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1.
Travel Med Infect Dis ; 46: 102275, 2022.
Article in English | MEDLINE | ID: mdl-35131427

ABSTRACT

BACKGROUND: Humanitarian disaster environments put relief workers at risk, both physically and mentally. Research looking at the growing humanitarian workforce's health and working conditions is lacking. METHODS: A questionnaire was presented to ICRC (International Committee of the Red Cross) workers during debriefing between 2016 and 2018. Participants were queried about their experience abroad including security incidents (the primary objective), health, and malaria prevention. Descriptive statistics and multivariate logistic regressions were used for data analysis. RESULTS: Security incidents were reported by 12% (95/796) of expatriates, mainly armed threats and attacks (83%, 79/95). Accidents or injuries occurred for 7.5% (60/796), of which 42% (25/60) were due to sporting activities and 22% (13/60) to road accidents. Many engaged in risky behaviours (15%, 119/795), such as driving too fast or inebriated (37%, 44/119) and/or engaging in unsafe sex, (unfamiliar partner, no condom) (71%; 84/119). Compliance to malaria prophylaxis was low 43% (113/263). Over 40% (324/795) found the mission more stressful than expected. Almost a third (28%, 219/796) reported worsened health on their return. CONCLUSIONS: Humanitarian aid workers display a worsening of their health when on mission due to violence, accidents and risky behaviours. To preserve their staff's wellbeing, humanitarian organizations should pay attention to medical history, pre-travel training specific to assignment, and continuous medical and psychological support.


Subject(s)
Disasters , Relief Work , Condoms , Humans , Red Cross , Violence
2.
Equine Vet J ; 50(5): 644-648, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29330860

ABSTRACT

BACKGROUND: Sudden death affects the health of horses, the safety of riders and the public perception of animal welfare during equestrian events. OBJECTIVES: To describe the signalment, clinical history, sudden death episode, rider injuries and causes of sudden death during exercise or closely thereafter in sport and pleasure riding horses. STUDY DESIGN: Retrospective case series based on an online questionnaire. METHODS: An online questionnaire was distributed to the veterinary and equestrian community. Connections of animals reported in the press to have died suddenly were sent the survey. Responses were analysed to obtain information. RESULTS: Fifty-seven cases met inclusion criteria with enough information to be analysed. The most common discipline was eventing (n = 23, 40.4%), and the most common breed involved was Thoroughbred (n = 23, 40.4%). Forty-one (71.9%) horses collapsed during exercise, and 16 (28.1%) shortly thereafter. Twenty-four (42.1%) horses died during or near the time of competition and 33 (57.9%) during or near the time of training or a pleasure ride. In 16 (28.1%) horses, the cause of death was known or strongly suspected based on a post-mortem result, and a cardiovascular origin was reported in 13 of these 16 cases. Riders were injured in 13 (22.8%) cases, and injuries to their extremities were the most frequent. MAIN LIMITATIONS: There is potential for misdiagnosis and recall and selection bias, and in the absence of data on the total number of horses engaged in equestrian sports and riding, prevalence cannot be calculated. CONCLUSIONS: Sudden death occurred in many types of equestrian sports and in riding horses. Death outside competition was more common suggesting that registries based on reports from official veterinarians underestimate the magnitude of this problem. Rider injuries were not uncommon when ridden horses collapsed and died. A definitive diagnosis for the cause of death was not commonly achieved and cardiovascular origin was the most common where a diagnosis was proposed by survey respondents.


Subject(s)
Cardiovascular Diseases/veterinary , Death, Sudden/veterinary , Horse Diseases/mortality , Physical Conditioning, Animal , Animals , Cardiovascular Diseases/mortality , Data Collection , Horses , Humans , Retrospective Studies , Risk Factors , Surveys and Questionnaires , Wounds and Injuries
3.
Rev Med Suisse ; 10(429): 997-1000, 2014 May 07.
Article in French | MEDLINE | ID: mdl-24908742

ABSTRACT

During a stay abroad, travelers are exposed to dangers and threats. This is nothing new, and most of the risks (e.g. traffic accidents) remain the same for many years. Large territories have nonetheless become inaccessible due to political instability, national or international conflicts, terrorist threat, or kidnapping risk. It is thus necessary to consider the problematic of security, whether at the time of preparation or at the destination. Beyond the usual pre-departure health counseling, the primary care physician may have a role to accompany the traveller in the management of his or her security. The aim should be to make travelers conscious of hazards and direct him or her towards available resources for planning, decision making support, and implementation of risk mitigation measures.


