Skip to main content
Erschienen in: Neurotoxicity Research 3/2017

01.10.2017 | ORIGINAL ARTICLE

Methamidophos, an Organophosphorus Insecticide, Induces Pro-aggressive Behaviour in Mice

verfasst von: Cristina Paula do Nascimento, Gabriella Xavier Maretto, Graziany Leite Moreira Marques, Luciana Mesquita Passamani, Ana Paula Abdala, Luiz Carlos Schenberg, Vanessa Beijamini, Karla Nívea Sampaio

Erschienen in: Neurotoxicity Research | Ausgabe 3/2017

Einloggen, um Zugang zu erhalten

Abstract

Although evidence indicates that exposure to organophosphorus (OP) pesticides induces neurobehavioral disorders, little is known about the effects of OP on aggressive behaviour. Our study investigated the effects of repeated exposure to an OP pesticide, methamidophos, on the isolation-induced aggressive behaviour in mice. Forty seven male mice were individually housed for a month. Socially isolated animals were then confronted with a standard non-isolated opponent for 15 min (pre-treatment trial), and the latency and frequency of aggressive and general exploratory behaviours were recorded. Based on the presence of attack behaviour in the pre-treatment trial, mice were classified as isolation-induced aggressive and non-aggressive. All mice were then treated for 7 days with methamidophos (3.5 mg/kg/day, n = 22, intraperitoneal (i.p.)) or saline (1 mL/kg/day, control group, n = 25, i.p.), and a second trial was performed. Repeated exposure to methamidophos induced attack behaviour in non-aggressive mice. The treatment with methamidophos also decreased plasma butyrylcholinesterase and brain acetylcholinesterase activity. These results suggest that methamidophos has a pro-aggressive effect on socially isolated mice.
Literatur
Zurück zum Zitat Aldridge JE, Levin ED, Seidler FJ, Slotkin TA (2005) Developmental exposure of rats to chlorpyrifos leads to behavioral alterations in adulthood, involving serotonergic mechanisms and resembling animal models of depression. Environ Health Perspect 113:527–531. doi:10.1289/ehp.7867 CrossRefPubMedPubMedCentral Aldridge JE, Levin ED, Seidler FJ, Slotkin TA (2005) Developmental exposure of rats to chlorpyrifos leads to behavioral alterations in adulthood, involving serotonergic mechanisms and resembling animal models of depression. Environ Health Perspect 113:527–531. doi:10.​1289/​ehp.​7867 CrossRefPubMedPubMedCentral
Zurück zum Zitat Ali SF, Chandra O, Hasan M (1980) Effects of an organo-phosphate (dichlorvos) on open-field behavior and locomotor activity—correlation with regional brain monoamine levels. Psychopharmacology 68:37–42CrossRefPubMed Ali SF, Chandra O, Hasan M (1980) Effects of an organo-phosphate (dichlorvos) on open-field behavior and locomotor activity—correlation with regional brain monoamine levels. Psychopharmacology 68:37–42CrossRefPubMed
Zurück zum Zitat Allikmets L (1974) Cholinergic mechanisms in aggressive behaviour. Med Biol 51:19–30 Allikmets L (1974) Cholinergic mechanisms in aggressive behaviour. Med Biol 51:19–30
Zurück zum Zitat Allon N, Rabinovitz I, Manistersky E et al (2005) Acute and long-lasting cardiac changes following a single whole-body exposure to sarin vapor in rats. Toxicol Sci 87:385–390CrossRefPubMed Allon N, Rabinovitz I, Manistersky E et al (2005) Acute and long-lasting cardiac changes following a single whole-body exposure to sarin vapor in rats. Toxicol Sci 87:385–390CrossRefPubMed
Zurück zum Zitat Beleslin DB, Samardzić R (1979) Evidence of central cholinergic mechanisms in the appearance of affective aggressive behaviour: dissociation of aggression from autonomic and motor phenomena. Psychopharmacology 62:163–167. doi:10.1007/BF00427131 CrossRefPubMed Beleslin DB, Samardzić R (1979) Evidence of central cholinergic mechanisms in the appearance of affective aggressive behaviour: dissociation of aggression from autonomic and motor phenomena. Psychopharmacology 62:163–167. doi:10.​1007/​BF00427131 CrossRefPubMed
