Genetic determinants of micronucleus formation in vivo.

Genomic instability arising from defective responses to DNA damage1 or mitotic chromosomal imbalances2 can lead to the sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of ageing and diseases associated with genomic instability, the catalogue of genetic players that regulate the generation of MN remains to be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases (n = 71) or decreases (n = 74) MN formation, including many genes whose orthologues are linked to human disease. We found that mice null for Dscc1, which showed the most significant increase in MN, also displayed a range of phenotypes characteristic of patients with cohesinopathy disorders. After validating the DSCC1-associated MN instability phenotype in human cells, we used genome-wide CRISPR-Cas9 screening to define synthetic lethal and synthetic rescue interactors. We found that the loss of SIRT1 can rescue phenotypes associated with DSCC1 loss in a manner paralleling restoration of protein acetylation of SMC3. Our study reveals factors involved in maintaining genomic stability and shows how this information can be used to identify mechanisms that are relevant to human disease biology1.

Collaborative study for the validation of cell line assays for in-process toxicity and antigenicity testing of Clostridium septicum vaccine antigens - Part 2: Optimisation of cell line assays.

During the production of clostridial vaccines large numbers of mice are used for various in-process control tests. Replacement in vitro assays had been developed for the testing of the toxins and toxoids of several clostridial species, but none of these assays had been assessed in an international collaborative study. Under the common aegis of the European Partnership for Alternative Approaches to Animal Testing (EPAA) and of the European Directorate for the Quality of Medicines & HealthCare (EDQM), a project on clostridial vaccines for veterinary use was started as part of the EDQM-co-ordinated Biological Standardisation Programme (BSP). Within the framework of this project (coded BSP130) a collaborative study was organised to evaluate Vero cell-based alternative methods to the current mouse tests used to measure: i) the toxicity of Clostridium septicum toxin, ii) the absence of toxicity of C. septicum toxoid and iii) the antigenicity of C. septicum toxoid. The principal aims of the study were to determine the repeatability and reproducibility of the in vitro assays and to demonstrate concordance of the in vitro and current in vivo tests. The study results demonstrated good concordance, but the information gathered through the study (later on called Part 1) and the participants' workshop prompted the extension of the project in order to further optimise the in vitro protocols and improve their repeatability and reproducibility, which were comparable to but not better than those of the in vivo assays in Part 1. The 3 in vitro assays to be optimised in the extension of the BSP130 project were : i) the in vitro toxin neutralisation equivalence plus (TNE+), as a replacement for the in vivo minimum lethal dose (MLD) test for quantification of the toxicity of toxin; ii) the in vitro MLD, as a replacement for the in vivo MLD test for detection of residual toxicity associated with toxoid; iii) the in vitro total combining power (TCP), as a replacement for the in vivo TCP test for quantification of the antigenicity of toxoid. At this point, the Analytical Method Transfer Laboratory of Ceva-Phylaxia (Hungary), supported by the project management team, developed suitable SOPs for the 3 in vitro assays. These optimised methods were further assessed in BSP130 through a second international collaborative study (Part 2) aimed at defining repeatability and reproducibility in different laboratories and determining the levels of improvement compared with the original in vivo tests and the initial in vitro assays used in Part 1 of the project. Fourteen laboratories, comprising 4 public sector and 10 manufacturers' medicines control laboratories, from 11 countries participated in the collaborative Part 2 study, each testing 6 different C. septicum toxins and 6 C. septicum toxoids. Improved repeatability and reproducibility were observed for the optimised assays. The results of this study confirm the suitability of these assays for in-process control of C. septicum vaccines, with better repeatability and reproducibility than their in vivo equivalents. It is expected that, with appropriate minor changes and the use of relevant reagents, these optimised in vitro assays could be used not only for the assessment of C. septicum toxins and toxoids but for all cytotoxin-based clostridial antigens. The development and implementation of such in vitro assays would offer a great opportunity to significantly reduce animal usage, shorten the duration of QC test procedures and increase the precision of toxicity and antigenicity assays in clostridial veterinary vaccine in-process control. This would also provide more accurate and reproducible dosing of antigens in the final vaccine products, help to promote compendial acceptance and to proffer a basis for improved international harmonisation across this area of product testing.

