Toxicology and the vulnerable brain

1995 ◽  
Vol 7 (1) ◽  
pp. 1-6 ◽  
Author(s):  
D.R.A. Uges
Keyword(s):  
The Netherlands ◽  
Forensic Toxicology ◽  
Symptomatic Treatment ◽  
Environmental Toxicology ◽  
Clinical Toxicology ◽  
Suicidal Attempt ◽  
Central Effects ◽  
The Past ◽  
Cardio Vascular ◽  
The Brain

SummaryToxicology is one of the eldest areas of special attention in medicine and pharmacy. In the past, forensic toxicology was the most important part, but nowadays, at least in the Netherlands, the clinical, occupational and environmental toxicology have the centre of attention.The brain plays its own role in the clinical toxicology. There the intoxication can take place, it can be the basis of the peripheral symptoms of the intoxication or it can be the cause of the intoxication, e.g. at a suicidal attempt or the hospital addiction syndrome.The somatic treatment of an intoxicated patient includes in the first place the stabilization of the patient (cardio-vascular, ventilation and central effects); then the removal of the poison from the surroundings and out of the patient by different suitable methods and finally the symptomatic treatment, sometimes with antidotes.In the Netherlands, hardly any intoxication is fatal, when the patient arrives in the hospital in time, or euthanasia took place on purpose.

Neuro-Clinical Signatures of Language Impairments: A Theoretical Framework for Function-to-structure Mapping in Clinics

2020 ◽  
Vol 20 (9) ◽  
pp. 800-811 ◽  
Author(s):  
Ferath Kherif ◽  
Sandrine Muller
Keyword(s):  
Brain Mapping ◽  
Theoretical Framework ◽  
Brain Regions ◽  
Language Impairments ◽  
Structure Mapping ◽  
Language Functions ◽  
The Past ◽  
Language Recovery ◽  
The Brain ◽  
Bow Tie

In the past decades, neuroscientists and clinicians have collected a considerable amount of data and drastically increased our knowledge about the mapping of language in the brain. The emerging picture from the accumulated knowledge is that there are complex and combinatorial relationships between language functions and anatomical brain regions. Understanding the underlying principles of this complex mapping is of paramount importance for the identification of the brain signature of language and Neuro-Clinical signatures that explain language impairments and predict language recovery after stroke. We review recent attempts to addresses this question of language-brain mapping. We introduce the different concepts of mapping (from diffeomorphic one-to-one mapping to many-to-many mapping). We build those different forms of mapping to derive a theoretical framework where the current principles of brain architectures including redundancy, degeneracy, pluri-potentiality and bow-tie network are described.

Chemo- and Optogenetic Strategies for the Elucidation of Pain Pathways

2019 ◽  
pp. 816-832 ◽  
Author(s):  
Sascha R. A. Alles ◽  
Anne-Marie Malfait ◽  
Richard J. Miller
Keyword(s):  
Chronic Pain ◽  
Pain Response ◽  
Conscious Perception ◽  
Novel Therapies ◽  
The Past ◽  
Nociceptive Pathways ◽  
Pain Pathways ◽  
Technical Advances ◽  
The Brain

Pain is not a simple phenomenon and, beyond its conscious perception, involves circuitry that allows the brain to provide an affective context for nociception, which can influence mood and memory. In the past decade, neurobiological techniques have been developed that allow investigators to elucidate the importance of particular groups of neurons in different aspects of the pain response, something that may have important translational implications for the development of novel therapies. Chemo- and optogenetics represent two of the most important technical advances of recent times for gaining understanding of physiological circuitry underlying complex behaviors. The use of these techniques for teasing out the role of neurons and glia in nociceptive pathways is a rapidly growing area of research. The major findings of studies focused on understanding circuitry involved in different aspects of nociception and pain are highlighted in this article. In addition, attention is drawn to the possibility of modification of chemo- and optogenetic techniques for use as potential therapies for treatment of chronic pain disorders in human patients.

