Nanomaterials are engineered structures with at least one dimension of 100 nanometers or less. These materials are increasingly being used for commercial purposes such as fillers, opacifiers, catalysts, semiconductors, cosmetics, microelectronics, and drug carriers. Materials in this size range may approach the length scale at which some specific physical or chemical interactions with their environment can occur. As a result, their properties differ substantially from those bulk materials of the same composition, allowing them to perform exceptional feats of conductivity, reactivity, and optical sensitivity. Possible undesirable results of these capabilities are harmful interactions with biological systems and the environment, with the potential to generate toxicity. The establishment of principles and test procedures to ensure safe manufacture and use of nanomaterials in the marketplace is urgently required and achievable.

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Toxic Potential of Materials at the Nanolevel

Capsaicin, the main pungent ingredient in 'hot' chilli peppers, elicits a sensation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system We have used an expression cloning strategy based on calcium influx to isolate a functional cDNA encoding a capsaicin receptor from sensory neurons This receptor is a non-selective cation channel that is structurally related to members of the TRP family of ion channels The cloned capsaicin receptor is also activated by increases in temperature in the noxious range, suggesting that it functions as a transducer of painful thermal stimuli in vivo

/pdf/the-capsaicin-receptor-a-heat-activated-ion-channel-in-the-57mhjl9hkd.pdf

The capsaicin receptor: a heat-activated ion channel in the pain pathway

Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death

In multicellular organisms, homeostasis is maintained through a balance between cell proliferation and cell death. Although much is known about the control of cell proliferation, less is known about the control of cell death. Physiologic cell death occurs primarily through an evolutionarily conserved form of cell suicide termed apoptosis. The decision of a cell to undergo apoptosis can be influenced by a wide variety of regulatory stimuli. Recent evidence suggests that alterations in cell survival contribute to the pathogenesis of a number of human diseases, including cancer, viral infections, autoimmune diseases, neurodegenerative disorders, and AIDS (acquired immunodeficiency syndrome). Treatments designed to specifically alter the apoptotic threshold may have the potential to change the natural progression of some of these diseases.

https://science.sciencemag.org/content/sci/267/5203/1456.full.pdf

Apoptosis in the pathogenesis and treatment of disease

Over 60 years ago, Selye1 recognized the paradox that the physiologic systems activated by stress can not only protect and restore but also damage the body. What links these seemingly contradictory roles? How does stress influence the pathogenesis of disease, and what accounts for the variation in vulnerability to stress-related diseases among people with similar life experiences? How can stress-induced damage be quantified? These and many other questions still challenge investigators. This article reviews the long-term effect of the physiologic response to stress, which I refer to as allostatic load.2 Allostasis — the ability to achieve stability through change3 — . . .

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Protective and Damaging Effects of Stress Mediators

Glutamate neurotoxicity and diseases of the nervous system

Excitotoxicity refers to the ability of glutamate or related excitatory amino acids to mediate the death of central neurons under certain conditions, for example, after intense exposure. Such excitotoxic neuronal death may contribute to the pathogenesis of brain or spinal cord injury associated with several human disease states. Excitotoxicity has substantial cellular specificity and, in most cases, is mediated by glutamate receptors. On average, NMDA receptors activation may be able to trigger lethal injury more rapidly than AMPA or kainate receptor activation, perhaps reflecting a greater ability to induce calcium influx and subsequent cellular calcium overload. It is possible that excitotoxic death may share some mechanisms with other forms of neuronal death.

Excitotoxic cell death

Dennis W. ChoiDepartment of Neurology, Stanford University, Stanford,California 94305Steven M. RothmanDepartments of Pediatrics, Neurology, and Anatomy and Neurobiology,Washington University, St. Louis, Missouri 63110The human brain depends on its blood supply for a continuous supply ofoxygen and glucose. Irreversible brain damage occurs if blood flow isreduced below about 10 ml/100 g tissue/min and if blood flow is completelyinterrupted, damage will occur in only a few minutes. Unfortunately, suchreductions (ischemia) are common in disease states: either localized individual vascular territories, as in stroke; or globally, as in cardiac arrest.Cerebral hypoxia can also occur in isolation, for example in respiratoryarrest, carbon monoxide poisoning, or near-drowning; pure glucose depri-vation can occur in insulin overdose or a variety of metabolic disorders.As a group, these disorders are a leading cause of neurological disabilityand death; stroke alone is the third most common cause of death in NorthAmerica.Despite its clinical importance, little is known about the cellular patho-genesis of hypoxic-ischemic brain damage, and at present there is noeffective therapy. A critical question has been why brain, more than mostother tissues, is so vulnerable to hypoxic-ischemic insults. In particular,certain neuronal subpopulations, such as hippocampal field CA1 andneocortical layers 3, 5, and 6, are characteristically destroyed after sub-maximal hypoxic-ischenfic exposure. A possible answer has emerged inthe last few years: At least some of this special vulnerability may beaccounted for by the central neurotoxicity of the endogenous excitatory1710147-006X/90/0301 ~:1171 $02.00www.annualreviews.org/aronline Annual Reviews

The role of glutamate neurotoxicity in hypoxic- ischemic neuronal death

The cellular mechanisms by which excess exposure to the excitatory neurotransmitter glutamate can produce neuronal injury are unknown. More than a decade ago it was hypothesized that glutamate neurotoxicity (GNT) is a direct consequence of excessive neuronal excitation (“excitotoxicity” hypothesis); more recently, it has been hypothesized that a Ca influx triggered by glutamate exposure might mediate GNT (Ca hypothesis). A basic test to discriminate between these hypotheses would be to determine the dependence of GNT on the extracellular ionic environment. The excitotoxicity hypothesis predicts that GNT should depend critically on the presence of extracellular Na, since that ion appears to mediate glutamate neuroexcitation in the CNS; the Ca hypothesis predicts that GNT should depend critically on the presence of extracellular Ca. The focus of the present experiments was to determine the effects of several alterations in the extracellular ionic environment upon the serial morphologic changes that occur after mouse neocortical neurons in cell culture receive toxic exposure to glutamate. The results suggest that GNT in cortical neurons can be separated into 2 components distinguishable on the basis of differences in time course and ionic dependence. The first component, marked by neuronal swelling, occurs early, is dependent on extracellular Na and Cl, can be mimicked by high K, and is thus possibly “excitotoxic.” The second component, marked by gradual neuronal disintegration, occurs late, is dependent on extracellular Ca, can be mimicked by A23187, and is thus possibly mediated by a transmembrane influx of Ca. While either component alone is ultimately capable of producing irreversible neuronal injury, the Ca-dependent mechanism predominates at lower exposures to glutamate. Glutamate exposure likely leads to a Ca influx both through glutamate-activated cation channels and through voltage- dependent Ca channels activated by membrane depolarization. Addition of 20 mM Mg, however, did not substantially block GNT; this finding, together with the observation that GNT is largely preserved in sodium- free solution, supports the notion that the activation of voltage- dependent Ca channels may not be required for lethal Ca entry. The possibility that N-methyl-D-aspartate receptors may play a dominant role in mediating glutamate-induced lethal Ca influx is discussed.

https://www.jneurosci.org/content/jneuro/7/2/369.full.pdf

Dennis W. Choi

Papers

Glutamate neurotoxicity and diseases of the nervous system

Excitotoxic cell death

The role of glutamate neurotoxicity in hypoxic- ischemic neuronal death

Ionic dependence of glutamate neurotoxicity

Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage.