Polyamines

This article is an extensive review of the literature on two component urethane systems that use water as a carrier. It generally covers the period from 1985 through 2000 with special emphasis on patent references since 1993. It includes both ambient temperature cured and baked systems containing unmodified and modified isocyanate building blocks. The main criterion for inclusion into this paper was that the finished urethane group containing polymer reaches its ultimate molecular weight after it is applied to a substrate, so that traditional latex-type materials are not emphasized.

Degradable polymer Biocompatibility a b s t r a c t The focus of this work was to develop potentially biodegradable, polycationic gene carriers possessing high efficiency for gene delivery and being essentially non-toxic. A library of 37 soluble polycations was synthesized by oligomerization of low molecular weight oligoamines with three different crosslinkers, dithiobis-succinimidyl proprionate, dimethyl dithiobis-propionamidate, and hexanediol diacrylate. The types of oligoamine and crosslinker influenced biophysical properties such as DNA binding, hemolytic and endosomolytic membrane activity, transfection efficiency and cytotoxicity of the gene carrier. Degradability of polymers based on reductive cleavage of disulfide bonds or ester hydrolysis was demonstrated. Within the library, oligoethylenimine (800 Da)-based polymers showed the highest gene transfer efficiencies and exceeded the golden standard linear polyethylenimine (22 kDa) in terms of activity/toxicity profile.

A sensitive and simple liquid chromatographic assay with fluorometric detection for unconjugated and acetylated polyantines in biological fluids is described. After precolumn derivatization with dansyl chloride, unconjugated polyamines and acetylated polyamines were extracted by elution from a Bond-Elut C,, column and then separated on a reversedphase column with gradient elution. The complete analysis of unconjugated putrescine, spermidine, and spermine in either hydrolyzed urine, cerebrospinal fluid or tissue could be accomplished within 20-26 min, while the simultaneous analysis of unconjugated poly-0378-4347/86/$03.50 0 1986 Elsevier Science Publishers B.V. 20 amines and monoacetylpolyamines could be completed within 40 min. Unhydrolyzed urine and cerebrospinal fluid required a Bond-EM cation-exchange clean-up before dansylation. Standard curves for the assay were linear up to 20 nmol/ml, and the within-day and day-today coefficients of variation were between 1.1 and 4.6% and between 1.6 and 11.8%, respectively. Results obtained with the method were compared with results obtained with a well established modified amino acid analyzer method for urine, tissue and cerebrospinal fluid samples. The correlation coefficients between these two methods were in the range 0.933-0.996. Detection limits between 50 and 150 fmol were achieved for unconjugated and acetylated polyamines. Of more than twenty drugs and amines tested for possible interference with the assay, only normetanephrine was found to have the same retention time as the internal standard 1,6-diaminohexane.

Potassium currents play a critical role in action potential repolarization, setting of the resting membrane potential, control of neuronal ®ring rates, and regulation of neurotransmitter release. The diversity of the potassium channels that generate these currents is nothing less than staggering. This diversity is generated by multiple genes (as many as 100 and perhaps more in some creatures) encoding the pore-forming channel a subunits, alternative splicing of channel gene transcripts, formation of heteromultimeric channels, participation of auxiliary (non-pore-forming) b and other subunits, and modulation of channel properties by post-translational modi®cations and other mechanisms. Prominent among the potassium channels are several families of calcium activated potassium channels, which are highly selective for potassium ions as their charge carrier, and require intracellular calcium for channel gating. The modulation of one of these families, that of the large conductance calcium activated and voltage-dependent potassium channels, has been especially widely studied. In this review we discuss a few selected examples of the modulation of these channels, to illustrate some of the molecular mechanisms and physiological consequences of ion channel modulation.

We have developed a technique for monitoring the internal calcium concentration-[Ca2+li-in a single selected cell in cerebellar slices of &day-old rats. In post-migratory granule cells NMDA induced a rapid, reversible and concentration-dependent increase in [Ca2+li ( + 22% at 10 /*M and + 210% at 100 PM). This effect was dependent on the presence of Ca2+ in the extracellular medium. When Mg'+ was absent from the perfusion buffer the sensitivity to NMDA was greatly increased (+ 108% at 10 PM). The NMDA response was not affected by glycine site agonists or by tetrodotoxin, a sodium channel blocker.

To evaluate the clinical complaints, laboratory data, treatment, and follow-up of patients with delayed adverse effects related to polyalkylimide implants (PAIs). Design: Prospective case series of patients injected with PAIs. Setting: A university tertiary teaching hospital. Patients: A prospectively acquired series of 25 patients with severe and/or persistent delayed adverse effects after PAI injection. The patients underwent clinical follow-up, a battery of blood tests, and when possible, biopsy and chest radiography. Main Outcome Measures: Clinical evaluation of granulomas, skin manifestations, and other local and sys-temic immune-mediated disorders possibly related to PAIs. Results: The average latency period for onset of symptoms was 13.4 months. Eight patients were previously injected with another implant. Tender inflammatory nodules were seen in 24 patients. Systemic or distant manifestations appeared in 6 cases. Laboratory abnormalities were found in 20 cases. After an average of 21.3 months of follow-up, 11 patients appeared to be free of adverse effects, and 10 still had recurrent bouts. Conclusion: Although infrequent, delayed and recurrent chronic inflammatory and granulomatous reactions may complicate PAI fillers.

