Ornamental plants on sale to the public are a significant source of pesticide residues with implications for the health of pollinating insects.

Garden centres frequently market nectar- and pollen-rich ornamental plants as "pollinator-friendly", however these plants are often treated with pesticides during their production. There is little information on the nature of pesticide residues present at the point of purchase and whether these plants may actually pose a threat to, rather than benefit, the health of pollinating insects. Using mass spectrometry analyses, this study screened leaves from 29 different 'bee-friendly' plants for 8 insecticides and 16 fungicides commonly used in ornamental production. Only two plants (a Narcissus and a Salvia variety) did not contain any pesticide and 23 plants contained more than one pesticide, with some species containing mixtures of 7 (Ageratum houstonianum) and 10 (Erica carnea) different agrochemicals. Neonicotinoid insecticides were detected in more than 70% of the analysed plants, and chlorpyrifos and pyrethroid insecticides were found in 10% and 7% of plants respectively. Boscalid, spiroxamine and DMI-fungicides were detected in 40% of plants. Pollen samples collected from 18 different plants contained a total of 13 different pesticides. Systemic compounds were detected in pollen samples at similar concentrations to those in leaves. However, some contact (chlorpyrifos) and localised penetrant pesticides (iprodione, pyroclastrobin and prochloraz) were also detected in pollen, likely arising from direct contamination during spraying. The neonicotinoids thiamethoxam, clothianidin and imidacloprid and the organophosphate chlorpyrifos were present in pollen at concentrations between 6.9 and 81 ng/g and at levels that overlap with those known to cause harm to bees. The net effect on pollinators of buying plants that are a rich source of forage for them but simultaneously risk exposing them to a cocktail of pesticides is not clear. Gardeners who wish to gain the benefits without the risks should seek uncontaminated plants by growing their own from seed, plant-swapping or by buying plants from an organic nursery.

Topical application of LEVORAG® as first-line treatment for chronic anal fissures: a preliminary multicentric study.

AIM: The aim of the present study was to assess the safety and efficacy of this new topical agent as a first line treatment in patients with chronic anal fissures. METHODS: Nine centres were involved in the study. Patients with chronic anal fissures were recruited and received Levorag® for 40 days. Follow-up visits were conducted at 10, 20 and 40 days from the recruitment. Primary outcome was the healing rate, secondary outcome the reduction of pain at the end of the treatment measured with a VAS scale. RESULTS: Fifty patients completed the treatment. No adverse events were recorded. 60% of patients healed completely at the end of the treatment. In those that did not heal the reduction of mean VAS values was 60%. CONCLUSION: The use of Levorag® on patients affected by chronic anal fissures achieved in the short term results similar to those experienced by more classic local treatments without any side effect.

Systemic insecticides (neonicotinoids and fipronil): trends, uses, mode of action and metabolites.

Since their discovery in the late 1980s, neonicotinoid pesticides have become the most widely used class of insecticides worldwide, with large-scale applications ranging from plant protection (crops, vegetables, fruits), veterinary products, and biocides to invertebrate pest control in fish farming. In this review, we address the phenyl-pyrazole fipronil together with neonicotinoids because of similarities in their toxicity, physicochemical profiles, and presence in the environment. Neonicotinoids and fipronil currently account for approximately one third of the world insecticide market; the annual world production of the archetype neonicotinoid, imidacloprid, was estimated to be ca. 20,000 tonnes active substance in 2010. There were several reasons for the initial success of neonicotinoids and fipronil: (1) there was no known pesticide resistance in target pests, mainly because of their recent development, (2) their physicochemical properties included many advantages over previous generations of insecticides (i.e., organophosphates, carbamates, pyrethroids, etc.), and (3) they shared an assumed reduced operator and consumer risk. Due to their systemic nature, they are taken up by the roots or leaves and translocated to all parts of the plant, which, in turn, makes them effectively toxic to herbivorous insects. The toxicity persists for a variable period of time-depending on the plant, its growth stage, and the amount of pesticide applied. A wide variety of applications are available, including the most common prophylactic non-Good Agricultural Practices (GAP) application by seed coating. As a result of their extensive use and physicochemical properties, these substances can be found in all environmental compartments including soil, water, and air. Neonicotinoids and fipronil operate by disrupting neural transmission in the central nervous system of invertebrates. Neonicotinoids mimic the action of neurotransmitters, while fipronil inhibits neuronal receptors. In doing so, they continuously stimulate neurons leading ultimately to death of target invertebrates. Like virtually all insecticides, they can also have lethal and sublethal impacts on non-target organisms, including insect predators and vertebrates. Furthermore, a range of synergistic effects with other stressors have been documented. Here, we review extensively their metabolic pathways, showing how they form both compound-specific and common metabolites which can themselves be toxic. These may result in prolonged toxicity. Considering their wide commercial expansion, mode of action, the systemic properties in plants, persistence and environmental fate, coupled with limited information about the toxicity profiles of these compounds and their metabolites, neonicotinoids and fipronil may entail significant risks to the environment. A global evaluation of the potential collateral effects of their use is therefore timely. The present paper and subsequent chapters in this review of the global literature explore these risks and show a growing body of evidence that persistent, low concentrations of these insecticides pose serious risks of undesirable environmental impacts.

