at the dose of 10 mg/kg in a LDB. Flumazenil, but not WAY100635, was able to reverse the effect of the EO in the LDB, indicating that the EO activity occurs via the GABA A receptor-benzodiazepine complex. Only at higher doses did the EO potentiate diethyl-ether-induced sleeping time in mice. In the FST and MBT, EO showed no effect. Finally, the increase in time spent in the light chamber, demonstrated by concomitant treatment with ineffective doses of diazepam (DZP) and the EO, revealed a synergistic effect of the two compounds. The lack of activity after long-term treatment in the LDB test might be related to tolerance induction, even in the DZP-treated group. Furthermore, there were no significant differences between groups after either acute or repeated treatments with the EO in the rota-rod test. Neurochemical evaluation showed no amendments in neurotransmitter levels evaluated in cortex, striatum, pons, and hypothalamus. Conclusions: The results corroborate the use of Cymbopogon citratus in folk medicine and suggest that the anxiolytic-like effect of its EO is mediated by the GABA A receptor-benzodiazepine complex.

Terpenes and sterols are complex molecules synthesized by equally complex biosynthetic pathways. Recent progress in using the tools of genetics, molecular genetics and genetic engineering to dissect triterpene metabolism in the cytosol, and terpene metabolism in the ...

Despite their perceived inaccessibility, the marine intertidal and benthic environments of Antarctica, southern Africa and South America have continued to provide marine natural products for chemists with unique opportunities to study the secondary metabolite constituents and chemical ecology of a diverse array of marine gastropod molluscs. This review covers the literature up to 31 January 2005 and describes the structures and, where applicable, biological activities of 100 secondary metabolites isolated from 21 species of marine gastropod molluscs. Not unexpectedly, the chemistry of chemically defended shell-less opisthobranchs dominates the natural product studies of molluscs collected from these regions of the southern hemisphere.

Solid-state fermentation (SSF) has built up credibility in recent years in biotech industries due to its potential applications in the production of biologically active secondary metabolites, apart from feed, fuel, food, industrial chemicals and pharmaceutical products and has emerged as an attractive alternative to submerged fermentation. Bioremediation, bioleaching, biopulping, biobeneficiation, etc. are the major applications of SSF in bioprocesses which have set another milestone. Utilization of agro-industrial residues as substrates in SSF processes provides an alternative avenue and value-addition to these otherwise under-or non-utilized residues. Innovation is the key to success and it is imperative to be up-to-date with the changing demands of the industries and meet their needs for better product and services. Better understanding of biochemical engineering aspects, particularly on mathematical modeling and design of bioreactors (fermenters) has made it possible to scale-up SSF processes and some designs have been developed for commercialization, making the technology economically feasible. In future, SSF technology would be well developed at par with SmF if rationalization and standardization continues in current trend. This review describes the state-of-art scenario in totality on SSF although the focus is on the most recent developments of last 5 years or so on SSF processes and products developments.

In this work we describe the identification of the biologically active triterpenes and sterols present in the hexane extracts of six species of Miconia using gas chromatography. The main compounds present in these extracts are β-amyrin, α-amyrin, and β-sitosterol. The technique employed herein is shown to be a valuable and rapid tool for determining biologically active triterpenes and sterols present in non-polar extracts. EXPERIMENTAL Plant materials. Miconia species (M. albicans, M. pepericarpa, M. sellowiana, M. falax, M. rubiginosa and M. ligustroides) were collected along the Franca-Claraval highway in São Paulo, Brazil, and they were identified by

Objective: Biodegradable polycaprolactone/starch composites can be used for bone tissue engineering applications. The effect of the ratio of components on composite properties is of tremendous importance. Methods: Polycaprolactone/starch composite of 80/20 and 70/30 ratios were fabricated by dissolving them in chloroform followed by evaporation of the solvent. Results: The composites were characterized by fourier transform infrared spectroscopy. Their bioactivity was evaluated by studying the apatite formation ability after immersing the specimens in simulated body fluid. The results of compressive test on samples showed that the composite's modulus and strength approximated that of human trabecular bone. Mass loss in distilled water and starch degradation rate in PBS was evaluated, which showed that the starch ratio was effective in composite degradation. MTT analysis and alkaline phosphatase levels showed that this composite had no toxicity and could increase G-299 cell line osteoblastic activities. Conclusion: The increase in cellular osteoblastic activities and the ability for apatite formation on the composite surface, in addition to the polycaprolactone/starch samples' mechanical properties shows their capability to be used as substitutes for bone. Because this composite degradation rate is controlled by changing the starch ratio, it has the potential for use in bone tissue engineering applications. Samples that have a 70/30 ratio are considered optimal due to their enhanced cellular response and better mechanical properties.