Neuroimaging in Drug Discovery and Development: Paradigms for Accelerating New Drug Availability

2001 ◽  
Vol 14 (5) ◽  
pp. 407-415
Author(s):  
John T. Metz ◽  
Malcolm D. Cooper ◽  
Terry F. Brown ◽  
Leann H. Kinnunen ◽  
Declan J. Cooper
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Glucose Metabolism ◽  
Phase Ii ◽  
New Drugs ◽  
Central Effects ◽  
Drug Discovery And Development ◽  
Psychological Tasks ◽  
The Brain ◽  
Phase Iv

The process of discovering and developing new drugs is complicated. Neuroimaging methods can facilitate this process. An analysis of the conceptual bases and practical limitations of different neuroimaging modalities reveals that each technique can best address different kinds of questions. Radioligand studies are well suited to preclinical and Phase II questions when a compound is known or suspected to affect well-understood mechanisms; they are also useful in Phase IV to characterize effective agents. Cerebral blood flow studies can be extremely useful in evaluating the effects of a drug on psychological tasks (mostly in Phase IV). Glucose metabolism studies can answer the simplest questions about whether a compound affects the brain, where, and how much. Such studies are most useful in confirming central effects (preclinical and early clinical phases), in determining effective dose ranges (Phase II), and in comparing different drugs (Phase IV).

scholarly journals The evolution of trauma care in the Netherlands over 20 years

2019 ◽  
Vol 46 (2) ◽  
pp. 329-335 ◽  
Author(s):  
Falco Hietbrink ◽  
Roderick M. Houwert ◽  
Karlijn J. P. van Wessem ◽  
Rogier K. J. Simmermacher ◽  
Geertje A. M. Govaert ◽  
...  
Keyword(s):  
The Netherlands ◽  
Trauma Care ◽  
Trauma System ◽  
Trauma Surgeon ◽  
Severely Injured ◽  
Severely Injured Patients ◽  
The Past ◽  
Level 1 ◽  
Trauma Surgeons ◽  
Injured Patients

Abstract Introduction In 1999 an inclusive trauma system was initiated in the Netherlands and a nationwide trauma registry, including all admitted trauma patients to every hospital, was started. The Dutch trauma system is run by trauma surgeons who treat both the truncal (visceral) and extremity injuries (fractures). Materials and Methods In this comprehensive review based on previous published studies, data over the past 20 years from the central region of the Netherlands (Utrecht) was evaluated. Results It is demonstrated that the initiation of the trauma systems and the governance by the trauma surgeons led to a region-wide mortality reduction of 50% and a mortality reduction for the most severely injured of 75% in the level 1 trauma centre. Furthermore, major improvements were found in terms of efficiency, demonstrating the quality of the current system and its constructs such as the type of surgeon. Due to the major reduction in mortality over the past few years, the emphasis of trauma care evaluation shifts towards functional outcome of severely injured patients. For the upcoming years, centralisation of severely injured patients should also aim at the balance between skills in primary resuscitation and surgical stabilization versus longitudinal surgical involvement. Conclusion Further centralisation to a limited number of level 1 trauma centres in the Netherlands is necessary to consolidate experience and knowledge for the trauma surgeon. The future trauma surgeon, as specialist for injured patients, should be able to provide the vast majority of trauma care in this system. For the remaining part, intramural, regional and national collaboration is essential

scholarly journals DNA Methylation Profiles of Tph1A and BDNF in Gut and Brain of L. Rhamnosus-Treated Zebrafish

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 142
Author(s):  
Mariella Cuomo ◽  
Luca Borrelli ◽  
Rosa Della Monica ◽  
Lorena Coretti ◽  
Giulia De Riso ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
The Past ◽  
Targeted Analysis ◽  
Lack Of Information ◽  
High Resolution Power ◽  
Resolution Level ◽  
Health And Disease ◽  
High Doses ◽  
The Brain

The bidirectional microbiota–gut–brain axis has raised increasing interest over the past years in the context of health and disease, but there is a lack of information on molecular mechanisms underlying this connection. We hypothesized that change in microbiota composition may affect brain epigenetics leading to long-lasting effects on specific brain gene regulation. To test this hypothesis, we used Zebrafish (Danio Rerio) as a model system. As previously shown, treatment with high doses of probiotics can modulate behavior in Zebrafish, causing significant changes in the expression of some brain-relevant genes, such as BDNF and Tph1A. Using an ultra-deep targeted analysis, we investigated the methylation state of the BDNF and Tph1A promoter region in the brain and gut of probiotic-treated and untreated Zebrafishes. Thanks to the high resolution power of our analysis, we evaluated cell-to-cell methylation differences. At this resolution level, we found slight DNA methylation changes in probiotic-treated samples, likely related to a subgroup of brain and gut cells, and that specific DNA methylation signatures significantly correlated with specific behavioral scores.

scholarly journals The Resolution of International Commercial Disputes – What Role (if any) for Continental Europe?

AJIL Unbound ◽  
2021 ◽  
Vol 115 ◽  
pp. 11-16
Author(s):  
Giesela Rühl
Keyword(s):  
The Netherlands ◽  
Dispute Settlement ◽  
Middle Eastern ◽  
National Level ◽  
High Volume ◽  
Radical Change ◽  
The Past ◽  
The World ◽  
Traditional Market ◽  
Commercial Courts

The past sixteen years have witnessed the proliferation of international commercial courts around the world. However, up until recently, this was largely an Asian and a Middle Eastern phenomenon. Only during the past decade have Continental European countries, notably Germany, France and the Netherlands, joined the bandwagon and started to create new judicial bodies for international commercial cases. Driven by the desire to attract high-volume commercial litigation, these bodies try to offer international businesses a better dispute settlement framework. But what are their chances of success? Will more international litigants decide to settle their disputes in these countries? In this essay, I argue that, despite its recently displayed activism, Continental Europe lags behind on international commercial courts. In fact, although the various European initiatives are laudable, most cannot compete with the traditional market leaders, especially the London Commercial Court, or with new rivals in Asia and the Middle East. If Continental Europe wants a role in the international litigation market, it must embrace more radical change. And this change will most likely have to happen on the European––not the national––level.

scholarly journals The Microbiota–Gut–Brain Axis and Alzheimer Disease. From Dysbiosis to Neurodegeneration: Focus on the Central Nervous System Glial Cells

2021 ◽  
Vol 10 (11) ◽  
pp. 2358
Author(s):  
Maria Grazia Giovannini ◽  
Daniele Lana ◽  
Chiara Traini ◽  
Maria Giuliana Vannucchi
Keyword(s):  
Alzheimer Disease ◽  
Glial Cells ◽  
Cell Types ◽  
The Past ◽  
The Central Nervous System ◽  
Diseased State ◽  
The Brain ◽  
Alzheimer Disease Pathogenesis ◽  
Brain Homeostasis

The microbiota–gut system can be thought of as a single unit that interacts with the brain via the “two-way” microbiota–gut–brain axis. Through this axis, a constant interplay mediated by the several products originating from the microbiota guarantees the physiological development and shaping of the gut and the brain. In the present review will be described the modalities through which the microbiota and gut control each other, and the main microbiota products conditioning both local and brain homeostasis. Much evidence has accumulated over the past decade in favor of a significant association between dysbiosis, neuroinflammation and neurodegeneration. Presently, the pathogenetic mechanisms triggered by molecules produced by the altered microbiota, also responsible for the onset and evolution of Alzheimer disease, will be described. Our attention will be focused on the role of astrocytes and microglia. Numerous studies have progressively demonstrated how these glial cells are important to ensure an adequate environment for neuronal activity in healthy conditions. Furthermore, it is becoming evident how both cell types can mediate the onset of neuroinflammation and lead to neurodegeneration when subjected to pathological stimuli. Based on this information, the role of the major microbiota products in shifting the activation profiles of astrocytes and microglia from a healthy to a diseased state will be discussed, focusing on Alzheimer disease pathogenesis.

scholarly journals Proteomic insights into synaptic signaling in the brain: the past, present and future

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yalan Xu ◽  
Xiuyue Song ◽  
Dong Wang ◽  
Yin Wang ◽  
Peifeng Li ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Protein Complexes ◽  
Synaptic Signaling ◽  
Brain Functions ◽  
The Past ◽  
Data Independent Acquisition ◽  
Technological Advances ◽  
Neural Communication ◽  
Chemical Synapses ◽  
The Brain