Risk stratification of EGFR+ lung cancer diagnosed with panel-based next-generation sequencing.

OBJECTIVE: Panel-based next-generation sequencing (NGS) is increasingly used for the diagnosis of EGFR-mutated non-small-cell lung cancer (NSCLC) and could improve risk assessment in combination with clinical parameters. MATERIALS AND METHODS: To this end, we retrospectively analyzed the outcome of 400 tyrosine kinase inhibitor (TKI)-treated EGFR+ NSCLC patients with validation of results in an independent cohort (n = 130). RESULTS: EGFR alterations other than exon 19 deletions (non-del19), TP53 co-mutations, and brain metastases at baseline showed independent associations of similar strengths with progression-free (PFS hazard ratios [HR] 2.1-2.3) and overall survival (OS HR 1.7-2.2), in combination defining patient subgroups with distinct outcome (EGFR+NSCLC risk Score, "ENS", p < 0.001). Co-mutations beyond TP53 were rarely detected by our multigene panel (<5%) and not associated with clinical endpoints. Smoking did not affect outcome independently, but was associated with non-del19 EGFR mutations (p < 0.05) and comorbidities (p < 0.001). Laboratory parameters, like the blood lymphocyte-to-neutrophil ratio and serum LDH, correlated with the metastatic pattern (p < 0.01), but had no independent prognostic value. Reduced ECOG performance status (PS) was associated with comorbidities (p < 0.05) and shorter OS (p < 0.05), but preserved TKI efficacy. Non-adenocarcinoma histology was also associated with shorter OS (p < 0.05), but rare (2-3 %). The ECOG PS and non-adenocarcinoma histology could not be validated in our independent cohort, and did not increase the range of prognostication alongside the ENS. CONCLUSIONS: EGFR variant, TP53 status and brain metastases predict TKI efficacy and survival in EGFR+ NSCLC irrespective of other currently available parameters ("ENS"). Together, they constitute a practical and reproducible approach for risk stratification of newly diagnosed metastatic EGFR+ NSCLC.

Collaborative study for the validation of cell line assays for in-process toxicity and antigenicity testing of Clostridium septicum vaccine antigens - Part 1.

Large numbers of mice are used in testing during the production of Clostridial vaccines. Previous work has indicated that cell line assays could replace mouse tests for certain aspects of this testing. Replacement assays have been developed for the testing of the toxins and toxoids of several clostridial species but none of these assays have been assessed in an international collaborative study. Under the common aegis of the European Partnership for Alternative Approaches to Animal Testing (EPAA) and of the European Directorate for the Quality of Medicines & HealthCare (EDQM), collaborative study BSP130 was initiated to evaluate Vero cell based alternative methods to the current mouse tests used to measure the toxicity of Clostridium septicum toxin (the minimum lethal dose (MLD) test), the freedom from toxicity of C. septicum toxoid (the MLD test) and the antigenicity of C. septicum toxoid (the total combining power (TCP) test). The principal aims of BSP130 were to determine the repeatability and reproducibility of the in vitro assays and to demonstrate concordance of the proposed in vitro and current in vivo TCP and MLD tests. 11 laboratories from 7 countries participated in the collaborative study and each tested 6 toxins and 6 toxoids. The participants' Vero cell lines were up to 1 000 times more sensitive than the mouse strains. The MLD assay in mice and on Vero cells generally ranked the toxins in a similar order in most of the laboratories. The TCP assay in mice and on Vero cells also generally ranked the toxoids in a similar order in most of the laboratories. The results demonstrate that the repeatability and reproducibility of the in vitro Vero cell based assays are no worse than that of the in vivo assays and that they are easily transferable to other laboratories. The concordance correlations between the in vivo and in vitro methods were for the MLD assays ρc=0.961 (log-transformed values) and ρc=0.921 (non-log-transformed values) and for the TCP assays ρc=0.968 (log-transformed values) and ρc=0.980 (non log-transformed values). These correlations are excellent showing that the Vero cell assays can be used as alternatives to the mouse tests for the assessment of C. septicum toxin MLD and toxoid TCP values. This study can be used by vaccine manufacturing companies as a guide for applying the same approach to other clostridial toxins and toxoids.

[Residual limb and phantom pain : Causes and therapeutic approaches]. / Stumpf- und Phantomschmerzen : Ursachen und Therapieansätze.