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A method was developed to quantify the "antikeratinizing" effects of various retinoids (all-trans-retinoic acid, 13-cis-retinoic acid, motretinide, etretinate) in rhino mouse skin, which contains many keratinized pilosebaceous structures or horn-filled utriculi. Mean utriculus diameters in whole mount epidermis were determined and dose-response relationships were constructed after topical or oral administration of test retinoids. Alltrans-retinoic acid was 3.7x, 12.5x, and 50x more potent than 13-cis-retinoic acid, etretinate, and motretinide, respectively, after topical administration. Administered orally, all-trans-retinoic acid was 2.3x more potent than 13-cis-retinoic acid. At 5 mg/kg, each retinoid produced a significant reduction in utriculus size. The rhino mouse model represents a novel and useful assay to quantify anti keratinizing activity and potency differences of biologically active retinoids.

To extend our knowledge on the cytokines possibly involved in the pathophysiology of B-cell chronic lymphocytic leukemia (B-CLL), the mRNA expression of a panel of 10 cytokines was investigated on purified B-CLL cells using a reversetranscriptase polymerase chain reaction method. Whereas negative RT-PCR signals were recorded for interleukin-la

Global climate change may impact the cycling of C, N, and S in forest ecosystems because increased soil temperatures could alter rates of microbially mediated processes. We studied the effects of temperature on microbial respiration and net N and S mineralization in surface soils from four northern hardwood forests in the Great Lakes region. Soil samples were incubated in the laboratory at five temperatures (5, 10, 15, 20, and 25°C) for 32 wk. Headspace gas was analyzed for CO 2-C at 2-wk intervals, and soils were extracted to determine inorganic N and S. Cumulative respired C and mineralized N and S increased with temperature at all sites and were strongly related (r 2 = 0.67 to 0.90, significant at P = 0.001) to an interaction between temperature and soil organic C. Production of respired C and mineralized N was closely fit by first-order kinetic models (r 2 > 0.94, P = 0.001), whereas mineralized S was best described by zero-order kinetics. Contrary to common assumptions, rate constants estimated from the first-order models were not consistently related to temperature, but apparent pool sizes of C and N were highly temperature dependent. Temperature effects on microbial respiration could not be accurately predicted using temperature-adjusted rate constants combined with a constant pool size of labile C. Results suggest that rates of microbial respiration and the mineralization of N and S may be related to a temperature-dependent constraint on microbial access to substrate pools. Simulation models should rely on a thorough understanding of the biological basis underlying microbially mediated C, N, and S transformations in soil.

Purpose Pancreatic cancer (PC) is one of the deadliest of all tumors. Previously, we were the first to show that Thymoqui-none (TQ) derived from black seed (Nigella sativa) oil has anti-tumor activity against PC. However, the concentration of TQ required was ...

A cyanobacterial bloom occurring in 1998 in lake Tres Pascualas (Concepci6n/Chile) was found to be dominated by Microcystis sp. The bloom contained both non-toxic (cyanopeptolin-type) and hepatotoxic (microcystin-type) peptides. Cyanopeptolin structure of the non-toxic peptides (called cyanopepto lin VW-l and VW-2, respectively) was revealed by matrix assisted laser desorption ionization mass spectrometry (MALDI-TOF-MS) of whole cells, showing dominant molecular ions at mlz = 975 and mlz 995, respectively. On post source decay (PSD), both cyanopeptolins showed fragments deriving from Ahp-Phe-MTyr (3-amino-6-hydroxy-2-piperidone), the characteristic partial structure of cyanopeptolins. The amounts of each of the two cyanopeptolins could only roughly be estimated to be >0.1 % of bloom material dry weight. In addition the blooms contained microcystins (20 pg/g bloom dry weight as determined by RP-HPLC, 13 pg/g according to ELISA determination). MALDI-TOF-MS revealed several structural variants of microcystin: MCYST-RR (microcystin with Arg and Arg, indicated by mlz 1,038 and confirmed by PSD revealing a mlz = 135 fragment deriving from the Adda side chain, MCYST-FR (microcystin with Phe and Arg, indicated by mlz = 1,015). The presence of [ASp(31]-MCYST-LR (microcystin with Leu and Arg, Asp non-methylated, indicated by mlz 981), and [ASp(31]-MCYST-YR (microcystin with Tyr and Arg, Asp non-methylated, indicated by mlz 1,031) were likely. The relative amounts of the peptides varied between February, April, and May. Whole cell extracts from the bloom material revealed specific enzyme inhibitory activities. The serinproteases trypsin, plasmin, elastase were inhibited, assumable due to the cyanopeptolins found. Elastase and the cysteine-protease papain were not inhibited, inhibitions of protein kinase and glutathione Stransferase (GST) were low. Strong inhibition was observed with protein-phosphatase-1, likely due to the microcystins present in the samples.

Patients and Methods Cirrhotic patients with acute esophageal variceal bleeding that was initially controlled with emergency sclerotherapy and in whom a hemodynamic evaluation could be performed within the first 24 hours of admission, were considered for inclusion in this study. All patients were admitted to our hospital with hematemesis and/or melena. Diagnostic endoscopy was performed between 1 and 5 hours later, as soon as safely possible after initial resuscitation. Variceal hemorrhage was defined when endoscopy showed active hemorrhage

Minimum Inhibitory Concentrations (MICs) were determined for nisin and an aqueous garlic extract (AGE) for six strains of Listeria monocytogenes, including a nisin-resistant mutant.When used in combination in broth a synergistic e¡ect was observed between nisin and AGE in all strains. Increasing the pH reduced the activity of both nisin and garlic. During storage of the aqueous garlic extract at 48C and at 208C for14 days, the MIC increased over the ¢rst 8 days but remained stable thereafter, indicating at least two antimicrobial components, one of which was relatively stable. Aqueous garlic extract was not appreciably bactericidal although there was a positive interaction with nisin in terms of its bactericidal e¡ect in broth at 48C. The e¡ect of combining nisin and garlic in a food system, hummus, was also studied. Sub-MIC combinations of AGE and nisin were e¡ective at preventing listerial growth and did enhance the slight bactericidal e¡ect of nisin.The results indicate that combined use of nisin with garlic could help overcome problems of nisin resistance in Gram-positive organisms. Such interactions could also be a signi¢cant factor in traditional lactic fermented foods where garlic is an ingredient.

The effect of Indian herbs namely, Asparagus racemosus, Tinospora cordifolia, Withania somnifera and Picrorhiza kurrooa on the functions of macrophages obtained from mice treated with the carcinogen ochratoxin A (OTA) was investigated. The chemotactic activity of murine macrophages was significantly decreased by 17 weeks of treatment with OTA compared with controls. Production of interleukin-1 (IL-1) and tumor necrosis factor (TNF) was also markedly reduced. Treatment with Asparagus racemosus, Tinospora cordifolia, Withania somnifera and Picrorhiza kurrooa significantly inhibited OTA-induced suppression of chemotactic activity and production of IL-1 and TNF-h by macropahges. Moreover, we found that Withania somnifera treated macrophage chemotaxis and that Asparagus racemosus induced excess production of TNF-h when compared with controls. © 1997 Elsevier Science Ireland Ltd.

Centaurea solstitialis (yellow star thistle) has been proven to cause equine nigropallidal encephalomalacia in horses. Over the last fifty years, nigropallidal encephalomalacia has been of interest to human medicine due to the possible connection with Parkinson's disease. Previous studies indicated the presence of neurotoxic nitrogenous compounds in polar extracts of the plant. In order to give a more detailed description of the nitrogen-containing fraction of C. solstitialis, various samples were collected at different development stages. Different aliquots of the same aqueous extract were directly derivatized with ophthaldialdehyde and dansyl chloride and analyzed separately by reversed-phase HPLC. A complete profile of the free nitrogenous fraction of C. solstitialis was given and results obtained with the two derivatization procedures were compared. No particularly high level of free aspartic and glutamic acids, two potent neuroexcitotoxic amino acids, were found in polar extracts of the plant. Tyramine resulted to be the most important biologically active amine present in C. solstitialis (with a mean concentration of 2.0 mg/100 g of dry weight). q