The mechanisms that control polyamine (PA) metabolism in plant cell lines with different embryogenic potential are not well understood. This study involved the use of two Araucaria angustifolia cell lines, one of which was defined as being blocked, in that the cells were incapable of developing somatic embryos, and the other as being responsive, as it could generate somatic embryos. Cellular PA metabolism was modulated by using 5 mM arginine (Arg) or ornithine (Orn) at two time points during cell growth. Two days after subculturing with Arg, an increase in citrulline (Cit) content was observed, followed by a higher expression of genes related to PA catabolism in the responsive cell line; whereas, in the blocked cell line, we only observed an accumulation of PAs. After fourteen days, metabolism was directed towards putrescine accumulation in both cell lines. Exogenous Arg and Orn not only caused a change in cellular contents of PAs, but also altered the abundance of a broader spectru...

The development of polyamine transport inhibitors (PTIs), in combination with the polyamine biosynthesis inhibitor difluoromethylornithine (DFMO), provides a method to target cancers with high polyamine requirements. The DFMO+PTI combination therapy results in sustained intracellular polyamine depletion and cell death. A series of substituted benzene derivatives were evaluated for their ability to inhibit the import of spermidine in DFMO-treated Chinese hamster ovary (CHO) and L3.6pl human pancreatic cancer cells. Several design features were discovered which strongly influenced PTI potency, sensitivity to amine oxidases, and cytotoxicity. These included changes in (a) the number of polyamine chains appended to the ring system, (b) the polyamine sequence, (c) the attachment linkage of the polyamine to the aryl core, and (d) the presence of a terminal N-methyl group. Of the series tested, the optimal design was N 1 ,N 1 ′,N 1 ″-(benzene-1,3,5-triyltris(methylene))tris(N 4 -(4-(methylamino)butyl)butane-1,4-diamine, 6b, which contained three N-methylhomospermidine motifs. This PTI exhibited decreased sensitivity to amine oxidases and low toxicity as well as high potency (EC 50 = 1.4 μM) in inhibiting the uptake of spermidine (1 μM) in DFMOtreated L3.6pl human pancreatic cancer cells.

Amine oxidases (AOs) catalyse the oxidative de-amination of polyamines, ubiquitous polycationic compounds involved in important events of cell life. They include the copper-containing amine oxidases (CuAOs; EC 1.4.3.6) and the flavin-containing polyamine oxidases (PAOs; EC 1.5.3.11). The main physiological role of these moonlighting proteins has been linked to compartment-specific H 2 O 2 synthesis in different phases of development and differentiation as well as in the course of defence mechanisms against pathogens and abiotic stress. Moreover, several studies evidenced a correlation of AO expression levels with physiological stages characterized by intense metabolism, such as cell division or organ formation, thus leaving open the hypothesis that AOs may have also a role in the regulation of cell cycle through the modulation of polyamine cellular content. This update will deal with recent reports on the involvement of CuAOs and PAOs in abiotic (salt) stress, wound-healing and hostepathogen interactions.

Polyamines are ubiquitous molecules, which, like iron, are essential for cell growth. All eukaryotic cells are equipped with a specific polyamine transport system (PTS). Polyamines have primary and secondary amino groups which chelate bivalent metal cations such as Fe and Cu. In the present study, we investigated the potential contribution of naturally occurring polyamines and their active transport system to iron uptake. In presence of subtoxic Fe(III) (10 mM), treatment of CHO cells with spermine, and to a lesser extent with spermidine (10-100 mM), resulted in a marked cytotoxic effect. This cytotoxicity was prevented by the addition of an iron-chelator, deferioxamine, and was not observed in CHO-MG cells, a mutant cell line devoid of polyamine transport activity. Experiments using 14 C-polyamines and 55 Fe(III) revealed that these toxic effects were related to polyamine-modulation of iron uptake, and were dependent on the presence of the active PTS. These results demonstrated active uptake of polyamine-iron complexes via the PTS. The number of amino groups affected the efficacy of the studied natural polyamines to transport iron via the PTS. Spermine, a tetramine, was more efficient than the triamine spermidine. Co-transport of iron by the diamine putrescine was not observed. These results demonstrate that the cell polyamine transport system is a potential cell entry pathway for iron. The studied polyamines, spermine and spermidine, may be components of the pool of transferrin-independent iron-chelating vectors, which have recently attracted the attention of many investigators.

Quartz crystal microbalance with dissipation monitoring (QCM-D), atomic force microscopy (AFM) and field emission scanning electron microscopy (FESEM) were used as the tools to study the adsorption of bacteria onto surfaces of silica and polystyrene coated with materials related to papermaking. Cationic polyelectrolytes used as fixatives and retention aids in paper industry were found to promote irreversible adsorption of the ubiquitous white water bacterium, Pseudoxanthomonas taiwanensis, onto model surfaces of cellulose (pH 8). The high charged low molecular weight polyelectrolyte, poly(diallyldimethyl) ammonium chloride (pDADMAC) adsorbed to silica surface as a flat and rigid layer, whereas the low charged cationic polyacryl amide (C-PAM) of high molecular weight adsorbed as a thick and loose layer. AFM images showed that the polyelectrolytes accumulated as layers around each bacterial cell. In the presence of wood hemicellulose (O-acetyl-galactoglucomannan) the bacteria adsorbed massively, as large, tightly packed rafts (up to 0.05 mm in size) onto the polystyrene crystal surface coated with wood extractives (pH 4.7). AFM and FESEM micrographs also showed large naked areas (with no bacteria) in between the bacterial rafts on the crystal surface. In this case, QCM-D only incompletely responded to the massiveness of the bacterial adsorption. The results indicate that cationic polymers can be used to increase the retention of bacteria from the process water onto the fibre web and that, depending on the balance between hemicelluloses and wood extractives and pH of the process waters, bacteria can be drawn from process waters onto surfaces.