INTRODUCTION: Residual limb pain and phantom pain are severe complications following an amputation. Various reasons are responsible for these complaints. It must be distinguished between amputation stump pain, phantom sensations and phantom pain. CAUSE AND THERAPY: In this paper we describe the most common reasons for stump pain and propose some non-operative therapeutic approaches. Furthermore path physiology and phantom pain therapy will be discussed. The recommendations offered in this paper are based on practical experience over three decades in a specialized out-patient department for patients with amputation injuries.

EDQM biological reference preparation for rabies vaccine (inactivated) for veterinary use.

Rabies is a deadly zoonotic disease. Control of rabies in animals by vaccination is an important strategy to protect humans from infection and control the spread of the disease. Requirements for the quality control of rabies vaccines (inactivated) for veterinary use include an in vivo quantitative potency determination as outlined in the Ph. Eur. monograph 0451. Performance of this assay requires a reference preparation calibrated in International Units (IU). A European Pharmacopeia (Ph. Eur.) Biological Reference Preparation (BRP) for rabies vaccines (inactivated) for veterinary use, calibrated in IU, has been established for this purpose. Due to the dwindling stocks of the current batch (batch 4) of Ph. Eur. BRP for rabies vaccines (inactivated) for veterinary use, a collaborative study was run as part of the EDQM Biological Standardisation Programme to establish BRP batch 5. Ten laboratories, including Official Medicines Control Laboratories and manufacturers, participated. The candidate BRP5 was assayed against the 6(th) International Standard for rabies vaccine using the in vivo vaccination-challenge assay (monograph 0451) to assign a potency value. The candidate was also compared to BRP batch 4 to establish continuity. Taking into account the results from the comparisons a potency of 10 IU/vial was assigned and in March 2015 the Ph. Eur. Commission adopted the material as Ph. Eur. BRP for rabies vaccines (inactivated) for veterinary use batch 5. In addition to the in vivo assay 3 laboratories tested the candidate material using their in-house in vitro assays for information.

[Vigilance for veterinary medicinal products: reports of adverse reactions in the year 2012]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2012.

197 adverse reactions of Swissmedic-authorized veterinary medicinal products were reported during the year 2012 (2011: 167). Species and drug classes remain unchanged over the years: most of the reports related to reactions following the use of antiparasitic products (37.6 %), antiinfectives (15.7 %) or non-steroidal antiinflammatory drugs (11.7 %) in companion animals (94 dogs and 53 cats) followed by cattle/calves (29). Additionally, 45 cases transmitted by the Swiss Toxicological Information Centre in Zürich were processed. We discuss a paradoxical reaction under the potential influence of acepromazine as well as a modified protocol for treating permethrin intoxication in cats. Finally, the vaccinovigilance program received 95 declarations following the application of various vaccines, mainly to dogs or cats.

En 2012, on a enregistré 197 annonces de réactions après application de médicaments vétérinaires autorisés par Swissmedic (2011: 167). La répartition de ces annonces, tant en ce qui concerne les espèces que les classes de médicaments, est inchangée par rapport aux années précédentes: on a annoncé le plus souvent des réactions à des produits antiparasitaires (37.6 %), antiinfectieux (15.7 %) ou antiinflammatoires (11.7 %) chez les petits animaux (94 annonces concernaient des chiens, 53 des chats) suivis par les bovins (29 annonces). En outre 45 cas annoncés par le Centre suisse d'information toxicologique de Zürich dans le cadre de ses activités de conseil ont été étudiés. Une réaction paradoxale d'agressivité sous l'effet possible de l'acépromazine et un protocole modifié pour le traitement des intoxications à la perméthrine chez le chat sont présentés. Pour ce qui est de la vaccinovigilance effectuée par l'IVI, on a enregistré 95 annonces de réactions après l'application de divers vaccins, principalement chez des chiens et des chats.

[Does emergency vaccination make sense as a supporting element in control of foot-and-mouth disease in Switzerland]. / Ist die Notimpfung als unterstützende Massnahme zur Tilgung der Maul- und Klauenseuche in der Schweiz sinnvoll?