Environmental fate and exposure; neonicotinoids and fipronil.

Systemic insecticides are applied to plants using a wide variety of methods, ranging from foliar sprays to seed treatments and soil drenches. Neonicotinoids and fipronil are among the most widely used pesticides in the world. Their popularity is largely due to their high toxicity to invertebrates, the ease and flexibility with which they can be applied, their long persistence, and their systemic nature, which ensures that they spread to all parts of the target crop. However, these properties also increase the probability of environmental contamination and exposure of nontarget organisms. Environmental contamination occurs via a number of routes including dust generated during drilling of dressed seeds, contamination and accumulation in arable soils and soil water, runoff into waterways, and uptake of pesticides by nontarget plants via their roots or dust deposition on leaves. Persistence in soils, waterways, and nontarget plants is variable but can be prolonged; for example, the half-lives of neonicotinoids in soils can exceed 1,000 days, so they can accumulate when used repeatedly. Similarly, they can persist in woody plants for periods exceeding 1 year. Breakdown results in toxic metabolites, though concentrations of these in the environment are rarely measured. Overall, there is strong evidence that soils, waterways, and plants in agricultural environments and neighboring areas are contaminated with variable levels of neonicotinoids or fipronil mixtures and their metabolites (soil, parts per billion (ppb)-parts per million (ppm) range; water, parts per trillion (ppt)-ppb range; and plants, ppb-ppm range). This provides multiple routes for chronic (and acute in some cases) exposure of nontarget animals. For example, pollinators are exposed through direct contact with dust during drilling; consumption of pollen, nectar, or guttation drops from seed-treated crops, water, and consumption of contaminated pollen and nectar from wild flowers and trees growing near-treated crops. Studies of food stores in honeybee colonies from across the globe demonstrate that colonies are routinely and chronically exposed to neonicotinoids, fipronil, and their metabolites (generally in the 1-100 ppb range), mixed with other pesticides some of which are known to act synergistically with neonicotinoids. Other nontarget organisms, particularly those inhabiting soils, aquatic habitats, or herbivorous insects feeding on noncrop plants in farmland, will also inevitably receive exposure, although data are generally lacking for these groups. We summarize the current state of knowledge regarding the environmental fate of these compounds by outlining what is known about the chemical properties of these compounds, and placing these properties in the context of modern agricultural practices.

Translocation of neonicotinoid insecticides from coated seeds to seedling guttation drops: a novel way of intoxication for bees.

The death of honey bees, Apis mellifera L., and the consequent colony collapse disorder causes major losses in agriculture and plant pollination worldwide. The phenomenon showed increasing rates in the past years, although its causes are still awaiting a clear answer. Although neonicotinoid systemic insecticides used for seed coating of agricultural crops were suspected as possible reason, studies so far have not shown the existence of unquestionable sources capable of delivering directly intoxicating doses in the fields. Guttation is a natural plant phenomenon causing the excretion of xylem fluid at leaf margins. Here, we show that leaf guttation drops of all the corn plants germinated from neonicotinoid-coated seeds contained amounts of insecticide constantly higher than 10 mg/l, with maxima up to 100 mg/l for thiamethoxam and clothianidin, and up to 200 mg/l for imidacloprid. The concentration of neonicotinoids in guttation drops can be near those of active ingredients commonly applied in field sprays for pest control, or even higher. When bees consume guttation drops, collected from plants grown from neonicotinoid-coated seeds, they encounter death within few minutes.

Aluminum promotes neuronal plasticity events in a mouse neuroblastoma cell line.

