Case report: Acute unintentional carbachol intoxication

INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure

The Blooming of the Self on the Skin: reflections on tattoos and visibility regimes

Este artigo propõe uma discussão acerca das intervenções no corpo humano pela perspectiva do consumo, comunicação e psicanálise. Como objeto de estudo, as tatuagens são fenômenos férteis para pensar limites e configurações de regimes de visibilidade contemporâneos. Em particular, investigaremos intervenções estéticas em cicatrizes como tentativas de ressignificação e expressão corporal através do programa BBC Three: A Tattoo To Change Your Life. A produção de novos sentidos através de tais inscrições na pele manifesta a celebração de um compromisso moral de um dever-ser, fundamentado na condição corpórea como subterfúgio para construção e reconhecimento de subjetividades. This article aims to discuss interventions in the human body from the perspective of communication, consumption and psychoanalysis. Tattoos are fertile phenomena for revisiting the limits and configurations of contemporary visibility regimes. In particular, we investigated aesthetic interventions over scars as attempts at resignification and corporal expression through the BBC Three program: A Tattoo To Change Your Life. The production of meanings through such inscriptions manifests the celebration of a moral commitment, grounded on a bodily condition as a subterfuge for construction and recognition of subjectivities

Neurons Controlling Aplysia Feeding Inhibit Themselves by Continuous NO Production

Neural activity can be affected by nitric oxide (NO) produced by spiking neurons. Can neural activity also be affected by NO produced in neurons in the absence of spiking?Applying an NO scavenger to quiescent Aplysia buccal ganglia initiated fictive feeding, indicating that NO production at rest inhibits feeding. The inhibition is in part via effects on neurons B31/B32, neurons initiating food consumption. Applying NO scavengers or nitric oxide synthase (NOS) blockers to B31/B32 neurons cultured in isolation caused inactive neurons to depolarize and fire, indicating that B31/B32 produce NO tonically without action potentials, and tonic NO production contributes to the B31/B32 resting potentials. Guanylyl cyclase blockers also caused depolarization and firing, indicating that the cGMP second messenger cascade, presumably activated by the tonic presence of NO, contributes to the B31/B32 resting potential. Blocking NO while voltage-clamping revealed an inward leak current, indicating that NO prevents this current from depolarizing the neuron. Blocking nitrergic transmission had no effect on a number of other cultured, isolated neurons. However, treatment with NO blockers did excite cerebral ganglion neuron C-PR, a command-like neuron initiating food-finding behavior, both in situ, and when the neuron was cultured in isolation, indicating that this neuron also inhibits itself by producing NO at rest.Self-inhibitory, tonic NO production is a novel mechanism for the modulation of neural activity. Localization of this mechanism to critical neurons in different ganglia controlling different aspects of a behavior provides a mechanism by which a humeral signal affecting background NO production, such as the NO precursor L-arginine, could control multiple aspects of the behavior

Born to learn: The inspiration, progress, and future of evolved plastic artificial neural networks

Biological plastic neural networks are systems of extraordinary computational capabilities shaped by evolution, development, and lifetime learning. The interplay of these elements leads to the emergence of adaptive behavior and intelligence. Inspired by such intricate natural phenomena, Evolved Plastic Artificial Neural Networks (EPANNs) use simulated evolution in-silico to breed plastic neural networks with a large variety of dynamics, architectures, and plasticity rules: these artificial systems are composed of inputs, outputs, and plastic components that change in response to experiences in an environment. These systems may autonomously discover novel adaptive algorithms, and lead to hypotheses on the emergence of biological adaptation. EPANNs have seen considerable progress over the last two decades. Current scientific and technological advances in artificial neural networks are now setting the conditions for radically new approaches and results. In particular, the limitations of hand-designed networks could be overcome by more flexible and innovative solutions. This paper brings together a variety of inspiring ideas that define the field of EPANNs. The main methods and results are reviewed. Finally, new opportunities and developments are presented