Zurück zum Zitat Bell R, Warburton DM, Brown K (1985) Drugs as research tools in psychology: cholinergic drugs and aggression. Neuropsychobiology 14:181–192CrossRefPubMed Bell R, Warburton DM, Brown K (1985) Drugs as research tools in psychology: cholinergic drugs and aggression. Neuropsychobiology 14:181–192CrossRefPubMed
Zurück zum Zitat Bouman WP, Pinner G (1998) Violent behavior-associated with donepezil. Am J Psychiatry 155:1626–1627CrossRefPubMed Bouman WP, Pinner G (1998) Violent behavior-associated with donepezil. Am J Psychiatry 155:1626–1627CrossRefPubMed
Zurück zum Zitat Brain P, Poole A (1974) Some studies on the use of “standard opponents” in intermale aggression testing in TT albino mice. Behaviour 53:539–548 Brain P, Poole A (1974) Some studies on the use of “standard opponents” in intermale aggression testing in TT albino mice. Behaviour 53:539–548
Zurück zum Zitat Brasil (1978) Portaria GM no 3.214, de 08 de junho de 1978. NR 7 -Programa de controle médico de saúde ocupacional. Diário Of da República Fed do Bras 1–16 Brasil (1978) Portaria GM no 3.214, de 08 de junho de 1978. NR 7 -Programa de controle médico de saúde ocupacional. Diário Of da República Fed do Bras 1–16
Zurück zum Zitat Caldas ED, De Souza MV, Jardim ANO (2011) Dietary risk assessment of organophosphorus and dithiocarbamate pesticides in a total diet study at a Brazilian university restaurant. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 28:71–79. doi:10.1080/19440049.2010.538935 CrossRefPubMed Caldas ED, De Souza MV, Jardim ANO (2011) Dietary risk assessment of organophosphorus and dithiocarbamate pesticides in a total diet study at a Brazilian university restaurant. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 28:71–79. doi:10.​1080/​19440049.​2010.​538935 CrossRefPubMed
Zurück zum Zitat Charpentier (1969) Analysis and measurement of aggression in mice. In: Aggressive behavior. pp 86–99 Charpentier (1969) Analysis and measurement of aggression in mice. In: Aggressive behavior. pp 86–99
Zurück zum Zitat Chen VP, Gao Y, Geng L et al (2015) Plasma butyrylcholinesterase regulates ghrelin to control aggression. Proc Natl Acad Sci 112:201421536 Chen VP, Gao Y, Geng L et al (2015) Plasma butyrylcholinesterase regulates ghrelin to control aggression. Proc Natl Acad Sci 112:201421536
Zurück zum Zitat Devinsky O, Kernan J, Bear DM (1992) Aggressive behavior following exposure to cholinesterase inhibitors. J Neuropsychiatry Clin Neurosci 4:189–194CrossRefPubMed Devinsky O, Kernan J, Bear DM (1992) Aggressive behavior following exposure to cholinesterase inhibitors. J Neuropsychiatry Clin Neurosci 4:189–194CrossRefPubMed
Zurück zum Zitat Dietz AA, Rubinstein HM, Lubrano T (1973) Colorimetric determination of serum cholinesterase and its genetic variants by the propionylthiocholine-dithiobis(nitrobenzoic acid)procedure. Clin Chem 19:1309–1313PubMed Dietz AA, Rubinstein HM, Lubrano T (1973) Colorimetric determination of serum cholinesterase and its genetic variants by the propionylthiocholine-dithiobis(nitrobenzoic acid)procedure. Clin Chem 19:1309–1313PubMed
Zurück zum Zitat Ecobichon DJ (2000) Our changing perspectives on benefits and risks of pesticides: a historical overview. Neurotoxicology 21:211–218PubMed Ecobichon DJ (2000) Our changing perspectives on benefits and risks of pesticides: a historical overview. Neurotoxicology 21:211–218PubMed
Zurück zum Zitat Ellman GL, Courtney KD, Andres VJ, Featherstone RM (1961) A new and rapid colorimetric of acetylcholinesterase determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95CrossRefPubMed Ellman GL, Courtney KD, Andres VJ, Featherstone RM (1961) A new and rapid colorimetric of acetylcholinesterase determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95CrossRefPubMed
Zurück zum Zitat Felip CM, Rodriguez-Arias M, Aguilar MA, Minarro J (2001) Antiaggressive and motor effects of the DA release inhibitor CGS 10746B. Aggress Behav 27:382–390. doi:10.1002/ab.1023 CrossRef Felip CM, Rodriguez-Arias M, Aguilar MA, Minarro J (2001) Antiaggressive and motor effects of the DA release inhibitor CGS 10746B. Aggress Behav 27:382–390. doi:10.​1002/​ab.​1023 CrossRef
