The prolyl-aminodipeptidases and their inhibitors as therapeutic targets for fibrogenic disorders

Many biologically active peptides are protected from general proteolytic degradation by evolutionary conserved prolines (Pro), due to conformational constraints imposed by the Pro residue. Thus the biological importance of prolyl-specific peptidases points to a high potential for drug discovery for this family of enzymes. Panels of inhibitors have been synthesized and their effects, determined in biological models, suggest the inhibition of families of enzymes with similar activities. Prolyl-specific aminodipeptidases include dipeptidyl-aminodipeptidase IV (DPP IV)/CD26, DPP8, DPP9 and fibroblast activation protease-alpha (FAP-alpha)/seprase, able to release X-Pro dipeptides from the N-terminus of peptides. DPP IV inhibitors are in clinical use for type 2 diabetes. In this review, the expression and the potential functions of prolyl-aminodipeptidases are reviewed in diseases, and the inhibitors developed for these enzymes are discussed, with a specific focus on inhibitors able to discriminate between DPP IV and fibroblast activation protease-alpha (FAPalpha)/seprase as potential leads for the treatment of fibrogenic diseases.

Cannabis Use in Patients with Fibromyalgia: Effect on Symptoms Relief and Health-Related Quality of Life

Background: The aim of this study was to describe the patterns of cannabis use and the associated benefits reported by patients with fibromyalgia (FM) who were consumers of this drug. In addition, the quality of life of FM patients who consumed cannabis was compared with FM subjects who were not cannabis users. Methods: Information on medicinal cannabis use was recorded on a specific questionnaire as well as perceived benefits of cannabis on a range of symptoms using standard 100-mm visual analogue scales (VAS). Cannabis users and non-users completed the Fibromyalgia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index (PSQI) and the Short Form 36 Health Survey (SF-36). Results: Twenty-eight FM patients who were cannabis users and 28 non-users were included in the study. Demographics and clinical variables were similar in both groups. Cannabis users referred different duration of drug consumption; the route of administration was smoking (54%), oral (46%) and combined (43%). The amount and frequency of cannabis use were also different among patients. After 2 hours of cannabis use, VAS scores showed a statistically significant (p<0.001) reduction of pain and stiffness, enhancement of relaxation, and an increase in somnolence and feeling of well being. The mental health component summary score of the SF-36 was significantly higher (p<0.05) in cannabis users than in non-users. No significant differences were found in the other SF-36 domains, in the FIQ and the PSQI. Conclusions: The use of cannabis was associated with beneficial effects on some FM symptoms. Further studies on the usefulness of cannabinoids in FM patients as well as cannabinoid system involvement in the pathophysiology of this condition are warranted

Design, synthesis, and biological and crystallographic evaluation of novel inhibitors of Plasmodium falciparum enoyl-ACP-reductase (PfFabI).

Malaria, a disease of worldwide significance, is responsible for over one million deaths annually. The liver-stage of Plasmodium's life cycle is the first, obligatory, but clinically silent step in malaria infection. The P. falciparum type II fatty acid biosynthesis pathway (PfFAS-II) has been found to be essential for complete liver-stage development and has been regarded as a potential antimalarial target for the development of drugs for malaria prophylaxis and liver-stage eradication. In this paper, new coumarin-based triclosan analogues are reported and their biological profile is explored in terms of inhibitory potency against enzymes of the PfFAS-II pathway. Among the tested compounds, 7 and 8 showed the highest inhibitory potency against Pf enoyl-ACP-reductase (PfFabI), followed by 15 and 3. Finally, we determined the crystal structures of compounds 7 and 11 in complex with PfFabI to identify their mode of binding and to confirm outcomes of docking simulations.

Water stress before harvest of pepper-rosmarin

The objective of this work was to assess the effect of different periods of water stress before harvest of pepper-rosmarin (Lippia sidoides) on the contents of essential oil and flavonoids. The experiment was carried out during 270 days of cultivation, with drainage lysimeters, in a completely randomized block design with five treatments: 0, 2, 4, 6, and 8 days of water suppression before harvest, with four replicates. Fresh and dry matter yield, essential oil content, total flavonoids content, and water potential and temperature of leaves were determined. There was a decrease of approximately 50% in oil content and of 60% in total flavonoid content with the reduction of leaf water potential in 0.3 MPa. Essential oil is more sensitive to water stress than total flavonoids.