Heparin-like polysaccharides possess the capacity to inhibit cancer cell proliferation, angiogenesis, heparanase-mediated cancer cell invasion, and cancer cell adhesion to vascular endothelia via adhesion receptors, such as selectins. The clinical applicability of the antitumor effect of such polysaccharides, however, is compromised by their anticoagulant activity. We have compared the potential of chemically O-sulfated and N,O-sulfated bacterial polysaccharide (capsular polysaccharide from E. coli K5 [K5PS]) species to inhibit metastasis of mouse B16-BL6 melanoma cells and human MDA-MB-231 breast cancer cells in two in vivo models. We demonstrate that in both settings, O-sulfated K5PS was a potent inhibitor of metastasis. Reducing the molecular weight of the polysaccharide, however, resulted in lower antimetastatic capacity. Furthermore, we show that O-sulfated K5PS efficiently inhibited the invasion of B16-BL6 cells through Matrigel and also inhibited the in vitro activity of heparanase. Moreover, treatment with O-sulfated K5PS lowered the ability of B16-BL6 cells to adhere to endothelial cells, intercellular adhesion molecule-1, and P-selectin, but not to E-selectin. Importantly, O-sulfated K5PSs were largely devoid of anticoagulant activity. These findings indicate that O-sulfated K5PS polysaccharide should be considered as a potential antimetastatic agent.

Angiogenesis plays a central role in wound healing. Among many known growth factors, vascular endothelial growth factor (VEGF) is believed to be the most prevalent, efficacious, and long-term signal that is known to stimulate angiogenesis in wounds. The wound site is rich in oxidants, such as hydrogen peroxide, mostly contributed by neutrophils and macrophages. We proposed that oxidants in the wound microenvironment support the repair process. Proanthocyanidins or condensed tannins are a group of biologically active polyphenolic bioflavonoids that are synthesized by many plants. Previously we have reported that a grape seed proanthycyanidin extract containing 5000 ppm resveratrol (GSPE) potently upregulates oxidant and tumor necrosis factor-␣ inducible VEGF expression in human keratinocytes (Free Radic. Biol. Med. 31:38 -42, 2001). Our current objective was to follow up on that finding and test whether GSPE influences dermal wound healing in vivo. First, using a VEGF promoter-driven luciferase reporter construct we observed that the potentiating effect of GSPE on inducible VEGF expression is at the transcriptional level. The reporter assay showed that GSPE alone is able to drive VEGF transcription. Next, two dermal excisional wounds were inflicted on the back of mice and the wounds were left to heal by secondary intention. Topical application of GSPE accelerated wound contraction and closure. GSPE treatment was associated with a more well-defined hyperproliferative epithelial region, higher cell density, enhanced deposition of connective tissue, and improved histological architecture. GSPE treatment also increased VEGF and tenascin expression in the wound edge tissue. Tissue glutathione oxidation and 4-hydroxynonenal immunostaining results supported that GSPE application enhanced the oxidizing environment at the wound site. Oxidants are known to promote both VEGF as well as tenascin expression. In summary, our current study provides firm evidence to support that topical application of GSPE represents a feasible and productive approach to support dermal wound healing.

Sponges biosynthesize a wealth of secondary metabolites, many with novel structures and strong biological activity. Such compounds may serve multiple ecological roles including anti-predation, anti-fouling functionalities and are implicated in border defense or attack during spatial competition. Relative size of benthic organisms may also play an important role in competitive interactions. To determine if a relationship exists between individual size and bioactive metabolite production in the context of spatial competition, we examined three sponge species with different morphologies: the massive Coscinoderma matthewsi, the club-shaped branching Hyrtios erecta, and the fan-shaped Ianthella basta. Extracts from sponges of various sizes and competitive environments were examined using a cell based bioassay as a proxy of bioactivity. For I. basta, sponge size was correlated with bioactivity; the largest individuals generally being the most bioactive. In contrast, there was no correlation between size and bioactivity for either C. matthewsi or H. erecta. Bioactivity of sponges in this study were however highly variable among individuals, regardless of levels of competition. The prevalence of encroaching organisms was not correlated with sponge size for any of the three sponge species, suggesting that potential bioactivity is not influenced by surrounding competition.