The effects of aluminum(III) on microtubular meshwork have been investigated using cultured murine neuroblastoma cells grown in a medium containing aluminum lactate at defined metal concentrations (10-20 microM). A role of aluminum(III) in promoting neuronal plasticity events is suggested. These events including sprouting and neurite outgrowth are associated with an increased tyrosine-tubulin (Tyr-Tub) expression, which can be due to the enhanced needs of recently formed, highly dynamic microtubules typical of neuronal plasticity. After 48 and 72 h aluminum exposure, an upregulation of Tyr-Tub expression is detected and this is concentration-dependent. A high amount of Tyr-Tub is observed also in non-treated cells, although later than in aluminum-exposed cells. Thus, it is possible that aluminum(III) accelerates neuronal plasticity events, for which Tyr-Tub is confirmed to be a useful marker.

Headspace gas chromatographic determination of 2-alkyl-5,5-dimethyl-1,3-dioxane derivatives in wastewaters of a polyester resin plant.

The static headspace gas chromatographic technique can be conveniently employed to check the presence and amount of the odorous side-products, 2-R-1,3-dioxanes (R = H, CH3, C2H5, i-C3H7, n-C3H7), directly from the wastewaters flowing from the reactors during the synthesis of polyester resins. By the optimisation of a simple and direct analytical method, the amounts of these compounds may be continuously monitored and controlled. This method is characterized by good repeatability (3-4%) and does not seem to suffer from matrix effects. The detection limits for the determination of the five dioxanes fall in the range 400-700 micrograms dm-3 (alpha = beta = 0.05).

New possible chelating agents of clinical interest for iron(III): 2-hydroxynicotinic acid and 3-hydroxypicolinic acid. A thermodynamic study.

The formation of complexes between iron(III) and two ligands of possible relevance to chelation therapy, 2-hydroxynicotinic acid and 3-hydroxypicolinic acid, in aqueous 0.6 m (Na)Cl at 25 degrees C, has been investigated by means of potentiometric titrations and UV measurements. In both cases several mononuclear complexes and their deprotonation products are formed.

Direct determination of t,t-muconic acid in human urine by two-dimensional liquid chromatography.

The accurate determination of E,E-2,4-hexadiendioic acid (t,t-muconic acid), an important urinary biomarker of benzene exposure, is directly performed in human urine by a new two-dimensional liquid chromatographic method. After a first partial separation of urine components by a reversed-phase mechanism and the focalisation of the anionic analytes on a small anion-chromatographic column, a conventional ion-chromatographic analysis with UV detection is carried out. The analytical procedure is fully controlled by the HPLC instrumentation software using an eight-port switch valve. If compared with conventional one-dimensional procedures, the new method produces chromatograms containing a limited number of well resolved peaks and consequently allows better analytical performances: no interfering peaks, absence of bias, repeatability better than 5% in the concentration range 0.09-5 mg dm-3 and a detection limit of 4.0 micrograms dm-3 (alpha = beta = 0.05) for the analysis of real samples.

The multigene immunophilin family of Dictyostelium discoideum. Characterization of microsomal and mitochondrial cyclophilin isoforms.

The sequences of two cyclophilin (Cyp) isoforms from Dictyostelium discoideum have been determined. cyp2 is expressed as a 197 amino acid protein, which contains a 22 amino acid-long signal sequence, characteristic of endoplasmic reticulum localization signals, and that is cleaved in the mature protein. Mature Cyp2 has a molecular mass of 18 986 Da. The cyp3 gene encodes a 174 amino acid protein with a predicted molecular mass of 19 016 Da. Its sequence reveals no targeting sequence. From the MS analysis of affinity-purified cyclophilins from different subcellular compartments, we localized the previously described Cyp1 (Barisic K. et al., Dev. Genet. 12 (1991) 50-53) in cytosol, Cyp2 in microsomes and Cyp3 in mitochondria, respectively. The expression of cyp1 mRNA is constant during differentiation, whereas the mRNA level of both cyp2 and cyp3 is regulated and decreases steadily during development.

Cloning, sequencing and developmental expression of the genes encoding S4 and S10 ribosomal proteins in the cellular slime mould Dictyostelium discoideum.