Distributed network organization underlying feeding behavior in the mollusk Lymnaea

The aim of the work reviewed here is to relate the properties of individual neurons to network organization and behavior using the feeding system of the gastropod mollusk, Lymnaea. Food ingestion in this animal involves sequences of rhythmic biting movements that are initiated by the application of a chemical food stimulus to the lips and esophagus. We investigated how individual neurons contribute to various network functions that are required for the generation of feeding behavior such as rhythm generation, initiation ('decision making'), modulation and hunger and satiety. The data support the view that feeding behavior is generated by a distributed type of network organization with individual neurons often contributing to more than one network function, sharing roles with other neurons. Multitasking in a distributed type of network would be 'economically' sensible in the Lymnaea feeding system where only about 100 neurons are available to carry out a variety of complex tasks performed by millions of neurons in the vertebrate nervous system. Having complementary and potentially alternative mechanisms for network functions would also add robustness to what is a 'noisy' network where variable firing rates and synaptic strengths are commonly encountered in electrophysiological recording experiments

Explicit Logic Circuits Discriminate Neural States

The magnitude and apparent complexity of the brain's connectivity have left explicit networks largely unexplored. As a result, the relationship between the organization of synaptic connections and how the brain processes information is poorly understood. A recently proposed retinal network that produces neural correlates of color vision is refined and extended here to a family of general logic circuits. For any combination of high and low activity in any set of neurons, one of the logic circuits can receive input from the neurons and activate a single output neuron whenever the input neurons have the given activity state. The strength of the output neuron's response is a measure of the difference between the smallest of the high inputs and the largest of the low inputs. The networks generate correlates of known psychophysical phenomena. These results follow directly from the most cost-effective architectures for specific logic circuits and the minimal cellular capabilities of excitation and inhibition. The networks function dynamically, making their operation consistent with the speed of most brain functions. The networks show that well-known psychophysical phenomena do not require extraordinarily complex brain structures, and that a single network architecture can produce apparently disparate phenomena in different sensory systems

Multipolar Reactive DPD: A Novel Tool for Spatially Resolved Systems Biology

This article reports about a novel extension of dissipative particle dynamics (DPD) that allows the study of the collective dynamics of complex chemical and structural systems in a spatially resolved manner with a combinatorially complex variety of different system constituents. We show that introducing multipolar interactions between particles leads to extended membrane structures emerging in a self-organized manner and exhibiting both the necessary mechanical stability for transport and fluidity so as to provide a two-dimensional self-organizing dynamic reaction environment for kinetic studies in the context of cell biology. We further show that the emergent dynamics of extended membrane bound objects is in accordance with scaling laws imposed by physics.Comment: submitted to CMSB 0

The development of eye movements in the zebrafish ( Danio rerio )

We investigated the development of oculomotor activity in zebrafish embryos and larvae of ages 48-96 hrs postfertilization (hpf). The optokinetic response (OKR: smooth tracking movements evoked by a rotating striped drum) improved steadily after its onset at 73 hpf, and by 96 hpf had a achieved a gain (eye velocity/drum velocity) of 0.9, comparable to adult performance. Reset movements (the fast phase of optokinetic nystagmus) developed over 75–81 hpf. The vestibuloocular reflex (VOR: compensatory eye movements evoked by passive rotation of the head) developed over 74–81 hpf, and the associated reset movements, over 76–81 hpf. The VOR was qualitatively normal in dark-reared fish, which excludes an essential role for visual experience in its early development. Spontaneous saccadic movements (the fast shift of eye position) appeared between 81 and 96 hpf, and at 96 hpf had maximum velocities that were comparable to adults. These results are compared to, and found to be incompatible with, two earlier ideas of motor development: behavioral “differentiation” and “encephalization.” © 1997 John Wiley & Sons, Inc. Dev Psychobiol 31: 267–276, 1997Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34395/1/4_ftp.pd