A linear, amphoteric poly(amidoamine) nicknamed AGMA1, based on 4-aminobutylguanidine, or agmatine, was successfully prepared by Michael-type polyaddition of monoprotonated agmatine and 2,2-bis(acrylamido)acetic acid (BAC). Copolymers between AGMA1 and the biocompatible poly(amidoamine) ISA23 (deriving from the polyaddition of 2-methylpiperazine with BAC) were also prepared. Acid-base titrations gave for AGMA1 three acid dissociation constants, with pK a values of 2.25, 7.45, and g12.1, corresponding to a strong acid, a mediumweak base, and a strong base, respectively. The charge distribution profiles show that this polymer is prevailingly cationic at all physiological pH values, the positive net average charge per unit varying from about 0.5 at pH 7.4 to about 1.0 at pH 5, with an isoelectric point at pH ≈ 10. Zeta-potential measurements confirmed this. Despite that, AGMA1 is nontoxic and nonhemolytic in vitro within all pH ranges tested (4-7.5). This is in contrast with the previously observed behavior of amphoteric PAAs, for instance ISA23, that are weakly hemolytic at pH 7.4 but highly hemolytic at pH 5÷5.5. The lack of hemolytic activity of AGMA1 even at acidic pH values seems typical of the agmatine-BAC sequences and may be ascribed to their RGD-like structure. In fact, AGMA1-ISA23 copolymers behave in a way increasingly similar to that of ISA23; that is, they become hemolytic at low pH values as their ISA23 content increases.

Polyamine flocculants were synthesized by the polycondensation of dimethylamine and epichlorohydrin, in which organic amines, e.g. 1,2diaminoethane, were used as modifying agents. Different products were obtained by varying the reaction parameters, such as the molar ratio of epichlorohydrin to dimethylamine, the amount of 1,2-diaminoethane and reaction temperature. The polyamine flocculants were characterized by transmission electron microscope (TEM). Their flocculation performance was evaluated with simulated dye liquor and actual printing and dyeing wastewater. The behavior of the flocculants was compared with that of inorganic coagulant, polyaluminum chloride (PAC). The experimental results show that polyamine with the highest viscosity and cationicity could be prepared under following conditions: an epichlorohydrin to dimethylamine molar ratio of 1.5, a reaction temperature of 70 • C, a 3% content of 1,2-diaminoethane in the total reaction monomers and a reaction time of 7 h. Polyamine polymers can, as flocculants for treating simulated and actual dye wastewater, remove color and COD efficiently. The rate of color removal from reactive red liquor, reactive blue liquor and reductive yellow liquor reached as high as 96%, 97% and 96%, respectively. The highest efficiency of color removal and COD removal from polyamine for treating dye wastewater was 90% and 89%, respectively.

The continued rise in obesity despite public education, awareness and policies indicates the need for mechanism-based therapeutic approaches to help control the disease. Our data, in conjunction with other studies, suggest an unexpected role for the polyamine catabolic enzyme spermidine/spermine-N1-acetyltransferase (SSAT) in fat homeostasis. Our previous studies showed that deletion of SSAT greatly exaggerates weight gain and that the transgenic overexpression suppresses weight gain in mice on a high-fat diet. This discovery is substantial but the underlying molecular linkages are only vaguely understood. Here, we used a comprehensive systems biology approach, on white adipose tissue (WAT), to discover that the partition of acetyl-CoA towards polyamine catabolism alters glucose homeostasis and hence, fat accumulation. Comparative proteomics and antibody-based expression studies of WAT in SSAT knockout, wild type and transgenic mice identified nine proteins with an increasing gradient across the genotypes, all of which correlate with acetyl-CoA consumption in polyamine acetylation. Adipose-specific SSAT knockout mice and global SSAT knockout mice on a high-fat diet exhibited similar growth curves and proteomic patterns in their WAT, confirming that attenuated consumption of acetyl-CoA in acetylation of polyamines in adipose tissue drives the obese phenotype of these mice. Analysis of protein expression indicated that the identified changes in the levels of proteins regulating acetyl-CoA consumption occur via the AMP-activated protein kinase pathway. Together, our data suggest that differential expression of SSAT markedly alters acetyl-CoA levels, which in turn trigger a global shift in glucose metabolism in adipose tissue, thus affecting the accumulation of body fat.