Subject(s)
Public Health , Safety , Travel Medicine/standards , Accidents, Traffic/prevention & control , Accidents, Traffic/statistics & numerical data , Humans , Information Dissemination , Patient Acceptance of Health Care , Public Health/methods , Public Health/standards , Safety/standards , Travel/statistics & numerical data
4.
Schweiz Arch Tierheilkd ; 155(11): 613-20, 2013 Nov.
Article in German | MEDLINE | ID: mdl-24168771

ABSTRACT

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.


Subject(s)
Adverse Drug Reaction Reporting Systems/statistics & numerical data , Veterinary Drugs/adverse effects , Acepromazine/adverse effects , Adverse Drug Reaction Reporting Systems/standards , Animals , Anti-Infective Agents/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Antiparasitic Agents/adverse effects , Cat Diseases/chemically induced , Cat Diseases/therapy , Cats , Cattle , Dogs , Dopamine Antagonists/adverse effects , Insecticides/poisoning , Permethrin/poisoning , Poisoning/therapy , Poisoning/veterinary , Switzerland , Vaccines/adverse effects
5.
Schweiz Arch Tierheilkd ; 154(12): 513-9, 2012 Dec.
Article in German | MEDLINE | ID: mdl-23188763

ABSTRACT

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.


Subject(s)
Anti-Infective Agents/adverse effects , Veterinary Drugs/adverse effects , Adverse Drug Reaction Reporting Systems , Animals , Animals, Domestic , Cats , Cattle , Dogs , Horses , Switzerland
7.
Schweiz Arch Tierheilkd ; 154(2): 57-65, 2012 Feb.
Article in German | MEDLINE | ID: mdl-22287137

ABSTRACT

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.


Subject(s)
Adverse Drug Reaction Reporting Systems , Drug-Related Side Effects and Adverse Reactions/veterinary , Veterinary Drugs/adverse effects , Animals , Bluetongue/prevention & control , Cats , Dogs , Product Surveillance, Postmarketing , Switzerland , Vaccines/adverse effects
8.
Sci Rep ; 1: 119, 2011.
Article in English | MEDLINE | ID: mdl-22355636

ABSTRACT

We describe a previously unknown assemblage of seamount-associated megabenthos that has by far the highest peak biomass reported in the deep-sea outside of vent communities. The assemblage was found at depths of 2-2.5 km on rocky geomorphic features off the southeast coast of Australia, in an area near the Sub-Antarctic Zone characterised by high rates of surface productivity and carbon export to the deep-ocean. These conditions, and the taxa in the assemblage, are widely distributed around the Southern mid-latitudes, suggesting the high-biomass assemblage is also likely to be widespread. The role of this assemblage in regional ecosystem and carbon dynamics and its sensitivities to anthropogenic impacts are unknown. The discovery highlights the lack of information on deep-sea biota worldwide and the potential for unanticipated impacts of deep-sea exploitation.


Subject(s)
Aquatic Organisms , Biomass , Ecosystem , Oceans and Seas , Animals , Anthozoa , Sea Anemones , Tasmania , Thoracica
9.
Schweiz Arch Tierheilkd ; 152(12): 575-83, 2010 Dec.
Article in German | MEDLINE | ID: mdl-21104632

ABSTRACT

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.


Subject(s)
Veterinary Drugs/standards , Abortion, Induced/veterinary , Animals , Animals, Domestic , Antiparasitic Agents/standards , Cats , Cattle , Dogs , Female , Milk/standards , Pregnancy , Switzerland , Vaccines/adverse effects , Vaccines/classification , Vaccines/standards , Veterinary Drugs/adverse effects , Veterinary Drugs/classification
10.
Schweiz Arch Tierheilkd ; 151(12): 583-90, 2009 Dec.
Article in German | MEDLINE | ID: mdl-19946849

ABSTRACT

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).


Subject(s)
Animal Diseases/drug therapy , Veterinary Drugs/therapeutic use , Animal Diseases/immunology , Animals , Cat Diseases/drug therapy , Cat Diseases/immunology , Cats , Cattle , Cattle Diseases/drug therapy , Cattle Diseases/immunology , Dog Diseases/drug therapy , Dog Diseases/immunology , Dogs , Veterinary Drugs/adverse effects
11.
Schweiz Arch Tierheilkd ; 151(1): 12-20, 2009 Jan.
Article in German | MEDLINE | ID: mdl-19160166

ABSTRACT

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.


Subject(s)
Vaccines/adverse effects , Veterinary Drugs/adverse effects , Veterinary Medicine/standards , Adverse Drug Reaction Reporting Systems , Animals , Animals, Domestic , Product Surveillance, Postmarketing , Switzerland
12.
Cell Mol Life Sci ; 65(4): 644-55, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18202825

ABSTRACT

Poly(ADP-ribose) (PAR) has been identified as a DNA damage-inducible cell death signal upstream of apoptosis-inducing factor (AIF). PAR causes the translocation of AIF from mitochondria to the nucleus and triggers cell death. In living cells, PAR molecules are subject to dynamic changes pending on internal and external stress factors. Using RNA interference (RNAi), we determined the roles of poly(ADP-ribose) polymerases-1 and -2 (PARP-1, PARP-2) and poly(ADP-ribose) glycohydrolase (PARG), the key enzymes configuring PAR molecules, in cell death induced by an alkylating agent. We found that PARP-1, but not PARP-2 and PARG, contributed to alkylation-induced cell death. Likewise, AIF translocation was only affected by PARP-1. PARP-1 seems to play a major role configuring PAR as a death signal involving AIF translocation regardless of the death pathway involved.


Subject(s)
Cell Death/physiology , Poly Adenosine Diphosphate Ribose/metabolism , Poly(ADP-ribose) Polymerases/metabolism , Alkylation , Animals , Apoptosis/physiology , DNA Damage , Fibroblasts/enzymology , HeLa Cells , Humans , Kinetics , Mice , Poly(ADP-ribose) Polymerases/genetics , Polymerase Chain Reaction , RNA, Small Interfering/genetics
13.
Schweiz Arch Tierheilkd ; 149(10): 439-48, 2007 Oct.
Article in German | MEDLINE | ID: mdl-17983016

ABSTRACT

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.


Subject(s)
Adverse Drug Reaction Reporting Systems , Product Surveillance, Postmarketing , Vaccines/adverse effects , Veterinary Drugs/adverse effects , Veterinary Medicine/standards , Animals , Animals, Domestic , Switzerland
14.
Schweiz Arch Tierheilkd ; 149(2): 57-63, 2007 Feb.
Article in German | MEDLINE | ID: mdl-17343131

ABSTRACT

We received 105 reports of suspected adverse events (SARs) following the use of veterinary drugs for the year 2005. This corresponds to a 35% increase compared to 2004. Practicing veterinarians sent most of these declarations. 73% of these concerned drugs used on companion animals. Antiparasitic drugs approved for topical use were the most frequently represented group with 48%, followed by drugs used to treat gastrointestinal disorders (11%) and drugs used off-label (14%; other target species or other indication). For the first time 2 declarations concerning the application of permethrin containing spot-on preparations used by mistake on cats were received. An overview of 20 declarations about adverse reactions following application of different vaccines is also presented with emphasis on the problem of fibrosarcoma in cats. We are pleased by the growing interest shown by practicing veterinarians for the vigilance system and hope to further develop this collaboration in the future.


Subject(s)
Adverse Drug Reaction Reporting Systems , Product Surveillance, Postmarketing , Vaccines/adverse effects , Veterinary Drugs/adverse effects , Veterinary Medicine/standards , Animals , Animals, Domestic , Registries , Switzerland
15.
Schweiz Arch Tierheilkd ; 148(8): 397-400, 402-4, 2006 Aug.
Article in German | MEDLINE | ID: mdl-16933703

ABSTRACT

The new Swiss ordinance on veterinary drugs poses a new challenge to the veterinarians, specially those working with farm animals. A complete overview about the registered veterinary drugs and immunobiologicals is absolutely necessary to cope with these new tasks: the internet version of the Swiss Veterinary Drug Compendium is a versatile tool to satisfy this needs (http://www.tierarzneimittel.ch). Due to the frequent updates and powerful search possibilities, this database is a reliable and comprehensive information system regarding Swiss veterinary drugs. We will demonstrate how this system can be used as a valuable help in the case of reconversions of drugs (e.g. use of small animal drugs in farm animals).