Beneficial bacterial strains on Agaricus blazei cultivation

The objective of this work was to evaluate the effects of six bacterial strains isolated from Agaricus blazei (ABM) on its cultivation. The six strains were characterized as to their effects on the productivity, polysaccharide-protein complex (PSPC), and polysaccharide contents of ABM cultured on sterilized casing soils. Three isolates enhanced ABM mycelium growth. Inoculation of Arthrobacter sp. or Exiguobacterium sp. on sterile peat casing soil resulted in 64% increase in ABM mushroom total fresh matter yield compared to the uninoculated control. Inoculation of Exiguobacterium sp., Microbacterium esteraromaticum or Pseudomonas resinovorans on sterilized loamy casing soil resulted in 62, 95, and 59% increase in ABM mushroom total fresh matter yield, respectively. The PSPC content in ABM increased 7 to 10% in casing soil inoculated with five of the six isolates compared to the uninoculated control. Exiguobacterium sp. inoculated on casing soil resulted in a mushroom-polysaccharide content 15% higher than the control. Moreover, inoculation of five of the six isolates on the casing soil reduced the harvesting time from 10 to 27 days. The evaluated beneficial microbes improve the yield, PSPC, and polysaccharide contents, besides reducing the harvesting time in ABM culture.

Exploring the space of histidine containing dipeptides in search of novel efficient RCS sequestering agents.

The study reports a set of forty proteinogenic histidine-containing dipeptides as potential carbonyl quenchers. The peptides were chosen to cover as exhaustively as possible the accessible chemical space, and their quenching activities toward 4-hydroxy-2-nonenal (HNE) and pyridoxal were evaluated by HPLC analyses. The peptides were capped at the C-terminus as methyl esters or amides to favor their resistance to proteolysis and diastereoisomeric pairs were considered to reveal the influence of configuration on quenching. On average, the examined dipeptides are less active than the parent compound carnosine (βAla + His) thus emphasizing the unfavorable effect of the shortening of the βAla residue as confirmed by the control dipeptide Gly-His. Nevertheless, some peptides show promising activities toward HNE combined with a remarkable selectivity. The results emphasize the beneficial role of aromatic and positively charged residues, while negatively charged and H-bonding side chains show a detrimental effect on quenching. As a trend, ester derivatives are slightly more active than amides while heterochiral peptides are more active than their homochiral diastereoisomer. Overall, the results reveal that quenching activity strongly depends on conformational effects and vicinal residues (as evidenced by the reported QSAR analysis), offering insightful clues for the design of improved carbonyl quenchers and to rationalize the specific reactivity of histidine residues within proteins.

Constrained peptidomimetics reveal detailed geometric requirements of covalent prolyl oligopeptidase inhibitors.

Prolyl oligopeptidases cleave peptides on the carboxy side of internal proline residues and their inhibition has potential in the treatment of human brain disorders. Using our docking program fitted, we have designed a series of constrained covalent inhibitors, built from a series of bicyclic scaffolds, to study the optimal shape required for these small molecules. These structures bear nitrile functional groups that we predicted to covalently bind to the catalytic serine of the enzyme. Synthesis and biological assays using human brain-derived astrocytic cells and endothelial cells and human fibroblasts revealed that these compounds act as selective inhibitors of prolyl oligopeptidase activity compared to prolyl-dipeptidyl-aminopeptidase activity, are able to penetrate the cells and inhibit intracellular activities in intact living cells. This integrated computational and experimental study shed light on the binding mode of inhibitors in the enzyme active site and will guide the design of future drug-like molecules.

Cultivation of Flammulina velutipesmushroom using various agro-residues as a fruiting substrate

The objective of this work was to evaluate the feasibility of different agro-residues as a carbon source in the fruiting substrates of Flammulina velutipesmushroom and the effect of supplementation with the nitrogen sources spent brewer's yeast and rice bran. The following fruiting substrates were evaluated: rubber wood sawdust (SD), paddy straw (PS), palm empty fruit bunches (EFB), and palm-pressed fiber (PPF). Cultivation was done on each agro-residue, based on formulations consisting of two substrates at the ratios of 3:1, 1:1, and 1:3. Mycelial growth rate and basidiocarp yield were evaluated. The best fruiting substrates were PS+EFB (25:75), PS+PPF (50:50), and PPF (100), with biological efficiency of 185.09±36.98, 150.89±50.35, and 129.06±14.51%, respectively. No significant effects of supplementation with rice bran and spent yeast were observed on mycelial growth rate and biological efficiency. The cultivation of F. velutipes on oil palm wastes does not require additional nitrogen sources.