The outbreak of foot and mouth disease (FMD) in Great Britain in 2001 let to discussions and especially emergency vaccination was deemed as an alternative to the culling of vast numbers of healthy animals. The project emergency vaccination for FMD in Switzerland was conducted to compare the effectiveness of conventional control strategies during a FMD outbreak alone and with ring vaccination of 3 km and 10 km, respectively. The results of this project showed that emergency vaccination conducted at the beginning of an epidemic was not favorable compared to conventional disease control strategy in Switzerland. In case of an advanced FMD epidemic, a 10 km ring vaccination could support the disease control in a positive way. However, the goal of emergency vaccination to save animal live can hardly be achieved due to actual legal basis and the consequent restriction measures within vaccination zones which will lead to welfare culling.

L'épizootie de fièvre aphteuse en Grande Bretagne en 2001 a montré que les abatages de masse d'animaux sains sont plus en plus critiquée. On discute régulièrement de la vaccination d'urgence comme mesure permettant de réduire le nombre d'animaux à tuer en cas d'épizootie. Dans le cadre du projet vaccination d'urgence FA suisse, on a comparé l'effet de la seule lutte conventionnelle avec celui d'une vaccination d'urgence «vaccination to live¼ dans un périmètre de 3 km (GV3) respectivement 10 km (GV10) quant à la durée et à l'importance du foyer. Au début d'une épizootie, la vaccination d'urgence supplémentaire n'apporte pas d'avantage face à la lutte conventionnelle. Si une vaccination V10 est pratiquée plus tardivement, elle peut dans certains cas amener une diminution et un raccourcissement de l'épizootie. Le but visant, grâce à la vaccination d'urgence, à tuer moins d'animaux ne peut toutefois pas, dans les conditions actuelles, être atteint car vu les fortes limitations du trafic d'animaux à l'intérieur des zones de vaccination, on doit compter avec des abattages pour des raisons de protections des animaux.

[Vigilance for veterinary medicinal products: reports of adverse reactions in the year 2011]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2011.

167 adverse reactions of Swissmedic-authorized veterinary medicinal products were reported during the year 2011 (2010: 160). Species and drug classes remain comparable with previous years: most of the reactions occurred following the use of antiparasitic products (39 %), antiinfectives (20 %) or non-steroidal antiinflammatory drugs (11 %) in companion animals (85 dogs and 27 cats) followed by cattle/calves (37). We received 15 cases of adverse reactions following reconverted use, 8 of them in treated cats. Additionally the Swiss Toxicological Information Centre in Zürich processed 84 enquiries and transmitted them to Swissmedic. One case of a successful new therapy to treat ivermectin poisoning in a pony is presented. Finally, the vaccinovigilance program received 60 declarations following the application of various vaccines, mainly to dogs or cats.

[Vigilance for veterinary medicinal products: declarations of adverse reactions in the year 2010]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2010.

In 2010, we observed again an increase in the number of declarations reported to the vigilance system for veterinary medicinal products up to a total of 160. The species and drug classes reported remained the same as in previous years: the majority of adverse drug reactions (ADRs) concerned either dogs or cats and the most frequently involved drugs were either antiparasitic products or antiinfectives. Adverse reactions following reconversions and 8 cases of suspected allergic reactions following the use of amoxicillin-clavulanic acid combinations in dogs were reported. Additional enquiries were processed by the Swiss Toxicological Information Centre and transmitted to Swiss medic. 11 of these reported accidental ingestions of flavoured tablets in overdose by dogs and some cats. The vaccino vigilance program received 179 declarations following immunization against blue tongue disease as well as 82 declarations following the application of other vaccines. The vigilance system increases the chance to identify rare reactions or interactions and thereby contributes to the security of veterinary medicinal products.

Collaborative study for validation of a serological potency assay for rabies vaccine (inactivated) for veterinary use.