Cuprizone is used to obtain demyelination in mice. Cuprizone-treated mice show symptoms similar to several neurodegenerative disorders such as severe status spongiosus. Although it has a simple chemical formula, its neurotoxic mechanism is still unknown. In this work, we examined both physico-chemical properties and biological effects of cuprizone. Our results indicate that cuprizone has very complicated and misunderstood solution chemistry. Moreover, we show here the inability of cuprizone to cross neither the intestinal epithelial barrier nor the neuronal cell membrane, as well its high tolerability by cultured neurons. If added to mice diet, cuprizone does not accumulate in liver or in brain. Therefore, its neurotoxic effect is explainable only in terms of its capability to chelate copper, leading to chronic copper deficiency.

To discover analogues of melatonin with a longer half-life, novel non-indole analogues of the compound, in which the amide group of the side-chain has been reversed, have been prepared and evaluated in binding assays to determine their activity on melatonin receptors.

If we are to make advances in the design of information systems for the processing of functional genomic data, we must carefully examine the concepts of gene and function. Therefore, we must consider the biological models that are used to acquire these data from an epistemological point of view. This article introduces three elements of this view: (i) we reviewed the major concepts and the axioms of the systemic paradigm; (ii) we considered their relevance for the modelling of the biological functions within the framework of an intracellular signalling process; (iii) we present an operational input founded on this methodological viewpoint to illustrate the coherence of a theoretical framework and the use of its formalism for the description and the representation of biological activities. This formalism will guide the modelling and the interpretation of molecular interactions in terms of organisational operations producing and transforming the genetic information; thus, providing a better understanding of the complex relationship between the generation, the circulation and the computation of information when biological systems are set up. To cite this article: M. Roux-Rouquié, J.-L. Le Moigne, C. R. Biologies 325 (2002) 419-430. © 2002 Académies des sciences / Éditions scientifiques et médicales Elsevier SAS systemic modelling / epistemology / biological function / knowledge organisation / information system Résumé -Le paradigme systémique et sa pertinence pour la modélisation des fonctions biologiques. Une avancée dans le domaine de la conception des systèmes d'information pour l'exploitation des données de génomique fonctionnelle nécessite une discussion attentive des concepts de gène et de fonction, et donc une réflexion épistémologique sur les modèles biologiques à l'aide desquels sont établis ces systèmes d'information. Dans cet article, nous avons introduit les éléments de cette réflexion suivant trois axes : (i) un axe conceptuel considère les concepts majeurs et les axiomes du paradigme systémique ; (ii) leur pertinence pour la modélisation des fonctions biologiques est examinée dans le cadre d'un processus de signalisation intracellulaire ; (iii) une entrée opératoire, fondée sur cette réflexion méthodologique, illustre la cohérence apportée par un cadre théorique argumenté et l'utilisation de son formalisme pour la description et la représentation des activités biologiques. Ce formalisme conduit à interpréter le traitement des processus moléculaires en termes d'opérations organisationnelles produisant et transformant l'information génétique et à approfondir l'intelligibilité de la génération, de la circulation et du calcul de l'information dans la mise en place des organisations biologiques. Pour citer cet article : M. Roux-Rouquié, J.-L. Le Moigne, C. R. Biologies 325 (2002) 419-430. © 2002 Académies des sciences / Éditions scientifiques et médicales Elsevier SAS modélisation systémique / épistémologie / fonction biologique / organisation des connaissances / système d'information *Correspondence and reprints.

Ž . This paper presents the results of a combined empirical orthogonal function EOF analysis of Advanced Very High Ž . Ž . Ž . Resolution Radiometer AVHRR sea surface temperature SST data and sea-viewing wide field-of-view sensor SeaWiFS Ž . Ž chlorophyll concentration data over the Alboran Sea Western Mediterranean , covering a period of 1 year November . 1997-October 1998 . The aim of this study is to go beyond the limited temporal extent of available in situ measurements by inferring the temporal and spatial variability of the Alboran Gyre system from long temporal series of satellite observations, in order to gain insight on the interactions between the circulation and the biological activity in the system. In this context, EOF decomposition permits concise and synoptic representation of the effects of physical and biological phenomena traced by SST and chlorophyll concentration. Thus, it is possible to focus the analysis on the most significant phenomena and to understand better the complex interactions between physics and biology at the mesoscale. The results of the EOF analysis of AVHRR-SST and SeaWiFS-chlorophyll concentration data are presented and discussed in detail. These improve and complement the knowledge acquired during the in situ observational campaigns of the MAST-III Observations and Ž . Modelling of Eddy scale Geostrophic and Ageostrophic motion OMEGA Project. q