Qualitative structure-metabolism relationships in the hydrolysis of carbamates.

The aims of this review were 1) to compile a large number of reliable literature data on the metabolic hydrolysis of medicinal carbamates and 2) to extract from such data a qualitative relation between molecular structure and lability to metabolic hydrolysis. The compounds were classified according to the nature of their substituents (R³OCONR&supl;R²), and a metabolic lability score was calculated for each class. A trend emerged, such that the metabolic lability of carbamates decreased (i.e., their metabolic stability increased), in the following series: Aryl-OCO-NHAlkyl >> Alkyl-OCO-NHAlkyl ~ Alkyl-OCO-N(Alkyl)? ? Alkyl-OCO-N(endocyclic) ? Aryl-OCO-N(Alkyl)? ~ Aryl-OCO-N(endocyclic) ? Alkyl-OCO-NHAryl ~ Alkyl-OCO-NHAcyl?>> Alkyl-OCO-NH? > Cyclic carbamates. This trend should prove useful in the design of carbamates as drugs or prodrugs.

Novel 2-[(benzylamino)methyl]pyrrolidine-3,4-diol derivatives as alpha-mannosidase inhibitors and with antitumor activities against hematological and solid malignancies.

Novel alpha-mannosidase inhibitors of the type (2R,3R,4S)-2-({[(1R)-2-hydroxy-1-arylethyl]amino}methyl)pyrrolidine-3,4-diol have been prepared and assayed for their anticancer activities. Compound 30 with the aryl group=4-trifluoromethylbiphenyl inhibits the proliferation of primary cells and cell lines of different origins, irrespective of Bcl-2 expression levels, inducing a G2/Mcell cycle arrest and by modification of genes involved in cell cycle progression and survival.

Natural aphrodisiacs: studies of commercially-available herbal recipes, and phytochemical investigation of "Erythroxylum vacciniifolium" Mart. (Erythroxylaceae) from Brazil

