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Article: Complexity of the Nano-Bio Interface and the Tortuous Path of Metal Oxides in Biological Systems.

Erlichman, Joseph S / Leiter, James C

2021 Volume 10, Issue 4

Abstract: Metal oxide nanoparticles (NPs) have received a great deal of attention as potential theranostic agents. Despite extensive work on a wide variety of metal oxide NPs, few chemically active metal oxide NPs have received Food and Drug Administration (FDA) ... ...

Abstract	Metal oxide nanoparticles (NPs) have received a great deal of attention as potential theranostic agents. Despite extensive work on a wide variety of metal oxide NPs, few chemically active metal oxide NPs have received Food and Drug Administration (FDA) clearance. The clinical translation of metal oxide NP activity, which often looks so promising in preclinical studies, has not progressed as rapidly as one might expect. The lack of FDA approval for metal oxide NPs appears to be a consequence of the complex transformation of NP chemistry as any given NP passes through multiple extra- and intracellular environments and interacts with a variety of proteins and transport processes that may degrade or transform the chemical properties of the metal oxide NP. Moreover, the translational models frequently used to study these materials do not represent the final therapeutic environment well, and studies in reduced preparations have, all too frequently, predicted fundamentally different physico-chemical properties from the biological activity observed in intact organisms. Understanding the evolving pharmacology of metal oxide NPs as they interact with biological systems is critical to establish translational test systems that effectively predict future theranostic activity.
Language	English
Publishing date	2021-04-01
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox10040547
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Article: Complexity of the Nano-Bio Interface and the Tortuous Path of Metal Oxides in Biological Systems

Erlichman, Joseph S / Leiter, James C

Antioxidants. 2021 Apr. 01, v. 10, no. 4

2021

Abstract	Metal oxide nanoparticles (NPs) have received a great deal of attention as potential theranostic agents. Despite extensive work on a wide variety of metal oxide NPs, few chemically active metal oxide NPs have received Food and Drug Administration (FDA) clearance. The clinical translation of metal oxide NP activity, which often looks so promising in preclinical studies, has not progressed as rapidly as one might expect. The lack of FDA approval for metal oxide NPs appears to be a consequence of the complex transformation of NP chemistry as any given NP passes through multiple extra- and intracellular environments and interacts with a variety of proteins and transport processes that may degrade or transform the chemical properties of the metal oxide NP. Moreover, the translational models frequently used to study these materials do not represent the final therapeutic environment well, and studies in reduced preparations have, all too frequently, predicted fundamentally different physico-chemical properties from the biological activity observed in intact organisms. Understanding the evolving pharmacology of metal oxide NPs as they interact with biological systems is critical to establish translational test systems that effectively predict future theranostic activity.
Keywords	Food and Drug Administration ; bioactive properties ; pharmacology ; therapeutics
Language	English
Dates of publication	2021-0401
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox10040547
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Article: Variable

Heckman, Karin L / Estevez, Ana Y / DeCoteau, William / Vangellow, Stephanie / Ribeiro, Samantha / Chiarenzelli, Joseph / Hays-Erlichman, Bonnie / Erlichman, Joseph S

Frontiers in pharmacology

2020 Volume 10, Page(s) 1599

Abstract: Cerium oxide nanoparticles (CeNPs) exhibit redox ... ...

Abstract	Cerium oxide nanoparticles (CeNPs) exhibit redox capacity
Language	English
Publishing date	2020-01-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2019.01599
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Article ; Online: Complexity of the Nano-Bio Interface and the Tortuous Path of Metal Oxides in Biological Systems

Joseph S. Erlichman / J. C. Leiter

Antioxidants, Vol 10, Iss 547, p

2021 Volume 547

Abstract	Metal oxide nanoparticles (NPs) have received a great deal of attention as potential theranostic agents. Despite extensive work on a wide variety of metal oxide NPs, few chemically active metal oxide NPs have received Food and Drug Administration (FDA) clearance. The clinical translation of metal oxide NP activity, which often looks so promising in preclinical studies, has not progressed as rapidly as one might expect. The lack of FDA approval for metal oxide NPs appears to be a consequence of the complex transformation of NP chemistry as any given NP passes through multiple extra- and intracellular environments and interacts with a variety of proteins and transport processes that may degrade or transform the chemical properties of the metal oxide NP. Moreover, the translational models frequently used to study these materials do not represent the final therapeutic environment well, and studies in reduced preparations have, all too frequently, predicted fundamentally different physico-chemical properties from the biological activity observed in intact organisms. Understanding the evolving pharmacology of metal oxide NPs as they interact with biological systems is critical to establish translational test systems that effectively predict future theranostic activity.
Keywords	cell trafficking ; endocytosis ; exocytosis ; protein corona ; redox chemistry ; Therapeutics. Pharmacology ; RM1-950
Subject code	540
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The potential of cerium oxide nanoparticles (nanoceria) for neurodegenerative disease therapy.

Estevez, Ana Y / Erlichman, Joseph S

Nanomedicine (London, England)

2014 Volume 9, Issue 10, Page(s) 1437–1440

MeSH term(s)	Animals ; Antioxidants/administration & dosage ; Brain/drug effects ; Brain/metabolism ; Cerium/administration & dosage ; Feasibility Studies ; Humans ; Metal Nanoparticles/administration & dosage ; Models, Neurological ; Neurodegenerative Diseases/drug therapy ; Neurodegenerative Diseases/metabolism ; Reactive Oxygen Species/metabolism
Chemical Substances	Antioxidants ; Reactive Oxygen Species ; Cerium (30K4522N6T) ; ceric oxide (619G5K328Y)
Language	English
Publishing date	2014-07
Publishing country	England
Document type	Editorial
ZDB-ID	2277839-1
ISSN	1748-6963 ; 1743-5889
ISSN (online)	1748-6963
ISSN	1743-5889
DOI	10.2217/nnm.14.87
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Article ; Online: Glia modulation of the extracellular milieu as a factor in central CO2 chemosensitivity and respiratory control.