AbstractChemical synapses in the brain connect neurons to form neural circuits, providing the structural and functional bases for neural communication. Disrupted synaptic signaling is closely related to a variety of neurological and psychiatric disorders. In the past two decades, proteomics has blossomed as a versatile tool in biological and biomedical research, rendering a wealth of information toward decoding the molecular machinery of life. There is enormous interest in employing proteomic approaches for the study of synapses, and substantial progress has been made. Here, we review the findings of proteomic studies of chemical synapses in the brain, with special attention paid to the key players in synaptic signaling, i.e., the synaptic protein complexes and their post-translational modifications. Looking toward the future, we discuss the technological advances in proteomics such as data-independent acquisition mass spectrometry (DIA-MS), cross-linking in combination with mass spectrometry (CXMS), and proximity proteomics, along with their potential to untangle the mystery of how the brain functions at the molecular level. Last but not least, we introduce the newly developed synaptomic methods. These methods and their successful applications marked the beginnings of the synaptomics era.

Editorial

2016 ◽  
Vol 15 (1) ◽  
pp. 2-2
Author(s):  
Chris Roseveare ◽  
Keyword(s):  
The Netherlands ◽  
Editorial Team ◽  
Patient Specific ◽  
Service Improvement ◽  
Single Individual ◽  
National Goal ◽  
Acute Medicine ◽  
North West ◽  
The Past

Clinicians working in acute medicine will be familiar with change. The speciality and the environment we work in has changed continually over the past 15 years – I often reflect that no two years have been the same since I started working in the field back in 1999. Change is important, in order to achieve best practice, but sustaining such improvements can be an enormous challenge. The regular turnover of medical staff, local management restructuring and the constantly shifting National goal posts often conspire against us. It is easy for ‘changefatigue’ to set in. Submissions to this journal often describe local audits and service improvement projects which have raised standards: a low baseline may result in a statistically significant improvement from a relatively small intervention – often an education programme or poster campaign to raise awareness of the problem. However, what happens next is far more important: can the improvement be sustained when the key driver behind the project – the enthusiast – moves on, after their 4 month block of acute medicine comes to an end? One year on, we are often back where we started. Two articles in this edition appear to have achieved the Holy Grail of sustainability. In the paper by Joanne Botten from Musgrove Park, door to antibiotic time was improved for patients with neutopaenic sepsis by introducing a system whereby the antibiotics could be administered without waiting for a prescription to be written. The combination of a neutropaenic sepsis alert card and a patient-specific direction empowered the nurses and patients to ensure administration within an hour of arrival in over 90% of cases, a figure which has been sustained for over a year. Sustainable change is often facilitated by modifications in paperwork, but crucially the project’s success was not reliant on a single individual. The value of engaging with the wider team is also shown in Gary Misselbook’s paper describing sustained improvement in the layout and utility of an AMU procedure room. The authors describe how repeated attempts by different registrars had failed to achieve more than temporary reorganisation; the change was only sustained when nursing, infection control and administrative staff became involved in the process. The multiprofessional nature of the AMU is one of its greatest assets – we would all do well to remember this when instigating change. On a similar note, observant readers may have noticed some changes to the editorial board of this journal – I am delighted to welcome Dr Tim Cooksley, acute physician from Manchester and Dr Prabath Nanayakkara from the VUMC in the Netherlands. Tim came through the acute medicine training programme in the North West and his role in the acute oncology service at the Christie Hospital as well as his active involvement in the SAMBA project over recent years brings an important perspective to the editorial team. Prabath has been heavily involved with the development of acute medicine in the Netherlands and co-hosted the successful SAMSTERDAM meeting in 2014. His international perspective will be welcome as we attempt to extend the reach of Acute Medicine to our European neighbours over the coming years. I am very grateful to Nik Patel, Mark Jackson and Ashwin Pinto for their help and support during the past decade and wish them well for the future.

Sign in / Sign up

Export Citation Format

Share Document