We evaluated phytohormone and polyamine biosynthesis, siderophore production, and phosphate solubilization in two strains (Cd and Az39) of Azospirillum brasilense used for inoculant formulation in Argentina during the last 20 years. Siderophore production and phosphate solubilization were evaluated in a chemically defined medium, with negative results. Indole 3-acetic acid (IAA), gibberellic acid (GA 3 ), and abscisic acid (ABA) production were analyzed by gas chromatography-mass spectrometry. Ethylene, polyamine, and zeatin (Z) biosynthesis were determined by gas chromatography-flame ionization detector and high performance liquid chromatography (HPLC-fluorescence and -UV), respectively. Phytohormones IAA, Z, GA 3 , ABA, ethylene, and growth regulators putrescine, spermine, spermidine, and cadaverine (CAD) were found in culture supernatant of both strains. IAA, Z, and GA 3 were found in all two strains; however, their levels were significantly higher (p<0.01) in Cd (10.8, 2.32, 0.66 μg ml −1 ). ABA biosynthesis was significantly higher (p<0.01) in Az39 (0.077 μg ml −1 ). Ethylene and polyamine CAD were found in all two strains, with highest production in Cd cultured in NFb plus L-methionine (3.94 ng ml −1 h −1 ) and Az39 cultured in NFb plus L-lysine (36.55 ng ml −1 h −1 ). This is the first report on the evaluation of important bioactive molecules in strains of A. brasilense as potentially capable of direct plant growth promotion or agronomic yield increase. Az39 and Cd showed differential capability to produce the five major phytohormones and CAD in chemically defined medium. This fact has important technological implications for inoculant formulation as different concentrations of growth regulators are produced by different strains or culture conditions.

Dendritic nanomaterials are emerging as key building blocks for a variety of nanoscale materials and technologies. Poly(amidoamine) (PAMAM) dendrimers were the first class of dendritic nanomaterials to be commercialized. Despite numerous investigations, the environmental fate, transport, and toxicity of PAMAM dendrimers is still not well understood. As a first step toward the characterization of the environmental behavior of dendrimers in aquatic systems, we measured the octanol-water partition coefficients (logK ow ) of a homologous series of PAMAM dendrimers as a function of dendrimer generation (size), terminal group and core chemistry. We find that the logK ow of PAMAM dendrimers depend primarily on their size and terminal group chemistry. For G1-G5 PAMAM dendrimers with terminal NH 2 groups, the negative values of their logK ow indicate that they prefer to remain in the water phase. Conversely, the formation of stable emulsions at the octanol-water (O/ W) interface in the presence of G6-NH 2 and G8-NH 2 PAMAM dendrimers suggest they prefer to partition at the O/W interface. In all cases, published studies of the cytotoxicity of Gx-NH 2 PAMAM dendrimers show they strongly interact with the lipid bilayers of cells. These results suggest that the logK ow of a PAMAM dendrimer may not be a good predictor of its affinity with natural organic media such as the lipid bilayers of cell membranes. * Corresponding author phone: 626 395 2730; fax: 626 585 0918.

Due to its low digestibility in the small intestine, a major fraction of the polyol isomalt reaches the colon. However, little is known about effects on the intestinal microflora. During two 4-week periods in a double-blind, placebo-controlled, cross-over design, nineteen healthy volunteers consumed a controlled basal diet enriched with either 30 g isomalt or 30 g sucrose daily. Stools were collected at the end of each test phase and various microbiological and luminal markers were analysed. Fermentation characteristics of isomalt were also investigated in vitro. Microbiological analyses of faecal samples indicated a shift of the gut flora towards an increase of bifidobacteria following consumption of the isomalt diet compared with the sucrose diet (P, 0·05). During the isomalt phase, the activity of bacterial b-glucosidase decreased (P, 0·05) whereas b-glucuronidase, sulfatase, nitroreductase and urease remained unchanged. Faecal polyamines were not different between test periods with the exception of cadaverine, which showed a trend towards a lower concentration following isomalt (P¼0·055). Faecal SCFA, lactate, bile acids, neutral sterols, N, NH 3 , phenol and p-cresol were not affected by isomalt consumption. In vitro, isomalt was metabolized in several bifidobacteria strains and yielded high butyrate concentrations. Isomalt, which is used widely as a low-glycaemic and low-energy sweetener, has to be considered a prebiotic carbohydrate that might contribute to a healthy luminal environment of the colonic mucosa.

The aim of the study was to prepare cationic ISCOMs using cationic derivatives of the saponin Quil A. The polyamines ethylenediamine, spermidine and spermine were conjugated with the glucuronic acid moiety of Quil A. The aqueous solubility of the derivatives increased with decreasing pH, and the pK a values were between 6 and 7. The CMCs of the ionised derivatives were around 0.5-1.0 mg/mL. Using the method of hydration of freeze-dried monophase systems, the interaction of each of the Quil A derivatives with phosphatidylcholine and cholesterol, at a mass ratio of 4:4:2 and a pH of 3 and 7.4, was investigated. A few ISCOM-like structures were present in the systems prepared at pH 7.4, hence the ternary system of Quil A spermine derivative, phosphatidylcholine and cholesterol was further investigated at pH 7.4 using a variety of mass ratios. A relatively high number of cationic ISCOM-like structures were observed at the mass ratio of 6:2:2. These ISCOM-like structures were less homogeneous and more irregular in shape than ISCOMs prepared from unmodified Quil A. Colloidal particles with positive zeta potential were produced and may find application in the delivery of nucleic acids or anionic proteins.