De tout temps, hommes et femmes ont cherché par tous les moyens à développer, préserver ou recouvrer leurs propres capacités sexuelles mais également à stimuler le désir du partenaire. L?utilisation d?aphrodisiaques naturels a été l?un des recours les plus répandus. De nos jours, la commercialisation de nouvelles "love drugs" de synthèse, e.g. Viagra®, Cialis®, Levitra®, a remis au goût du jour les aphrodisiaques classiques et à relancer la recherche sur des molécules nouvelles. La pratique croissante de l?automédication, le matraquage publicitaire sur les aphrodisiaques naturels, la prolifération sur le marché de compléments alimentaires non contrôlés et l?absence de véritable législation accroissent les risques qui pèsent sur la santé publique. Dans le but d?évaluer les risques potentiels sur le consommateur de produits aphrodisiaques commercialisés, le développement et la validation d?une méthode rapide d?analyse qualitative et quantitative de la yohimbine dans ces préparations du marché sont exposés dans la première partie de ce travail. La yohimbine est un antagoniste ?2-adrénocepteur du système nerveux central et périphérique, elle est employée depuis plus d?un siècle dans le traitement des dysfonctionnements érectiles. Cette méthode analytique utilise la chromatographie liquide couplée à l?ultraviolet et à la spectrométrie de masse (LC-UV-MS) et au total, vingt préparations aphrodisiaques ont été étudiées. La dose journalière de yohimbine mesurée s?est révélée très variable selon les produits puisqu?elle varie de 1.32 à 23.16 mg. La seconde partie de ce travail concerne l?étude phytochimique et pharmacologique d?Erythroxylum vacciniifolium Mart. (Erythroxylaceae), une plante, appelée localement catuaba, utilisée dans la médecine traditionnelle brésilienne comme tonique et aphrodisiaque. Dans un premier temps, l?extrait alcaloïdique a été analysé par chromatographie liquide haute performance (HPLC) couplée soit à un détecteur UV à barrette d?iode (LC-UV-DAD), soit à un spectromètre de masse (LC-MS), ou soit à un spectromètre de résonance magnétique nucléaire (LC-RMN). L?interprétation de ces données spectrales enregistrées en ligne a permis d?obtenir des informations structurales et d?identifier partiellement près de 24 alcaloïdes appartenant à la classe des tropanes et potentiellement originaux. Par des méthodes classiques de chromatographie liquide sur l?extrait alcaloïdique de la plante, dix sept tropanes nouveaux ont ensuite été isolés dont les catuabines et leurs dérivés, et les vaccinines. Tous ces composés sont des tropane-diols ou triols estérifiés par au moins un groupe acide 1-méthyl-1H-pyrrole-2-carboxylique. Un de ces composés a été identifié comme un tropane N-oxyde. Toutes les structures ont été déterminées par spectrométrie de masse haute résolution et spectroscopie RMN multi-dimensionnelle. Parmi les nombreux tests biologiques réalisés sur ces tropanes, seuls les tests de cytotoxicité se sont révélés faiblement positifs pour certains de ces composés.<br/><br/>Throughout the ages, men and women have incessantly pursued every means to increase, preserve or recapture their sexual capacity, or to stimulate the sexual desire of selected individuals. One of the most recurrent methods has been the use of natural aphrodisiacs. Nowadays, the commercialization of new synthetic "love drugs", e.g. Viagra®, Cialis® and Levitra®, has fascinated the public interest and has led to a reassessment of classical aphrodisiacs and to the search for new ones. The practice of self-medication by an increasing number of patients, the incessant aggressive advertising of these herbal aphrodisiacs, the invasion of the medicinal market with uncontrolled dietary supplements and the absence of real directives amplifies the potential health hazards to the community. In order to evaluate the possible risks of commercialized aphrodisiac products on consumer health, the development and validation of a rapid qualitative and quantitative method for the analysis of yohimbine in these products, is reported in the first part of the present work. Yohimbine, a pharmacologically well-characterized ?2-adrenoceptor antagonist with activity in the central and peripheral nervous system, has been used for over a century in the treatment of erectile dysfunction. The analytical method is based on liquid chromatography coupled with ultraviolet and mass spectrometry (LC-UV-MS) and in total, 20 commercially-available aphrodisiac preparations were analyzed. The amount of yohimbine measured and expressed as the maximal dose per day suggested on product labels ranged from 1.32 to 23.16 mg. The second part of this work involved the phytochemical and pharmacological investigation of Erythroxylum vacciniifolium Mart. (Erythroxylaceae), a plant used in Brazilian traditional medicine as an aphrodisiac and tonic, and locally known as catuaba. With the aim of obtaining preliminary structure information on-line, the alkaloid extract was analyzed by high performance liquid chromatography (HPLC) coupled to diode array UV detection (LC-UVDAD), to mass spectrometry (LC-MS) and to nuclear magnetic resonance spectroscopy (LCNMR). Interpretation of on-line spectroscopic data led to structure elucidation and partial identification of 24 potentially original alkaloids bearing the same tropane skeleton. Seventeen new tropane alkaloids were then isolated from the alkaloid extract of the plant, including catuabines D to I, their derivatives and vaccinines A and B. All compounds were elucidated as tropane-diol or -triol alkaloids esterified by at least one 1-methyl-1H-pyrrole-2-carboxylic acid. One of the isolated compounds was identified as a tropane alkaloid N-oxide. Their structures were determined by high resolution mass spectrometry and multi-dimensional NMR spectroscopy. Among the numerous bioassays undertaken, only the cytotoxicity tests exhibited a weak positive activity of certain compounds.

Phytochemical investigation of plants used in African traditional medicine: "Dioscorea sylvatica" (Dioscoreaceae), "Urginea altissima" (Liliaceae), "Jamesbrittenia fodina" and "Jamesbrittenia elegantissima" (Scrophulariaceae)