Interactions between bacteria and protozoa in soil were studied over 2-week periods in the field and in a pot experiment. Under natural conditions the total biological activity was temporarily synchronized by a large rainfall, and in the laboratory by the addition of water to dried-out soil, with or without plants. In the field, peaks in numbers and biomass of bacteria appeared after the rain, and a peak of naked amoebae quickly followed. Of the three investigated groups--flagellates, ciliates, and amoebae--only populations of the latter were large enough and fluctuated in a way that indicated a role as bacterial regulators. The bacterial increase was transient, and the amoebae alone were calculated to be able to cause 60% of the bacterial decrease. The same development of bacteria and protozoa was observed in the pot experiment: in the presence of roots, amoebic numbers increased 20 times and became 5 times higher than in the unplanted soil. In the planted pots, the amoebic increase was large enough to cause the whole bacterial decrease observed; but in the unplanted soil, consumption by the amoebae caused only one-third of the bacterial decrease.

There has been a rapid increase in the number and demand for approved biopharmaceuticals produced from animal cell culture processes over the last few years. In part, this has been due to the efficacy of several hu-manized monoclonal antibodies that are required at large ...

A new strategy for the skin delivery of bioactive compounds has been developed, using enzymes involved in the maintenance of the epidermal barrier function and the enzymatic transformation of corresponding precursors. This new strategy has been tested with regard to two enzymatic activities of the skin barrier: extracellular glucosidase and esterase/lipase. An analysis of the requirements for the glycosidic bond hydrolysis of any glycoconjugate by beta-glucocerebrosidase indicates that the release of the moiety linked to the glucose unit is obtained as long as the glycosidic bond being broken is not hindered, and as long as the leaving group property of the released moiety is good enough. This strategy was first applied to the release of the antioxidant delta-tocopherol. It was then extended to retinoic acid by introducing a spacer between the glucose unit and the bioactive moiety. This spacer was either a good leaving group such as hydroquinone, or a structure akin to a ceramide, n...

The process of desalting of a proline modelling solution by electrodialysis in five-and six-chamber electrodialysis apparatus was investigated. It has been shown that the process effectively proceeded in the six-chamber device. Changes of dry substances and pH of the proline modeling solution and also voltage in a circuit in the course of the desalting process were determined depending on the current density. Kinetic curves of migration of proline through a CМ-40 membrane in the desalting process have been registered and the optimum density of a current necessary to carry out the desalting process of proline solution has been determined. Kinetic curves of the proline solution desalting have shown that in optimal and close to optimal areas of current density 99.3%, desalting of the proline solution was achieved, while with a current higher than optimal the degree of desalting of solution was about 94.6%. It was shown that the obtained relationships of the desalting process of the proline modelling solution were completely reproduced in permeate desalting during the chalk-free L-proline, L-valine and L-alanine fermentations. On the basis of the obtained results, it is possible to develop technologically accessible electrodialysis of amino acids as well as other biologically active substance desalting from cultured liquids.

The widespread use of ␤-lactam antimicrobial agents as first-line therapy for the treatment of serious infections has led to the development of various resistances that have compromised the use of some agents. In certain countries, the lack of local or national surveillance programs limits the ability to detect these resistant strains and prevent their dissemination. A 10 medical center study in India was initiated to benchmark prevailing resistance rates for a range of bacterial pathogens to ␤-lactams, and it found high rates of ␤-lactamase-mediated resistance in Escherichia coli and Klebsiella spp. These rates included: cephalosporins (55.6-61.3% resistance), with extended-spectrum ␤-lactamase (ESBL) phenotypes noted in over 60% of E. coli isolates and in Salmonella spp. (3.2-8.1%). Imipenem, a carbapenem, was the only antimicrobial agent tested with 100% activity against Enterobacteriaceae. Cefpirome was the most active of the tested cephalosporins, and all were fully active against methicillin-susceptible staphylococci with the exception of ceftazidime. Molecular and susceptibility characterization of 52 selected ESBL-producing strains showed a high level of co-resistance with aminoglycosides and fluoroquinolones, and clonal dissemination of resistant strains within medical centers. Collaborative studies, such as those presented here, can accurately detect changes in resistance patterns, and their continued use may help limit the further development and spread of bacterial resistances in India.