Polyamines play a critical role in the development of intestinal and immune systems during the infant breastfeeding period, but the effect of polyamines on the microbiota has not been reported. The aim of our study was to characterize the impact on the colonization pattern in neonatal BALB/cOlaHsd mice after supplementing an infant formula (IF) with a mixture of putrescine (PUT), spermidine (SPD) and spermine (SPM). A total of 48 pups (14 days old) were randomly assigned to 4-day intervention groups as follows: breast-fed (unweaned) pups (n=12); weaned pups (n=12) fed an infant formula (IF); weaned pups (n=12) fed an IF enriched with a low concentration of PUT, SPD and SPM (2.10, 22.05 and 38.00 μg/day, respectively); and weaned pups (n=12) fed with IF enriched with a high concentration of PUT, SPD and SPM (8.40, 88.20 and 152.00 μg/day, respectively) of polyamines in accordance with normal proportions found in human milk. Microbiota composition was analyzed by fluorescent in situ hybridization (FISH) with flow cytometry detection. Microbiota changes in formula-fed mice were significantly greater following supplementation with polyamines (Pb.01). Bifidobacterium group bacteria, Akkermansia-like bacteria and Lactobacillus-Enterococcus group levels were higher in the groups fed infant formula supplemented with polyamines, resulting in even higher numbers of bacteria than in the breastfed pups. Our findings indicate that infant formulas enriched with polyamines may interact with gut microbiota, suggesting that further studies in human infants are required to assess the impact of polyamines on both growth and microbiota levels.

Polyamine metabolism is intimately linked to the physiological state of the cell. Low polyamines levels promote growth cessation, while increased concentrations are often associated with rapid proliferation or cancer. Delicately balanced biosynthesis, catabolism, uptake and excretion are very important for maintaining the intracellular polyamine homeostasis, and deregulated polyamine metabolism is associated with imbalanced metabolic red/ox state. Although many cellular targets of polyamines have been described, the precise molecular mechanisms in these interactions are largely unknown. Polyamines are readily interconvertible which complicate studies on the functions of the individual polyamines. Thus, non-metabolizable polyamine analogues, like carbon-methylated analogues, are needed to circumvent that problem. This review focuses on methylated putrescine, spermidine and spermine analogues in which at least one hydrogen atom attached to polyamine carbon backbone has been replaced by a methyl group. These analogues allow the regulation of both metabolic and catabolic fates of the parent molecule. Substituting the natural polyamines with methylated analogue(s) offers means to study either the functions of an individual polyamine or the effects of altered polyamine metabolism on cell physiology. In general, gem-dimethylated analogues are considered to be non-metabolizable by polyamine catabolizing enzymes spermidine/spermine-N 1acetyltransferase and acetylpolyamine oxidase and they support short-term cellular proliferation in many experimental models. Monomethylation renders the analogues chiral, offering some advantage over gem-dimethylated analogues in the specific regulation of polyamine metabolism. Thus, methylated polyamine analogues are practical tools to meet existing biological challenges in solving the physiological functions of polyamines.

The present review reports on the main characteristics and properties of plants cultivated following organic and conventional procedures, in the attempt to clarify give a deeper insight into some possible differences and to compare the two cultivation procedures. Here, we summarise research results regarding nutritional and safety properties of vegetable foods, evidencing qualitative differences observed between the two cultivation methods. It appears that the intake of organic foods leads to some advantages, such as the ingestion of a higher content of phenolic compounds and some vitamins, such as vitamin C, and a lower content of nitrates and pesticides. From literature, it appears that a special care should be taken about the ingestion of foods in relation to the content of some substances, e.g. polyamines, substances stimulating cellular division, because some foods coming from organic origin present a higher content of these compounds, which could explain some of the effect of the diet on patients affected by certain syndromes.

The surface charge of a biomaterial represents a promising tool to direct cellular behavior, which is crucial for therapeutic approaches in regenerative medicine. To expand the understanding of how the material surface charge affects protein adsorption and mesenchymal stem cell behavior, differently charged surfaces with zeta potentials spanning from -25 mV to +15 mV were fabricated by the conjugation of poly(amidoamine) to alginate-based hydrogels. We showed that the increase of the biomaterials surface charge resulted in enhanced quantities of biologically available, surface-attached proteins. Since different surface charges were equalized after protein adsorption, mesenchymal stem cells interacted rather with diverse protein compositions instead of different surface features. Besides an enhanced cell attachment to increasingly positively charged surfaces, the cell spreading area and the expression of adhesion-related genes integrin α5 and tensin 1 were found to be increased after...

Ficus carica Linn. (Moraceae) is commonly known as edible fig. The leaves, roots, fruits and latex of the plant are medicinally used in different diseases. The leaves are claimed to be effective in various inflammatory conditions like painful or swollen piles, insect sting and bites. However, there has been no report on anti-inflammatory and antioxidant activity of F. carica leaves. Therefore the aim of this study was to evaluate the anti-inflammatory and antioxidant activity of F. carica leaves. Our study validated the traditional claim with pharmacological data. Anti-inflammatory and antioxidant activity of the drug could be due to the presence of steroids and flavanoids, respectively, which are reported to be present in the drug. Furthermore, the anti-inflammatory activity of the drug could be due to its free radical scavenging activity. Further work is also required to isolate and characterise the active constituents responsible for the anti-inflammatory activities.

This is a short review of the classical and new, natural and synthetic plant hormones and growth regulators (phytohormones) and highlights some of their uses in plant tissue culture. Plant hormones rarely act alone, and for most processes-at least those that are observed at the organ level--many of these regulators have interacted in order to produce the final effect. The following substances are discussed: (a) Classical plant hormones (auxins, cytokinins, gibberellins, abscisic acid, ethylene) and growth regulatory substances with similar biological effects. New, naturally occurring substances in these categories are still being discovered. At the same time, novel structurally related compounds are constantly being synthesized. There are also many new but chemically unrelated compounds with similar hormone-like activity being produced. A better knowledge of the uptake, transport, metabolism, and mode of action of phytohormones and the appearance of chemicals that inhibit synthesis, transport, and action of the native plant hormones has increased our knowledge of the role of these hormones in growth and development. (b) More recently discovered natural growth substances that have phytohormonal-like regulatory roles (polyamines, oligosaccharins, salicylates, jasmonates, sterols, brassinosteroids, dehydrodiconiferyl alcohol glucosides, turgorins, systemin, unrelated natural stimulators and inhibitors), as well as myoinositol. Many of these growth active substances have not yet been examined in relation to growth and organized development in vitro.