Les plantes médicinales représentent la seule source de médicaments pour près de 90 % de la population de certains pays d?Afrique. Le savoir-faire des guérisseurs traditionnels, d?une valeur inestimable, représente un point de départ pour l?investigation pharmacologique et phytochimique de ces médicaments naturels. Dans le cadre de ce travail, nous nous sommes dans un premier temps intéressés à valider l?utilisation en médecine traditionnelle de deux plantes, Diuscorea sylvatica (Dioscoreaceae) et Urginea altissima (Liliaceae), qui produisent, lorsqu?elles sont frottées sur la peau, une inflammation et des démangeaisons. Ces réactions cutanées ont pu être expliquées, au moins en partie, par la présence d?aiguilles acérées d?oxalate de calcium dans les organes souterrains. Ces microtraumatismes répétés de l?épiderme risquent de provoquer, lors d?une utilisation prolongée, des lésions granulomateuses. L?histamine n?a pas été détectée, mais d?autres substances pourraient être impliquées dans le processus inflammatoire. La seconde partie de ce travail a consisté en la détection, l?isolement et la caractérisation de nouveaux composés naturels présentant un intérêt thérapeutique potentiel. 70 extraits provenant de 28 plantes supérieures du Zimbabwe ont été soumis à un criblage chimique et biologique. Les extraits méthanoliques des parties aériennes de Jamesbrittenia fodina et J. elegantissima (Scrophulariaceae) ont été sélectionnés sur la base de leurs nombreuses activités. Le fractionnement guidé par l?activité de J. fudina a permis l?isolement des saponines A et B, responsables des activités antifongique, antibactérienne et molluscicide de l?extrait. De plus, les deux saponines ont montré une activité équivalente en tant qu?inhibiteurs de l?acétylcholinestérase, propriété encore non décrite pour cette classe de composés. Une analyse LC/uv/MS de l?extrait a permis d?attribuer l?activité antiradicalaire au verbascoside, un dérivé du phenylpropane; cette analyse a de plus montré la présence d?une série de dérivés de l?acide cinnamique, dont l?isolement a été entrepris. Deux problèmes d?instabilité sont apparus, empêchant l?isolement des composés par des méthodes chromatographiques de pointe, en dépit de très bonnes conditions de séparations. Des analyses LC/?H-NMR combinées à des analyses RMN classiques des mélanges ont permis d?attribuer ces instabilités d?une part à une isomérisation cis/trans induite par la lumière, et d?autre part à une transacylation du groupe cinnamoyl sur une unité de sucre. Ceci a permis l?identification de 12 esters cinnamiques d?iridoïdes, dont 8 nouveaux produits naturels. Ces dérivés présentent un intérêt thérapeutique, car des composés similaires ont montré des propriétés anti-inflammatoires significatives dans différents modèles in vivo. Deux flavanones ont aussi été isolées de l?extrait. Cette classe de composés n?a jamais été rapportée chez un membre des Scrophulariaceae. Une analyse LC/UV/MS comparative des extraits polaires des deux espèces, J. fodina et J. elegantissima, a été effectuée pour détecter la présence éventuelle de compos.és communs. Les saponines A et B et le verbascoside ont été identifiés dans l?extrait de J. elegantissima. Trois flavonoïdes ont de plus été isolés de ce dernier par CPC et HPLC semi-préparative.<br/><br/>In certain African countries, medicinal plants represent the unique source of to 90% of the population. The knowledge of traditional healers represents a basis for the pharmacological and phytochemical investigation of these natural medicines. This work first focused on the validation of use of two plants frequently employed in traditional medicine, Dioscorea sylvatica (Dioscoreaceae) and Urginea altissimu (Liliaceae), which produce mild inflammation and itching when rubbed on the skin. These cutaneous reactions were shown to be due, at least in part, to the presence of sharp needles of calcium oxalate, implying the risk of granulomatous lesions following a long term use. Histamine was not detected, but other compounds could be involved in the inflammatory process. The second part of this work consisted of the detection, isolation and characterisation of new natural compounds of potential therapeutic interest from African plants. Seventy extracts obtained from 28 higher plants of Zimbabwe were submitted to a chemical and biological screening. The methanol extracts of the whole plants of Jamesbrittenia fodina and J. elegantissima (Scrophulariaceae) were selected for their various activities. An activity-guided fractionation of J. fodina led to the isolation of the saponins A and B, responsible for the antifungal, antibacterial and molluscicidal properties. Both saponins were equally active as inhibitors of acetylcholinesterase, a property that has, to our knowledge, never been described for this class of compounds. A LC/UV/MS analysis of the extract allowed the identification of verbascoside as the product with radical scavenging activity, and indicated the presence of a series of potentially interesting cinnamic acid derivatives. Two types of instability problems occurred in the course of their isolation, as some compounds could not be separated despite very good chromatographic conditions. LC/'H-NMR analyses combined with in-mixture NMR analyses enabled the attribution of the cause of the instability in one case to a cidtrans light-induced isomerisation, and in the other case to a transacylation of the cinnamoyl moiety on a sugar residue. These problems of instability have not been the object of previous studies. 12 cinnamic iridoid esters could be characterised, 8 of these being new natural compounds. Several similar substances have displayed significant anti-inflammatory properties in different in vivo models, suggesting a therapeutic interest for these new derivatives. Two flavanones were isolated from the same extract. This class of compound has not been previously reported from species of the Scrophulariaceae family. A comparative LCAJVNS study of the polar extracts of the two species J. elegantissima and J. fodina was performed in order to detect possible common compounds. Saponins A and B and verbascoside were thus identified in .J. elegantissima. Moreover, three supplementary flavonoids were isolated from J. elegantissima..