The 14-membered heterocyclic 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetrazacyclotetradeca-7,14-diene, [(Me6[14]N4diene)], salts with structural formula of [(Me6[14]N4diene)]Br2(H2O)2), [(Me6[14]N4diene)Cl2])(H2O)3, Me6[14]N4diene.(ClO4)2, Me6[14]N4diene.(PF6)2 and Me6[14]N4diene.(NO3)2 have been synthesized without the necessity of a template. The salts were characterized by FTIR, and NMR spectroscopic techniques. X-ray study showed that the macrocyclic cation consists of a pair of protonated amines and azomethine nitrogen atoms located diagonally and opposite to each other. Only the macrocylic bromide and perchlorate salts showed activity against gram-positive E. faecalis and gram-negative E. Coli.

An examination of an organic extract of the cyanobacterium Lyngbya majuscula, collected from Wasini Island off the southern Kenyan coast, led to the isolation of the known cyclic depsipeptide antanapeptin A (1), recently isolated from a Madagascan collection of L. majuscula, and a new bioactive cyclic depsipeptide, homodolastatin 16 (2). The structures of these two compounds were determined from NMR and mass spectrometry data. Homodolastatin 16, a higher homologue of the potential anticancer agent dolastatin 16, exhibited moderate activity against oesophageal and cervical cancer cell lines. a 13 C NMR data for 5 acquired at 125 MHz; 1 H and 13 C NMR data for 2 acquired at 400 and 100 MHz, respectively. b Protons showing NOESY correlation with indicated proton(s). c Protons showing long-range correlation with indicated carbon.

A number of pyrimido[4,5-d]pyrimidine-2,5-dione derivatives were synthesized and screened for antibacterial and antifungal activities. All the synthesized compounds showed the potent antimicrobial activity. The quantitative structure-activity relationship investigation was applied to find a correlation between the different physicochemical parameters of the compounds studied and their biological activity.

Several acetyl-protected hydroxybenzyl diethyl phosphates (EHBPs) that are capable of forming quinone methide intermediates were synthesized and their cell growth inhibitory properties were evaluated in four different human cancer cell lines. Compounds 1, 1a, and 1b, corresponding to (4-acetyloxybenzyl diethylphosphate), (3-methyl-4-acetyloxybenzyl diethylphosphate), and (3-chloro-4-acetyloxybenzyl diethylphosphate), were significantly more potent than compounds 2 and 3, (2-acetyloxybenzyl diethylphosphate) and (3-acetyloxybenzyl diethylphosphate), respectively. Using HT-29 human colon cancer cells, compounds 1 and 3 increased apoptosis, inhibited proliferation, and caused a G 2 /M block in the cell cycle. Our data suggest that these compounds merit further investigation as potential anti-cancer agents.

Naltrexone (NTX) and fluoxetine (FLU) are useful for treating alcoholism and depression, respectively. Furthermore, these afflictions covary. Given the possibility that people might be prescribed NTX and FLU concurrently, we assessed the effects of these two agents on rats' pmpensityto drink an alcoholic beverage. Rats were given 65 days of access to a sweetened alcoholic beverage and water for 2 hr daily. At fitst, they took l i i ethanol, but after20 days, they took on average 20 to 2 5 g/kg of ethanol, daily during the 2-hr session. They also took sufficientw~tomaintaintheirhea~.After30days,theywemdivided into four groups to receive, 30 min before the drinking session, 1 of 4 different kinds of injections. For the next 20 days, one group received pbcebo daily. Another group received 5 mgkg of NTXdaily and another 5mgkg of FLU daily.Thefourth group received both 5 mgkg o f m and 5 mgkg of FLU daily. After #)days, the doses of NTXand FLU wem doubled acrossan additional10 days. Both NTXand FLU reduced rats' intake of alcoholic beverage. The combinatiorw of NTX and FLU, however,werenomOreeftechve ' in reducing rats' intake of alcoholic bev--than either alone. Also, the small dose of NTX seemed to lose its tbmedthecondusknthatsmalldOsesofNTXlose~effectiveness in suppressing intake of alcoholic bmmrage cross repeated adminisIrations. In summary, data provide 110 support forthe idea that FLU and NTX would act synergistically to reduce pmpemty to take alcohdic beverages.