Zurück zum Zitat Ferrer A (2003) Pesticide poisoning. An Sist Sanit Navar 26:1–2 Ferrer A (2003) Pesticide poisoning. An Sist Sanit Navar 26:1–2
Zurück zum Zitat Gray AJ (1982) Distribution and excretion of [ 14CH3S ] methamidophos after intravenous administration of a toxic dose and the relationship with anticholinesterase activity. Pestic Biochem Physiol 18:28–37CrossRef Gray AJ (1982) Distribution and excretion of [ 14CH3S ] methamidophos after intravenous administration of a toxic dose and the relationship with anticholinesterase activity. Pestic Biochem Physiol 18:28–37CrossRef
Zurück zum Zitat Gunnell D, Eddleston M, Phillips MR, Konradsen F (2007) The global distribution of fatal pesticide self-poisoning: systematic review. BMC Public Health 7:357CrossRefPubMedPubMedCentral Gunnell D, Eddleston M, Phillips MR, Konradsen F (2007) The global distribution of fatal pesticide self-poisoning: systematic review. BMC Public Health 7:357CrossRefPubMedPubMedCentral
Zurück zum Zitat Hsieh LS, Wen JH, Miyares L, Lombroso PJ, Bordey A (2017) Outbred CD1 mice are as suitable as inbred C57BL/6J mice in performing social tasks. Neuroscience Letters 637:142–147 Hsieh LS, Wen JH, Miyares L, Lombroso PJ, Bordey A (2017) Outbred CD1 mice are as suitable as inbred C57BL/6J mice in performing social tasks. Neuroscience Letters 637:142–147
Zurück zum Zitat Jeyaratnam J (1990) Acute pesticide poisoning: a major global health problem. World Health Stat Q 43:139–144PubMed Jeyaratnam J (1990) Acute pesticide poisoning: a major global health problem. World Health Stat Q 43:139–144PubMed
Zurück zum Zitat Lu JL (2010) Analysis of trends of the types of pesticide used, residues and related factors among farmers in the largest vegetable producing area in the Philippines. J Rural Med JRM / Japanese Assoc Rural Med 5:184–189. doi:10.2185/jrm.5.184 Lu JL (2010) Analysis of trends of the types of pesticide used, residues and related factors among farmers in the largest vegetable producing area in the Philippines. J Rural Med JRM / Japanese Assoc Rural Med 5:184–189. doi:10.​2185/​jrm.​5.​184
Zurück zum Zitat Mackenzie Ross S, McManus IC, Harrison V, Mason O (2013) Neurobehavioral problems following low-level exposure to organophosphate pesticides: a systematic and meta-analytic review. Crit Rev Toxicol 43:21–44. doi:10.3109/10408444.2012.738645 CrossRef Mackenzie Ross S, McManus IC, Harrison V, Mason O (2013) Neurobehavioral problems following low-level exposure to organophosphate pesticides: a systematic and meta-analytic review. Crit Rev Toxicol 43:21–44. doi:10.​3109/​10408444.​2012.​738645 CrossRef
Zurück zum Zitat Malick JB (1979) The pharmacology of isolation-induced aggressive behavior in mice. Curr Dev Psychopharmacol 5:1–27PubMed Malick JB (1979) The pharmacology of isolation-induced aggressive behavior in mice. Curr Dev Psychopharmacol 5:1–27PubMed
Zurück zum Zitat Miczek K (1983) Ethological analysis of drug action on aggression and defense. Prog Neuro-Psychopharmacol Biol Psychiatry 7:519–524CrossRef Miczek K (1983) Ethological analysis of drug action on aggression and defense. Prog Neuro-Psychopharmacol Biol Psychiatry 7:519–524CrossRef
Zurück zum Zitat Miczek KA, Fish EW, De Bold JF, De Almeida RM (2002) Social and neural determinants of aggressive behavior: pharmacotherapeutic targets at serotonin, dopamine and gama-aminobutyric acid systems. Psychopharmacology 163:434–458. doi:10.1007/s00213-002-1139-6 CrossRefPubMed Miczek KA, Fish EW, De Bold JF, De Almeida RM (2002) Social and neural determinants of aggressive behavior: pharmacotherapeutic targets at serotonin, dopamine and gama-aminobutyric acid systems. Psychopharmacology 163:434–458. doi:10.​1007/​s00213-002-1139-6 CrossRefPubMed
Zurück zum Zitat O’Malley M (1997) Clinical evaluation of pesticide exposure and poisonings. Lancet 349:1161–1166CrossRefPubMed O’Malley M (1997) Clinical evaluation of pesticide exposure and poisonings. Lancet 349:1161–1166CrossRefPubMed