Empirical models for predicting the production of wild mushrooms in Scots pine (Pinus sylvestris L.) forests in the Central Pyrenees

Mushroom picking has become a widespread autumn recreational activity in the Central Pyrenees and other regions of Spain. Predictive models that relate mushroom production or fungal species richness with forest stand and site characteristics are not available. This study used mushroom production data from 24 Scots pine plots over 3 years to develop a predictive model that could facilitate forest management decisions when comparing silvicultural options in terms of mushroom production. Mixed modelling was used to model the dependence of mushroom production on stand and site factors. The results showed that productions were greatest when stand basal area was approximately 20 m2 ha-1. Increasing elevation and northern aspect increased total mushroom production as well as the production of edible and marketed mushrooms. Increasing slope decreased productions. Marketed Lactarius spp., the most important group collected in the region, showed similar relationships. The annual variation in mushroom production correlated with autumn rainfall. Mushroom species richness was highest when the total production was highest.

A single epidermal stem cell strategy for safe ex vivo gene therapy.

There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells before they are transplanted. To address this, we have developed a strategy that permits transplantation of a clonal population of genetically corrected autologous stem cells that meet stringent selection criteria and the principle of precaution. As a proof of concept, we have stably transduced epidermal stem cells (holoclones) obtained from a patient suffering from recessive dystrophic epidermolysis bullosa. Holoclones were infected with self-inactivating retroviruses bearing a COL7A1 cDNA and cloned before the progeny of individual stem cells were characterised using a number of criteria. Clonal analysis revealed a great deal of heterogeneity among transduced stem cells in their capacity to produce functional type VII collagen (COLVII). Selected transduced stem cells transplanted onto immunodeficient mice regenerated a non-blistering epidermis for months and produced a functional COLVII. Safety was assessed by determining the sites of proviral integration, rearrangements and hit genes and by whole-genome sequencing. The progeny of the selected stem cells also had a diploid karyotype, was not tumorigenic and did not disseminate after long-term transplantation onto immunodeficient mice. In conclusion, a clonal strategy is a powerful and efficient means of by-passing the heterogeneity of a transduced stem cell population. It guarantees a safe and homogenous medicinal product, fulfilling the principle of precaution and the requirements of regulatory affairs. Furthermore, a clonal strategy makes it possible to envision exciting gene-editing technologies like zinc finger nucleases, TALENs and homologous recombination for next-generation gene therapy.

Zoonotic occupational diseases in forestry workers: Lyme borreliosis, tularemia and leptospirosis in Europe

INTRODUCTION: Forestry workers and other people who come into close contact with wild animals, such as hunters, natural science researchers, game managers or mushroom/berry pickers, are at risk of contracting bacterial, parasitological or viral zoonotic diseases. Synthetic data on the incidence and prevalence of zoonotic diseases in both animals and humans in European forests do not exist. It is therefore difficult to promote appropriate preventive measures among workers or people who come into direct or indirect contact with forest animals. OBJECTIVES: The objectives of this review are to synthesise existing knowledge on the prevalence of the three predominant bacterial zoonotic diseases in Europe, i.e. Lyme borreliosis, tularemia and leptospirosis, in order to draw up recommendations for occupational or public health. METHODS: 88 papers published between 1995-2013 (33 on Lyme borreliosis, 30 on tularemia and 25 on leptospirosis) were analyzed. CONCLUSIONS: The prevalences of these three zoonotic diseases are not negligible and information targeting the public is needed. Moreover, the results highlight the lack of standardised surveys among different European countries. It was also noted that epidemiological data on leptospirosis are very scarce.