Subject(s)
Legislation, Drug , Legislation, Veterinary , Safety , Veterinary Drugs/standards , Animals , Switzerland
16.
Schweiz Arch Tierheilkd ; 147(7): 304-10, 2005 Jul.
Article in German | MEDLINE | ID: mdl-16041977

ABSTRACT

We received 62 reports of suspected adverse events (SARs) for the year 2004. Their number and repartition according to affected animals and active substances were comparable with the previous year. The distributors or manufacturers submitted most of the declarations, but the proportion submitted by practicing veterinarians is slowly growing. 72% of the declarations dealt with adverse reactions in small animals (cats and dogs), followed by cattle and horses. Antiparasitics, anti-inflammatory drugs and immunologicals were the most frequently mentioned therapeutic classes, which are listed here according to the international ATCvet classification. A report from abroad about a fatality following injection of an antibiotic preparation for cattle prompted Swissmedic to review the security of this medication also sold on the Swiss market. It was decided to modify the package insert to warn about the danger of inadvertent self-injection in humans, to reduce the risk of similar accidents in Switzerland. We hope that the pharmacovigilance system will enjoy an increasing awareness by the practicing veterinarians.


Subject(s)
Adverse Drug Reaction Reporting Systems , Product Surveillance, Postmarketing , Veterinary Drugs/adverse effects , Veterinary Medicine/standards , Animals , Animals, Domestic , Anti-Inflammatory Agents/adverse effects , Anti-Inflammatory Agents/therapeutic use , Antiparasitic Agents/adverse effects , Antiparasitic Agents/therapeutic use , Switzerland , Veterinary Drugs/therapeutic use
17.
Schweiz Arch Tierheilkd ; 146(11): 499-505, 2004 Nov.
Article in German | MEDLINE | ID: mdl-15581284

ABSTRACT

Pharmacovigilance is a system concerned with the acquisition, evaluation and classification of informations about suspected adverse drug reactions (SADR). Such a system was developed in Switzerland under the supervision of Swissmedic after the introduction of the federal law on therapeutic products on January 1st 2002. By sending declarations about SADRs, veterinary practitioners play a central role in this scheme. The reports are processed according to international standards (ABON) and provide useful hints to enhance the safety of drug usage by both patients and owners. The system acquired 58 reports in its first complete year of operation (2003). Analysis of these reveals that trends observed in foreign countries are also applicable to Switzerland: most of the reports concerned the use of antiparasitic or antibiotic drugs in small animals. The first year also revealed a high percentage of declarations coming from the pharmaceutical companies and the authors would therefore like to encourage practitioners to take a more active part in this scheme.


Subject(s)
Adverse Drug Reaction Reporting Systems , Veterinary Drugs/adverse effects , Veterinary Medicine/standards , Animals , Animals, Domestic , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Antiparasitic Agents/adverse effects , Antiparasitic Agents/therapeutic use , Product Surveillance, Postmarketing , Switzerland
18.
Schweiz Arch Tierheilkd ; 146(3): 127-34, 2004 Mar.
Article in German | MEDLINE | ID: mdl-15060977

ABSTRACT

Because cases of poisoning are observed rarely, veterinary practitioners have only limited knowledge of clinical toxicology and may face considerable problems in handling toxicological emergencies. In this report, we describe a novel decision support system for the management of poisonings in companion animals that provides rapid access to the current knowledge of clinical toxicology. For that purpose, relevant reports from the peer-reviewed literature were evaluated and organised according to the requirements of a structured database. The information provided for each toxic substance includes a summary of its chemical and physical properties, sources, commercial uses or natural occurrences, toxicokinetic data, mechanisms of action, threshold doses, clinical symptoms with brief case reports, sampling and analytical results, post-mortem findings, differential diagnoses, therapeutic guidelines and references to the literature. This decision support system has been programmed with two user-friendly search functions: a search tool that allows to choose clinical symptoms, and another function that serves to find a substance using its chemical name, the class of compounds to wich it belongs, a possible source or one of its main applications. CliniTox can be accessed directly via our webserver (http://www.clinitox.ch).