European Pharmacopoeia (Ph. Eur.) monograph 0451 on Rabies vaccine (inactivated) for veterinary use describes an in vivo batch potency test that is based on the NIH test. This assay uses a large number of mice and results in a significant degree of suffering. In the interest of replacement, reduction and refinement of animal tests (3R) a serological potency assay for Rabies vaccine (inactivated) for animal use, developed and validated at the Paul-Ehrlich-Institut, has been assessed in a collaborative study organised by the EDQM (European Directorate for the Quality of Medicines & HealthCare). The goal was to demonstrate the wider transferability of the proposed assay and confirm its suitability. The study involved 13 laboratories and assessed 4 different vaccines from the EU market. Results of the study confirm that a limit test using a relatively small number of animals in a serological assay is possible, reproducible and reliable. The optimal number of animals per vaccine is product specific but may roughly be indicated to be between 8 and 10 for the products included in this study. Non-responders should be included in the analysis because they may reflect sub-potent vaccines. However, there may be a need to impose a maximum on the number of non-responders allowed for the reference vaccine as a monitor for assay validity. This assay provides a significant 3R improvement in terms of both the number of animals used and the amount of suffering entailed and provides a more reliable and reproducible assay format than the vaccination challenge assay. It also reduces the time required as compared to the vaccination challenge assay. It has been recommended to the Ph. Eur. group of experts 15V that this assay be included as an alternative to the batch potency assay in the Ph. Eur. monograph 0451.

[Vigilance for veterinary medicinal products: declarations of adverse reactions in the year 2009]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2009.

During the year 2009, 134 reports of suspected adverse drug reactions (ADRs) to veterinary medicinal products (VMPs) were received (106 in the year 2008). The distribution according to species and drug classes remained in line with previous years. Companion animals were involved in most of the reports (46 % dogs, 19 % cats), followed by cattle or calves (22 %). Antiparasitic drugs made the biggest part with 30 % of the reports, followed by antiinfectives (19 %) and hormones (13 %). Some reactions following their use are specifically discussed. 95 additional enquiries about ADRs of VMPs were received by the Swiss Toxicological Information Centre in Zürich. Most of them concerned dogs or cats and antiparasitics or anti-inflammatory drugs. In the vaccinovigilance program, a total of 1020 reports were received, of which 1000 were related to the vaccination against blue tongue disease. The most frequently reported adverse reactions were aborts, mastitis or alterations of milk quality and they are specifically discussed.

Humoral response to 2 inactivated bluetongue virus serotype-8 vaccines in South American camelids.

BACKGROUND: Bluetongue virus serotype 8 (BTV-8) has caused disease in domestic ruminants in several countries of northern Europe since 2006. In 2008 a mass-vaccination program was launched in most affected countries using whole virus inactivated vaccines. OBJECTIVE: To evaluate 2 inactivated vaccines (Bovilis BTV 8; BTVPUR AlSap8) for immunogenicity and safety against BTV-8 in South American camelids (SAC) in a field trial. ANIMALS: Forty-two SAC (25 Alpacas, 17 Llamas) aged between 1 and 16 years. METHODS: The animals were vaccinated twice at intervals of 21 days. They were observed clinically for adverse local, systemic, or both reactions throughout the trial. Blood samples collected on days 0, 14, 21, 43, and 156 after vaccination were tested for the presence of BTV-8 virus by real time-polymerase chain reaction and of specific antibodies by competitive ELISA and a serum neutralization test. RESULTS: All vaccinated animals developed antibodies to BTV-8 after the 2nd administration of the vaccine. No adverse effects were observed except for moderate local swellings at the injection site, which disappeared within 21 days. Slightly increased body temperatures were only observed in the first 2 days after vaccination. The BTV was not detected in any of the samples analyzed. CONCLUSIONS AND CLINICAL IMPORTANCE: The administration of the 2 inactivated commercial vaccines was safe and induced seroconversion against BTV-8 in all vaccinated animals. The results of this study suggest that 2 doses injected 3 weeks apart is a suitable vaccination regimen for SAC.

Viral safety and extraneous agents testing for veterinary vaccines: rationale for requirements, the European approach.

Freedom from extraneous agents is a high priority for any medicinal product. For veterinary vaccines, extraneous agents testing is addressed by different regulations of the European Pharmacopoeia and guidelines issued by the European Medicines Evaluation Agency. This article provides a brief review of the relevant texts.

Duration of protection in animals: the point of view of regulators.

In Europe, two main regulatory texts regulate the immunogenicity requirements of vaccines, the European Pharmacopoeia and the guidelines of the European Medicines Evaluation Agency (EMEA). This article outlines these requirements and the regulatory challenges.

[Vigilance for veterinary medicinal products: declarations of adverse reactions in the year 2008]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2008.