A reversed phase ion-pair liquid chromatographic method for the determination of nicotine in commercial tobacco products was previously developed and optimized Ciolino, L. A.; Turner, J. A.; McCauley, H. A.; Smallwood, A. W.; Yi, T. Y. J. Chromatogr. 1999a, 852 (2), 451-463) and provided reliable results for the determination of nicotine in commercial moist snuff (Ciolino, L. A.; McCauley, H. A.; Fraser, D. B.; Barnett, D. Y.; Yi, T. Y.; Turner, J. A. J. Agric. Food Chem. 1999b, 47, 3706-3712). The method uses an aqueous-based sample extraction and provides rapid separation of nicotine from the minor tobacco alkaloids and other commercial tobacco components. In the present work, the method is evaluated for the determination of nicotine in commercial cigarettes and compared to both an official AOAC method for total alkaloids in tobacco (AOAC, AOAC Official Methods of Analysis of AOAC International, 16th ed.; AOAC International: Gaithersburg, MD, 1995; pp 30-31), and a published GC method Greene, G. H. Beitr. Tabakforsch. 1976, 8 (6), 359-361). Good agreement was obtained between the ion-pair LC method and the GC method with relative differences in determined nicotine contents of 0.6 to 5% for a series of commercial and reference cigarettes.

A low molecular weight ribonuelease (M, 18000) was isolated and purified from human uremic serum, as determined by Sephadex gel filtration and SDS-polyacrylamide gel electrophoresis. Its relationship to the human urinary ribonuclease (/14, 33 000) is investigated in the following paper.

Polyamines play important roles in diverse plant growth and development processes, including seed germination, tissue lignifi cation, organogenesis, fl owering, pollination, embryogenesis, fruit development, ripening, abscission, senescence, and stress responses. In all these processes, synergistic and antagonistic interactions among various plant hormones have been shown. Although signifi cant progress has been made in understanding the regulation of biosynthesis and signal transduction mechanisms for most of the plant hormones, inroads into the molecular mechanisms underlying polyamine (PA) action have just begun. Little is known or understood about the signal transduction pathways regulating a myriad of PA effects. We, therefore, embarked on evaluating and collating the information on changes in the transcriptome based on metabolic engineering of the PA pathway as well as mutants of PA biosynthesis. Also taken into consideration are the studies using exogenous application of PAs. Our analysis has revealed complex and differential relationships among the three main PAs-putrescine, spermidine and spermine-in regard to regulation of plant hormone biosynthesis and signaling. Putrescine was positively linked to the expression of genes regulating ABA biosynthesis but downregulated those of ethylene, jasmonates, and gibberellin biosynthesis, and the action of spermidine was found to be exactly opposite. Spermine, on the other hand, enhanced genes for ethylene and jasmonates biosynthesis but downregulated those for gibberellins and abscisic acid biosynthesis. In regard to hormone signaling pathways, spermidine positively regulated salicylic acid signaling genes, and those of auxin and cytokinins signaling genes were linked to spermine action. Putrescine was neutral to positive in regulating jasmonates signaling. PAs seem to be neutral in regard to brassinosteroids biosynthesis or signaling pathways.

Huntington hastalığı, istemsiz koreik hareketler, bilişsel kayıplar ve psikolojik bozukluklarla karakterize edilen, otozomal dominant geçişli, geç başlangıçlı ve ölümcül bir hastalıktır. Hastalığa sebep olan mutasyon, IT-15 geninin birinci ek sonunda tekrar eden CAG bazlarının sayılarındaki artıştır. Mutant genin ifadesi, striyatal gam ma amino bütirik asit ile ten (GA BA-er jik) orta boy dikensi nö ronların seçimli ölümüne neden olur. Mutant huntingtin (htt) proteininin konformasyonu,
pro te in yı kı mı ve übi kü tin-pro te o zom sis te mi (UPS), gen ya zı lı mı dü zen le me le rin de ki de ği şim ler
ve ek si to tok si si te, nö ro de je ne ras yo nun mo le kü ler me ka niz ma la rı ara sın da dır. Uya rı cı kim ya sal la -
rın aşı rı mik ta rı hüc re le ri sü rek li uya ra rak has sas hüc re le rin ek si to tok sik ölüm le ri ne se bep olur lar.
Glu ta mat da ba zal gang li ya dan sa lı nan uya rı cı nö rot rans mi ter ler den bi ri dir. Hun ting ton has ta lı -
ğın da stri ya tal nö ron la rın kay be dil me si glu ta mat re sep tö rü ara cı lı ek si to tok si si te nin pa to ge nez de etki
li ola bi le ce ği ne işa ret eder. İyo not ro fik glu ta mat re sep tör le ri (iG luR) ara sın dan bi ri olan
N-me til-D-As par tat re sep tör le ri (NMDAR)’nin uya rıl ma sı ve bu nu ta ki ben nük le er fak tör kap pa B
(NF ± B) ya zı lım fak tö rü nün ak ti vas yo nu nö ro nal ölüm ile so nuç la nır. NMDAR, glu ta mat bağ lan -
ma böl ge le ri ne ek ola rak po li a min bağ lan ma böl ge le ri de içe rir. Po li a min le rin mu tant htt pro te i -
ni nin, NMDAR ve NF ± B ya zı lım fak tö rü ile ay rı ay rı iliş ki içe ri sin de ol ma sı, bu pro te i nin,
Hun ting ton has ta lı ğın da mey da na ge len nö ro de je ne ras yon da mer ke zi bir rol oy na ya bi le ce ği ni düşün
dür mek te dir. Bu ne den le, Hun ting ton has ta lı ğın da po li a min me ta bo liz ma sı nın de tay lı araş tırıl ma sı ve an la şıl ma sı has ta lı ğın te da vi sin de ye ni yak la şım lar üre til me si ni sağ la ya cak tır.