Subject(s)
Animals, Domestic , Databases, Factual , Internet , Poisoning/veterinary , Animals , Plants, Toxic/poisoning , Poison Control Centers , Poisoning/therapy , Switzerland , Toxicology/statistics & numerical data
19.
Int J Radiat Biol ; 78(6): 527-34, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12065056

ABSTRACT

PURPOSE: To characterize the response to X-irradiation of the poly ADP-ribosylation system in two closely related murine lymphoma sublines, L5178Y-R (LY-R) and L5178Y-S (LY-S), with differential sensitivity to various DNA damaging agents (UV-C and ionizing radiation, hydrogen peroxide). MATERIALS AND METHODS: LY cells were X-irradiated (2 Gy). NAD+ was determined in cell extracts by high-pressure liquid chromatography. ADP-ribose polymers were purified and analysed by densitometry after polyacrylamide gel electrophoresis. Nuclear matrix proteins were separated by SDS-polyacrylamide gel electrophoresis and processed for ADP-ribose polymer blots to estimate their ability to bind poly(ADP-ribose). RESULTS: In the radiosensitive LY-S cells, the constitutive levels of ADP-ribose polymers were twofold higher than in radioresistant LY-R cells, but unresponsive to a challenge with 2 Gy X-rays. The concentrations of NAD+ - the substrate for poly(ADP-ribose) synthesis - were identical in the two cell lines. X-rays (2 Gy) depleted NAD+ only in LY-S cells. These cells also produced shorter poly(ADP-ribose) molecules as compared with LY-R cells. Nuclear matrix preparations of LY-S cells exhibited lower poly(ADP-ribose)-binding capacity than those of LY-R cells. CONCLUSION: The results demonstrate disturbances in the poly ADP-ribosylation response of the radiosensitive LY-S cells and reduced poly(ADP-ribose)-binding affinity of the nuclear matrix of these cells.


Subject(s)
Leukemia L5178/metabolism , Leukemia L5178/radiotherapy , Poly Adenosine Diphosphate Ribose/metabolism , Poly Adenosine Diphosphate Ribose/radiation effects , Animals , DNA Damage , DNA Repair , Hydrogen Peroxide/pharmacology , Mice , NAD/metabolism , NAD/radiation effects , Nuclear Matrix/drug effects , Nuclear Matrix/metabolism , Nuclear Matrix/radiation effects , Radiation Tolerance , Signal Transduction/radiation effects , Tumor Cells, Cultured , Ultraviolet Rays
20.
J Biol Chem ; 275(52): 40974-80, 2000 Dec 29.
Article in English | MEDLINE | ID: mdl-11016934

ABSTRACT

Poly(ADP-ribose) is formed in possibly all multicellular organisms by a familiy of poly(ADP-ribose) polymerases (PARPs). PARP-1, the best understood and until recently the only known member of this family, is a DNA damage signal protein catalyzing its automodification with multiple, variably sized ADP-ribose polymers that may contain up to 200 residues and several branching points. Through these polymers, PARP-1 can interact noncovalently with other proteins and alter their functions. Here we report the discovery of a poly(ADP-ribose)-binding sequence motif in several important DNA damage checkpoint proteins. The 20-amino acid motif contains two conserved regions: (i) a cluster rich in basic amino acids and (ii) a pattern of hydrophobic amino acids interspersed with basic residues. Using a combination of alanine scanning, polymer blot analysis, and photoaffinity labeling, we have identified poly(ADP-ribose)-binding sites in the following proteins: p53, p21(CIP1/WAF1), xeroderma pigmentosum group A complementing protein, MSH6, DNA ligase III, XRCC1, DNA polymerase epsilon, DNA-PK(CS), Ku70, NF-kappaB, inducible nitric-oxide synthase, caspase-activated DNase, and telomerase. The poly(ADP-ribose)-binding motif was found to overlap with five important functional domains responsible for (i) protein-protein interactions, (ii) DNA binding, (iii) nuclear localization, (iv) nuclear export, and (v) protein degradation. Thus, PARPs may target specific signal network proteins via poly(ADP-ribose) and regulate their domain functions.


Subject(s)
Carrier Proteins/analysis , DNA Damage , DNA-Binding Proteins , Poly Adenosine Diphosphate Ribose/metabolism , Alanine , Amino Acid Motifs , Amino Acid Sequence , Binding Sites , Carrier Proteins/chemistry , Carrier Proteins/metabolism , DNA Repair , DNA-Activated Protein Kinase , Molecular Sequence Data , Protein Serine-Threonine Kinases/physiology
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