With 106 reports of suspected adverse reactions to veterinary medicinal products (VMPs) there was a slight decrease in the year 2008 compared to 2007. However, the distribution according to species and drug classes remained grossly the same: dogs were involved in 45 % of the cases followed in frequency by cats (26 %) and cows or calves (21 %). Most often the reports described reactions following the use of either an antiparasitic drug (46 %) or an antibiotic (22 %). One particular case of off-label use and serious skin reactions are presented. For the vaccinovigilance a total of 310 reports were received, with 250 of them related to adverse events following vaccination against blue tongue disease. In most cases, aborts and elevated cell count in the milk were reported. A detailed evaluation of these cases is presented. Finally, 305 enquiries were received by the Swiss Toxicological Information Center in Zürich (concerning mostly dogs or cats). Most of the cases concerned either preparations for the nervous system or anti-inflammatory drugs (human medicinal products) or antiparasitics (VMPs).

[Vaccination against bluetongue: safety and immune response in the field]. / Impfung gegen die Blauzungenkrankheit: Verträglichkeit und Immunantwort in der Praxis.

Bluetongue, caused by the bluetongue virus serotype 8 has rapidly spread through Europe since 2006. The first cases in Switzerland were detected in October 2007. The European Union and Switzerland launched a vaccination campaign in June 2008. This study aims to demonstrate the safety and the immune response of the three vaccines used in Switzerland under practical conditions in the field. The trial was carried out in cattle, sheep and goats. Based on the results of this study recommendations for the 2009 campaign are presented.

[Vigilance for veterinary medicinal products: declarations of suspected adverse reactions in the year 2007]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2007.

163 reports of suspected adverse reactions were received in the year 2007: 111 for veterinary medicinal (VMPs) and 52 for immunologic products. Half of the reported reactions for VMPs concerned either an antiparasitic drug (26%) or an antibiotic (24%). Reconversions (use in another target species or for another indication as registered) made the third most frequently mentioned group with 11 reports. For immunologicals, half of the declarations were related to an adverse reaction in dogs, the most frequently reported reaction in companion animals being allergies. Moreover, 272 enquiries were received by the Swiss Toxicological Information Center in Zürich. Most of these were related to dogs (73%) and the number of enquiries regarding VMPs correlated positively with the most frequently used therapeutic classes like antiparasitics (47%) and anti-inflammatory drugs (23%). The complexity of proscessing reports regarding the detection of residues in milk after prescribed withdrawal times is discussed in detail. In conclusion, the year 2007 is seen as a consolidation of the established system with a tendency towards increase in the number of complex cases.

Equine travellers to the Olympic Games in Hong Kong 2008: a review of worldwide challenges to equine health, with particular reference to vector-borne diseases.

The past 10-20 years have seen exponential growth in the volume of trade in horses and equine germplasm; and the extent of global horse movements has increased significantly in the last 4 years. In preparing for the transport of elite Olympic horses to Hong Kong in 2008, it will be very important to be as fully informed as possible of the disease situation in both the exporting and importing country, import and re-entry requirements, as well as having a vaccination strategy to protect against particular diseases. In this context the review describes the equine vector-borne disease situation in Europe, Asia, Africa and South America and provides estimates of the number of horse movements between these countries, as well as information on import requirements and vaccination strategies.

[Reported adverse reactions due to veterinary drugs in 2006]. / Gemeldete unerwünschte Wirkungen von Tierarzneimitteln im Jahr 2006.

We received 190 reports of suspected adverse events (SARs) following the use of veterinary drugs for the year 2006: 118 declarations for veterinary drugs and 72 declarations following the application of immunolgical medicinal products. Most of the 118 declarations relate to the use of antiparasitic drugs (48%) and every second declaration to drug use in dogs. Other drug classes concerned were, in decreasing order, antiinfectives (20%) and drugs used off-label (12%; other target species or other indication). For the vaccines, most of the reactions occurred in dogs (62%) followed by horses (11%) and cattle (10%). The most frequently reported reactions concerned the use of a vaccine against piroplasmosis. Another 349 requests for information were processed by the Swiss Toxicological Information center. We also present a case of a serious adverse reaction in form of a Stevens-Johnson syndrome in a cat as well as a case of ketamine abuse. We note the growing interest of practicing veterinarians with pleasure and are currently working on further adaptations to the system.