Classically, polyamines is a family of molecules (i.e. putrescine, spermine, spermidine) derived from ornithine according to a decarboxylation/ condensative process. More recently, it has been demonstrated that arginine can be metabolised according to the same pathway leading to agmatine formation. Polyamines are essential for the growth, the maintenance and the function of normal cells. The complexity of their metabolism and the fact that polyamines homeostasis is tightly regulated support the idea that polyamines are essential to cell survival. Multiple abnormalities in the control of polyamines metabolism might be implicated in several pathological processes. This paper summarises the knowledge about polyamines metabolism and point out the importance of these molecules as a target for the development of therapeutic tools and nutritional strategy.

The experimental and theoretical methods of determination of gas-phase basicities, proton affinities and protonation entropies are presented in a tutorial form. Particularities and limitations of these methods when applied to polyfunctional molecules are emphasized. Structural effects during the protonation process in the gas-phase and their consequences on the corresponding thermochemistry are reviewed and classified. The role of the nature of the basic site (protonation on non-bonded electron pairs or on p-electron systems) and of substituent effects (electrostatic and resonance) are first examined. Then, linear correlations observed between gas-phase basicities and ionization energies or substituent constants are recalled. Hydrogen bonding plays a special part in proton transfer reactions and in the protonation characteristics of polyfunctional molecules. A survey of the main properties of intermolecular and intramolecular hydrogen bonding in both neutral and protonated species is proposed. Consequences on the protonation thermochemistry, particularly of polyfunctional molecules are discussed. Finally, chemical reactions which may potentially occur inside protonated clusters during the measurement of gas-phase basicities or inside a protonated polyfunctional molecule is examined. Examples of bond dissociations with hydride or alkyl migrations, proton transport catalysis, tautomerization, cyclization, ring opening and nucleophilic substitution are presented to illustrate the potentially complex chemistry that may accompany the protonation of polyfunctional molecules. # 2007 Wiley Periodicals, Inc., Mass Spec Rev 26:775-835, 2007

Polyamines are essential cell constituents for all organisms. The present review highlights important differences in the synthesis, degradation, and interconversion of polyamines between the protozoan parasites (Trypanosoma brucei, Trypanosoma cruzi, Cryptosporidium parvum and Trichomonas vaginalis) and their mammalian hosts. Approaches include development of mono-and di-substituted polyamine analogs targeting polyamine interconversion, as well as more traditional targeting of synthetic enzymes and related pathways.

Amine oxidases (AOs) catalyse the oxidative de-amination of polyamines, ubiquitous polycationic compounds involved in important events of cell life. They include the copper-containing amine oxidases (CuAOs; EC 1.4.3.6) and the flavin-containing polyamine oxidases (PAOs; EC 1.5.3.11). The main physiological role of these moonlighting proteins has been linked to compartment-specific H 2 O 2 synthesis in different phases of development and differentiation as well as in the course of defence mechanisms against pathogens and abiotic stress. Moreover, several studies evidenced a correlation of AO expression levels with physiological stages characterized by intense metabolism, such as cell division or organ formation, thus leaving open the hypothesis that AOs may have also a role in the regulation of cell cycle through the modulation of polyamine cellular content. This update will deal with recent reports on the involvement of CuAOs and PAOs in abiotic (salt) stress, wound-healing and hostepathogen interactions.

Polyamines are ubiquitous molecules, which, like iron, are essential for cell growth. All eukaryotic cells are equipped with a specific polyamine transport system (PTS). Polyamines have primary and secondary amino groups which chelate bivalent metal cations such as Fe and Cu. In the present study, we investigated the potential contribution of naturally occurring polyamines and their active transport system to iron uptake. In presence of subtoxic Fe(III) (10 mM), treatment of CHO cells with spermine, and to a lesser extent with spermidine (10-100 mM), resulted in a marked cytotoxic effect. This cytotoxicity was prevented by the addition of an iron-chelator, deferioxamine, and was not observed in CHO-MG cells, a mutant cell line devoid of polyamine transport activity. Experiments using 14 C-polyamines and 55 Fe(III) revealed that these toxic effects were related to polyamine-modulation of iron uptake, and were dependent on the presence of the active PTS. These results demonstrated active uptake of polyamine-iron complexes via the PTS. The number of amino groups affected the efficacy of the studied natural polyamines to transport iron via the PTS. Spermine, a tetramine, was more efficient than the triamine spermidine. Co-transport of iron by the diamine putrescine was not observed. These results demonstrate that the cell polyamine transport system is a potential cell entry pathway for iron. The studied polyamines, spermine and spermidine, may be components of the pool of transferrin-independent iron-chelating vectors, which have recently attracted the attention of many investigators.

Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD) is a neurodegenerative disorder with progressive memory loss. It has been shown that the cholinergic neurotransmission deficit is one of the neurochemical characteristics of AD, and that L-arginine and its metabolites also play a prominent role in AD pathogenesis. Scopolamine, a non-selective muscarinic receptor antagonist, blocks cholinergic neurotransmission and impairs behavioural function, including learning and memory. This study investigated the effects of scopolamine on animals&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; behavioural performance and L-arginine metabolism in the hippocampus and prefrontal cortex. Rats were given intraperitoneal injections of scopolamine (0.8 mg/kg) or saline (1 ml/kg) and tested in the Y-maze, open field, water maze and elevated plus maze 30 min post-treatment. After completion of the behavioural testing, the CA1, CA2/3 and dentate gyrus (DG) sub-regions of the hippocampus and the prefrontal cortex were harvested to measure the activity and protein expression of nitric oxide synthase (NOS) and arginase, and the levels of L-arginine, L-citrulline, L-ornithine, agmatine, putrescine, spermidine, spermine, glutamate and GABA. Scopolamine treated rats displayed reduced alternation and exploratory behaviour, increased swimming speed and impaired spatial learning and memory. There were significantly decreased NOS activity, increased arginase activity, and increased L-ornithine and putrescine levels in the DG, but not other regions examined, in the scopolamine treated rats as compared to the controls. These findings suggest that scopolamine impairs behavioural function and alters L-arginine metabolism in the DG sub-region of the hippocampus specifically. The underlying mechanisms of it remain to be explored further.

IAA Plant growth promotion Rice endophyte Rice epiphyte Yeast a b s t r a c t A total of 1035 yeast isolates, obtained from rice and sugar cane leaves, were screened primarily for indole-3-acetic acid (IAA) production. Thirteen isolates were selected, due to their IAA production ranging from 1.2 to 29.3 mg g À1 DCW. These isolates were investigated for their capabilities of calcium phosphate and ZnO 3 solubilisation, and also for production of NH 3 , polyamine, and siderophore. Their 1-aminocyclopropane-1-carboxylate (ACC) deaminase, catalase and fungal cell wall-degrading enzyme activities were assessed. Their antagonism against rice fungal pathogens was also evaluated. Strain identification, based on molecular taxonomy, of the thirteen yeast isolates revealed that four yeast species e i.e. Hannaella sinensis (DMKU-RP45), Cryptococcus flavus (DMKU-RE12, DMKU-RE19, DMKU-RE67, and DMKU-RP128), Rhodosporidium paludigenum (DMKU-RP301) and Torulaspora globosa (DMKU-RP31) e were capable of high IAA production. Catalase activity was detected in all yeast strains tested. The yeast R. paludigenum DMKU-RP301 was the best IAA producer, yielding 29.3 mg g À1 DCW, and showed the ability to produce NH 3 and siderophore. Different levels of IAA production (7.2e9.7 mg g À1 DCW) were found in four strains of C. flavus DMKU-RE12, DMKU-RE19, and DMKU-RE67, which are rice leaf endophytes, and strain DMKU-RP128, which is a rice leaf epiphyte. NH 3 production and carboxymethyl cellulase (CMCase) activity was also detected in these four strains. Antagonism to fungal plant pathogens and production of antifungal volatile compounds were exhibited in T. globosa DMKU-RP31, as well as a moderate level of IAA production (4.9 mg g À1 DCW). The overall results indicated that T. globosa DMKU-RP31 might be used in two ways: enhancing plant growth and acting as a biocontrol agent. In addition, four C. flavus were also found to be strains of interest for optimal IAA production. ª

This is a short review of the classical and new, natural and synthetic plant hormones and growth regulators (phytohormones) and highlights some of their uses in plant tissue culture. Plant hormones rarely act alone, and for most processes-at least those that are observed at the organ level--many of these regulators have interacted in order to produce the final effect. The following substances are discussed: (a) Classical plant hormones (auxins, cytokinins, gibberellins, abscisic acid, ethylene) and growth regulatory substances with similar biological effects. New, naturally occurring substances in these categories are still being discovered. At the same time, novel structurally related compounds are constantly being synthesized. There are also many new but chemically unrelated compounds with similar hormone-like activity being produced. A better knowledge of the uptake, transport, metabolism, and mode of action of phytohormones and the appearance of chemicals that inhibit synthesis, transport, and action of the native plant hormones has increased our knowledge of the role of these hormones in growth and development. (b) More recently discovered natural growth substances that have phytohormonal-like regulatory roles (polyamines, oligosaccharins, salicylates, jasmonates, sterols, brassinosteroids, dehydrodiconiferyl alcohol glucosides, turgorins, systemin, unrelated natural stimulators and inhibitors), as well as myoinositol. Many of these growth active substances have not yet been examined in relation to growth and organized development in vitro.

Ionic ligands can bind to polyelectrolytes such as DNA or charged polysaccharides. We develop a Poisson-Boltzmann treatment to compute binding constants as a function of ligand charge and salt concentration in the limit of low ligand concentration. For flexible chain ligands, such as oligopeptides, we treat their conformations using lattice statistics.