Zurück zum Zitat Parmigiani S, Brain PF (1983) Effects of residence, aggressive experience and intruder familiarity on attack shown by male mice. Behav Process 8:45–57CrossRef Parmigiani S, Brain PF (1983) Effects of residence, aggressive experience and intruder familiarity on attack shown by male mice. Behav Process 8:45–57CrossRef
Zurück zum Zitat Peris-Sampedro F, Cabré M, Basaure P et al (2015) Adulthood dietary exposure to a common pesticide leads to an obese-like phenotype and a diabetic profile in apoE3 mice. Environ Res 142:169–176CrossRefPubMed Peris-Sampedro F, Cabré M, Basaure P et al (2015) Adulthood dietary exposure to a common pesticide leads to an obese-like phenotype and a diabetic profile in apoE3 mice. Environ Res 142:169–176CrossRefPubMed
Zurück zum Zitat Pires RGW, Pereira SRC, Oliveira-Silva IF et al (2005) Cholinergic parameters and the retrieval of learned and re-learned spatial information: a study using a model of Wernicke-Korsakoff syndrome. Behav Brain Res 162:11–21. doi:10.1016/j.bbr.2005.02.032 CrossRefPubMed Pires RGW, Pereira SRC, Oliveira-Silva IF et al (2005) Cholinergic parameters and the retrieval of learned and re-learned spatial information: a study using a model of Wernicke-Korsakoff syndrome. Behav Brain Res 162:11–21. doi:10.​1016/​j.​bbr.​2005.​02.​032 CrossRefPubMed
Zurück zum Zitat Pucilowski O, Eichelman B, Overstreet D et al (1990) Enhanced affective aggression in genetically bred hypercholinergic rats. Neuropsychobiology 91:37–41 Pucilowski O, Eichelman B, Overstreet D et al (1990) Enhanced affective aggression in genetically bred hypercholinergic rats. Neuropsychobiology 91:37–41
Zurück zum Zitat Ray A, Sen P, Alkondon M (1989) Biochemical and pharmacological evidence for central cholinergic regulation of shock-induced aggression in rats. Pharmacol Biochem Behav 32:867–871CrossRefPubMed Ray A, Sen P, Alkondon M (1989) Biochemical and pharmacological evidence for central cholinergic regulation of shock-induced aggression in rats. Pharmacol Biochem Behav 32:867–871CrossRefPubMed
Zurück zum Zitat Ricceri L, Venerosi A, Capone F et al (2006) Developmental neurotoxicity of organophosphorous pesticides: fetal and neonatal exposure to chlorpyrifos alters sex-specific behaviors at adulthood in mice. Toxicol Sci 93:105–113. doi:10.1093/toxsci/kfl032 CrossRefPubMed Ricceri L, Venerosi A, Capone F et al (2006) Developmental neurotoxicity of organophosphorous pesticides: fetal and neonatal exposure to chlorpyrifos alters sex-specific behaviors at adulthood in mice. Toxicol Sci 93:105–113. doi:10.​1093/​toxsci/​kfl032 CrossRefPubMed
Zurück zum Zitat Robinson CP, Beiergrohslein D (1982) Inhibition of human erythrocyte and plasma cholinesterases by methamidophos. J Appl Toxicol 2:217–218CrossRefPubMed Robinson CP, Beiergrohslein D (1982) Inhibition of human erythrocyte and plasma cholinesterases by methamidophos. J Appl Toxicol 2:217–218CrossRefPubMed
Zurück zum Zitat Rosenstock L, Keifer M, Daniell WE et al (1991) Chronic central nervous system effects of acute organophosphate pesticide intoxication. The Pesticide Health Effects Study Group Lancet 338:223–227 Rosenstock L, Keifer M, Daniell WE et al (1991) Chronic central nervous system effects of acute organophosphate pesticide intoxication. The Pesticide Health Effects Study Group Lancet 338:223–227
Zurück zum Zitat Sánchez C, Arnt J, Hyttel J, Moltzen EK (1993) The role of serotonergic mechanisms in inhibition of isolation-induced aggression in male mice. Psychopharmacology 110:53–59. doi:10.1007/BF02246950 CrossRefPubMed Sánchez C, Arnt J, Hyttel J, Moltzen EK (1993) The role of serotonergic mechanisms in inhibition of isolation-induced aggression in male mice. Psychopharmacology 110:53–59. doi:10.​1007/​BF02246950 CrossRefPubMed
Zurück zum Zitat Sánchez-Amate MC, Flores P, Sánchez-Santed F (2001a) Effects of chlorpyrifos in the plus-maze model of anxiety. Behav Pharmacol 12:285–292CrossRefPubMed Sánchez-Amate MC, Flores P, Sánchez-Santed F (2001a) Effects of chlorpyrifos in the plus-maze model of anxiety. Behav Pharmacol 12:285–292CrossRefPubMed