The sequences of the rps4 and rps10 genes encoding the Dictyostelium discoideum homologues of the basic ribosomal proteins S4 and S10 were determined from cDNA and genomic DNA clones. They are expressed respectively as 266 and 153 amino-acid-long proteins. In both cases, the N-terminal methionine is cleaved in the mature proteins. S4 contains two putative nuclear targeting signals and displays a strong overall identity (around 60%) to eukaryotic S4 homologues. The rps10 gene harbours a 314-bp intron located close to its 5'-coding end. The overall identity between D. discoideum S10 and eukaryotic homologues is around 38% and rises to 53% in the N-terminal domain. Southern blots suggest that both S4 and S10 are encoded by single genes that are regulated during development. The corresponding mRNAs decrease sharply after 8 h of differentiation.

Weight Loss and Complications After Vertical Banded Gastroplasty.

We have performed 124 vertical banded gastroplasties (VBG) according to Mason, except that we used a collar 5.5 cm in circumference. We carried out a midline incision In 68 cases and a left subcostal incision in 56, with double application of a 2-row stapler with reinforcement In the first 69 cases and a single application of a 4-row stapler in 55 (15 with reinforcement, 40 without). We have followed 107 (86.2%) patients for a mean of 30 months (range 3-84). The mortality rate was nil. The intraoperative complications were three spleen lacerations (splenectomy), and the early complications were two gastric leaks (re-intervention) and one gastric bleeding. The late complications were one gastric perforation (re-intervention), four outlet stenoses (one re-intervention), one bleeding by collar erosion and nine ventral hernias (occurring only with the midline incision). The percentage excess weight loss was 46.3 +/- 16.4 at 6 months, 53.4 +/- 17.9 at 1 year, 47.8 +/- 19.6 at 3 years, and 45 +/- 23.3 at 5 years. In 12 cases the weight loss was unsatisfactory (less than 30% of the initial excess weight). Often such failures were due to staple-line disruption. We have had no staple-line disruptions since we stopped performing the reinforcement. VBG has a low incidence of complications, but sometimes these may be serious. In our opinion, the technical procedures which offer a stronger vertical partition give better results for weight loss.

A long-term toxicological investigation on the effect of tris(maltolate)aluminum(III) in rabbits.

The toxicity of i.v. injected hydrophilic aluminum complex tris(maltolate)aluminum(III) was studied in New Zealand white rabbits for a period of time ranging from 5 to 63 wk. Animals were injected 3-5 times a week with 1 mL of 7.5 mM Al(malt)3 and one rabbit with a dose 10 times higher after 14 wk of treatment. Autopical examination was performed on all animals. Chemoclinical analysis (glucose, urea, creatinine, cholesterol, bilirubin, alanin aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl-transferase, LDH, CK, total protein, triglycerides, and Ca2+) gave no variation in treated animals with respect to the control. The toxicological data show a moderate systemic general toxicity at doses far higher than those used in similar previous experiments using Al(acac)3 (acac = 2,4 pentanedionate), a hydrolytically stable and more lipophilic aluminum(III) complex (1). The diversity of behavior is discussed in terms of metal speciation as well as respect to the thermodynamic and kinetic properties of the two complexes in aqueous solution. The toxicological model presented here emphasizes that neutral, water compatible aluminum(III) complexes are to be considered as promising tools for toxicological experiments providing biological models of human pathologies.

Experimental aluminum pathology in rabbits: effects of hydrophilic and lipophilic compounds.

Aluminum lactate [Al(lact)3] (hydrophilic, hydrolytically unstable) and aluminum acetylacetonate [Al(acae)3] (lipophilic, hydrolytically stable) were tested as potential toxicants to rabbits upon IV administration both as aqueous solutions and as liposome suspensions. Both chemicals behaved as cardiotoxic agents when administered as aqueous solutions, but Al(acae)3 was at least two orders of magnitude more active than Al(lact)3. Al(acae)3, but not Al(lact)3, caused myocardial infarcts resembling those in humans (with contraction bands) at doses as low as 0.24 mg/kg body weight, as well as a prominent acanthocytosis. Al(lact)3, when administered as a liposome suspension, was about 300 times more toxic than in aqueous solution, although cardiac damage was not infarctual in character. Both chemical and physical speciation of aluminum(III) thus play an essential role in determining the toxicity of the metal.

[Ano-rectal candidiasis]. / La candidosi ano-rettale.

The presence of candida and other fungi was investigated in 300 patients referred with anal problems of diverse aetiology. Candida was present in 13% and played a pathogenic role in about 50% of all positive cultures. It is concluded that cultural tests for fungal pathogens should always be performed in cases of anal itching or burning combined with other anal skin problems.