Carotenoids are a group of phytochemicals that are recognized as playing an important role in the prevention of several degenerative diseases due to their antioxidant activity. The low water-solubility and poor photostability of β-carotene, a potentially important dietary antioxidant, prompted us to investigate β-carotene complexes able to increase its water solubility as well as its photostability in aqueous solution. In this work we have used humic acid in order to synthesize β-carotene–humic acid complexes in different ratios.Complexes were characterized by FT-IR and DSC. β-Carotene determination were performed by HPLC and antioxidant activity of β-carotene, humic acid and the complexes were determined by the TEAC method. The formulation β-carotene–humic acid 2:1 showed the highest photostability and water solubility. The antioxidant activity of the complexes was about 20 times lower than “free” β-carotene, suggesting a decreased chemical reactivity of the carotenoid in the complex. We showed that complexation of β-carotene with humic acids was able to increase its water solubility and photostability, and to affect the antioxidant activity of β-carotene after inclusion in HAs. This work provides a useful tool to avoid antioxidants photodegradation and oxidation by radicals, thus maintaining their biological activity.

J. M. Delaney and R. M. Wilkins. Toxicity of microcystin-LR, isolated from Microcystis aeruginosa, against various insect species. Toxicon 33, 771-778, 1995.-Microcystin-LR (MC-LR), isolated from the cyanobacterium Microcystis aeruginosa Kuetzing emend. Elenkin strain CCAP 1450/4 was tested for biological activity against four species of insect and the invertebrate Artemia salina. The efficacy of pesticidal activity was compared with various insecticides. The 24 hr LD,, value for third instar diamond-backed moth, Plutella xylostella, on ingestion from a treated leaf surface was 1 .O pg cm', compared with a 72 hr LD,, value for rotenone of 2..0 pg cm-*. The 24 hr LD, values of MC-LR and malathion on intrathoracic injection into adult house flies (Musca domestica) were 0.5 and 3.7 mg kg-l, respectively. MC-LR had no effect on M. domestica when applied topically at dosages up to 32 mg kg-'. MC-LR and malathion gave 24 hr LD, values of 4.7 and 13.1 mg kg-', respectively when injected into third instar cotton leafworm (Spodoptera littoralis). In fourth instar cabbage white butterfly larvae (Pieris brassicae) MC-LR injected gave 24 and 48 hr ~a,,, values of 3.9 and 1.9 mg kg-', respectively, whilst the 24 and 48 hr LD~ values for carbofuran were 0.4 and 0.3 mg kg-', respectively. An immersion bioassay with l-day-old brine shrimp larvae (Artemia salina) gave 24 hr LD,, values of 3.8 pgml-' for MC-LR and 1.8 pgrnl-' for carbofuran. MC-LR has appreciable insect toxicity, comparable to the three insecticides tested. The toxin look 24-48 hr to exert its full lethal effect in insects, much longer than the l-3 hr it takes in mammals. The potential use of MC-LR as an insecticide is discussed.

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Chronic renal failure is often associated with a resistance to the biologically active form of vitamin D 3 , the nuclear hormone 1␣,25-dihydroxyvitamin D 3 (VD). The actions of VD are mediated by the vitamin D receptor (VDR), a ligand-dependent transcription factor that binds as a dimeric complex with the retinoid X receptor (RXR) to specific DNA binding sites in the promoter regions of primary VD responding genes, referred to as VD response elements (VDREs). It could be shown in this study that uremic solutions derived from ultrafiltrate from hemodialysis patients and dialysate from peritoneal dialysis patients had an inhibitory effect on the complex formation and ligand inducibility of VDR-RXR heterodimers on different VDRE types. This inhibition was attributed to the formation of Schiff bases between ''reactive aldehydes'' and lysine residues of the DNA binding domain (DBD) of the VDR, but point mutagenesis data of different lysine residues in this study could not confirm this idea. However, the inhibitory effect of uremic solutions could also be observed for the complex formation of other homo-or heterodimer forming nuclear receptors, whereas an as a monomer binding nuclear receptor did not appear to be affected. These results indicate that VDR is a target of substances in uremic solutions in vitro, but also to some extent other nuclear receptors (i.e., other endocrine signaling systems) may be affected by renal failure.