Zurück zum Zitat Savage EP, Keefe TJ, Mounce LM et al (1988) Chronic neurological sequelae of acute organophosphate pesticide poisoning. Arch Environ Heal An Int J 43:38–45CrossRef Savage EP, Keefe TJ, Mounce LM et al (1988) Chronic neurological sequelae of acute organophosphate pesticide poisoning. Arch Environ Heal An Int J 43:38–45CrossRef
Zurück zum Zitat Slotkin TA, Tate CA, Ryde IT et al (2006) Organophosphate insecticides target the serotonergic system in developing rat brain regions: disparate effects of diazinon and parathion at doses spanning the threshold for cholinesterase inhibition. Environ Health Perspect 114:1542–1546. doi:10.1289/ehp.9337 CrossRefPubMedPubMedCentral Slotkin TA, Tate CA, Ryde IT et al (2006) Organophosphate insecticides target the serotonergic system in developing rat brain regions: disparate effects of diazinon and parathion at doses spanning the threshold for cholinesterase inhibition. Environ Health Perspect 114:1542–1546. doi:10.​1289/​ehp.​9337 CrossRefPubMedPubMedCentral
Zurück zum Zitat Socko R, Gralewicz S, Gorny R (1999) Long-term behavioural effects of a repeated exposure to chlorphenvinphos in rats. Int J Occup Med Env Heal 12:105–117 Socko R, Gralewicz S, Gorny R (1999) Long-term behavioural effects of a repeated exposure to chlorphenvinphos in rats. Int J Occup Med Env Heal 12:105–117
Zurück zum Zitat Stallones L, Beseler C (2002) Pesticide poisoning and depressive symptoms among farm residents. Ann Epidemiol 12:389–394CrossRefPubMed Stallones L, Beseler C (2002) Pesticide poisoning and depressive symptoms among farm residents. Ann Epidemiol 12:389–394CrossRefPubMed
Zurück zum Zitat Sustková-Fiserová M, Vávrová J, Krsiak M (2009) Brain levels of GABA, glutamate and aspartate in sociable, aggressive and timid mice: an in vivo microdialysis study. Neuro Endocrinol Lett 30:79–84PubMed Sustková-Fiserová M, Vávrová J, Krsiak M (2009) Brain levels of GABA, glutamate and aspartate in sociable, aggressive and timid mice: an in vivo microdialysis study. Neuro Endocrinol Lett 30:79–84PubMed
Zurück zum Zitat van Erp AM, Miczek KA (2000) Aggressive behavior, increased accumbal dopamine, and decreased cortical serotonin in rats. J Neurosci 20:9320–9325PubMed van Erp AM, Miczek KA (2000) Aggressive behavior, increased accumbal dopamine, and decreased cortical serotonin in rats. J Neurosci 20:9320–9325PubMed
Zurück zum Zitat Wesseling C, De Joode BVW, Keifer M, et al (2010) Symptoms of psychological distress and suicidal ideation among banana workers with a history of poisoning by organophosphate or n-methyl carbamate pesticides 778–785. doi: 10.1136/oem.2009.047266 Wesseling C, De Joode BVW, Keifer M, et al (2010) Symptoms of psychological distress and suicidal ideation among banana workers with a history of poisoning by organophosphate or n-methyl carbamate pesticides 778–785. doi: 10.​1136/​oem.​2009.​047266
Zurück zum Zitat Yu B, Ding B, Shen H et al (2015) Analysis of reports of cases of pesticide poisoning in Jiangsu Province, China, from 2006 to 2013. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 33:194–198PubMed Yu B, Ding B, Shen H et al (2015) Analysis of reports of cases of pesticide poisoning in Jiangsu Province, China, from 2006 to 2013. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 33:194–198PubMed
Zurück zum Zitat Zivari-Rahman M, Lesani M, Shokouhi-Moqaddam S (2012) Comparison of mental health, aggression and hopefulness between student drug-users and healthy students (a study in Iran). Addict Heal 4:36–42 Zivari-Rahman M, Lesani M, Shokouhi-Moqaddam S (2012) Comparison of mental health, aggression and hopefulness between student drug-users and healthy students (a study in Iran). Addict Heal 4:36–42
Metadaten
Titel
Methamidophos, an Organophosphorus Insecticide, Induces Pro-aggressive Behaviour in Mice
verfasst von
Cristina Paula do Nascimento
Gabriella Xavier Maretto
Graziany Leite Moreira Marques
Luciana Mesquita Passamani
Ana Paula Abdala
Luiz Carlos Schenberg
Vanessa Beijamini
Karla Nívea Sampaio
Publikationsdatum
01.10.2017
Verlag
Springer US
Erschienen in
Neurotoxicity Research / Ausgabe 3/2017
Print ISSN: 1029-8428
Elektronische ISSN: 1476-3524
DOI
https://doi.org/10.1007/s12640-017-9750-9

Weitere Artikel der Ausgabe 3/2017

Neurotoxicity Research 3/2017 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Schützt Olivenöl vor dem Tod durch Demenz?

10.05.2024 Morbus Alzheimer Nachrichten

Konsumieren Menschen täglich 7 Gramm Olivenöl, ist ihr Risiko, an einer Demenz zu sterben, um mehr als ein Vierten reduziert – und dies weitgehend unabhängig von ihrer sonstigen Ernährung. Dafür sprechen Auswertungen zweier großer US-Studien.

Bluttest erkennt Parkinson schon zehn Jahre vor der Diagnose

10.05.2024 Parkinson-Krankheit Nachrichten

Ein Bluttest kann abnorm aggregiertes Alpha-Synuclein bei einigen Menschen schon zehn Jahre vor Beginn der motorischen Parkinsonsymptome nachweisen. Mit einem solchen Test lassen sich möglicherweise Prodromalstadien erfassen und die Betroffenen früher behandeln.

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Wartezeit nicht kürzer, aber Arbeit flexibler

Psychotherapie Medizin aktuell

Fünf Jahren nach der Neugestaltung der Psychotherapie-Richtlinie wurden jetzt die Effekte der vorgenommenen Änderungen ausgewertet. Das Hauptziel der Novellierung war eine kürzere Wartezeit auf Therapieplätze. Dieses Ziel wurde nicht erreicht, es gab jedoch positive Auswirkungen auf andere Bereiche.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.