Erlichman, Joseph S / Leiter, J C

Journal of applied physiology (Bethesda, Md. : 1985)

2010 Volume 108, Issue 6, Page(s) 1803–1811

Abstract: We discuss the influence of astrocytes on respiratory function, particularly central CO2 chemosensitivity. Fluorocitrate (FC) poisons astrocytes, and studies in intact animals using FC provide strong evidence that disrupting astrocytic function can ... ...

Abstract	We discuss the influence of astrocytes on respiratory function, particularly central CO2 chemosensitivity. Fluorocitrate (FC) poisons astrocytes, and studies in intact animals using FC provide strong evidence that disrupting astrocytic function can influence CO2 chemosensitivity and ventilation. Gap junctions interconnect astrocytes and contribute to K+ homeostasis in the extracellular fluid (ECF). Blocking gap junctions alters respiratory control, but proof that this is truly an astrocytic effect is lacking. Intracellular pH regulation of astrocytes has reciprocal effects on extracellular pH. Electrogenic sodium-bicarbonate transport (NBCe) is present in astrocytes. The activity of NBCe alkalinizes intracellular pH and acidifies extracellular pH when activated by depolarization (and a subset of astrocytes are depolarized by hypercapnia). Thus, to the extent that astrocytic intracellular pH regulation during hypercapnia lowers extracellular pH, astrocytes will amplify the hypercapnic stimulus and may influence central chemosensitivity. However, the data so far provide only inferential support for this hypothesis. A lactate shuttle from astrocytes to neurons seems to be active in the retrotrapezoid nucleus (RTN) and important in setting the chemosensory stimulus in the RTN (and possibly other chemosensory nuclei). Thus astrocytic processes, so vital in controlling the constituents of the ECF in the central nervous system, may profoundly influence central CO2 chemosensitivity and respiratory control.
MeSH term(s)	Animals ; Brain Stem/metabolism ; Carbon Dioxide/metabolism ; Chemoreceptor Cells/metabolism ; Feedback, Physiological/physiology ; Humans ; Neuroglia/metabolism ; Respiratory Mechanics
Chemical Substances	Carbon Dioxide (142M471B3J)
Language	English
Publishing date	2010-01-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	219139-8
ISSN	1522-1601 ; 0021-8987 ; 0161-7567 ; 8750-7587
ISSN (online)	1522-1601
ISSN	0021-8987 ; 0161-7567 ; 8750-7587
DOI	10.1152/japplphysiol.01321.2009
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Article ; Online: Real-time monitoring of superoxide accumulation and antioxidant activity in a brain slice model using an electrochemical cytochrome c biosensor.

Ganesana, Mallikarjunarao / Erlichman, Joseph S / Andreescu, Silvana

Free radical biology & medicine

2012 Volume 53, Issue 12, Page(s) 2240–2249

Abstract: The overproduction of reactive oxygen species and the resulting damage are central to the pathology of many diseases. The study of the temporal and spatial accumulation of reactive oxygen species has been limited because of the lack of specific probes ... ...

Abstract	The overproduction of reactive oxygen species and the resulting damage are central to the pathology of many diseases. The study of the temporal and spatial accumulation of reactive oxygen species has been limited because of the lack of specific probes and techniques capable of continuous measurement. We demonstrate the use of a miniaturized electrochemical cytochrome c (Cyt c) biosensor for real-time measurements and quantitative assessment of superoxide production and inactivation by natural and engineered antioxidants in acutely prepared brain slices from mice. Under control conditions, superoxide radicals produced from the hippocampal region of the brain in 400-μm-thick sections were well within the range of detection of the electrode. Exposure of the slices to ischemic conditions increased the superoxide production twofold and measurements from the slices were stable over a 3- to 4-h period. The stilbene derivative and anion channel inhibitor 4,4'-diisothiocyano-2,2'-disulfonic stilbene markedly reduced the extracellular superoxide signal under control conditions, suggesting that a transmembrane flux of superoxide into the extracellular space may occur as part of normal redox signaling. The specificity of the electrode for superoxide released by cells in the hippocampus was verified by the exogenous addition of superoxide dismutase (SOD), which decreased the superoxide signal in a dose-dependent manner. Similar results were seen with the addition of the SOD mimetic cerium oxide nanoparticles (nanoceria), in that the superoxide anion radical scavenging activity of nanoceria with an average diameter of 15 nm was equivalent to 527 U of SOD for each 1 μg/ml of nanoceria added. This study demonstrates the potential of electrochemical biosensors for studying real-time dynamics of reactive oxygen species in a biological model and the utility of these measurements in defining the relative contribution of superoxide to oxidative injury.
MeSH term(s)	Animals ; Antioxidants/pharmacology ; Biosensing Techniques ; Brain Ischemia/metabolism ; Calibration ; Cattle ; Cell Hypoxia ; Cerium/pharmacology ; Cytochromes c/chemistry ; Electrochemical Techniques ; Electrodes ; Female ; Hippocampus/drug effects ; Hippocampus/metabolism ; Horses ; Hypoxanthine/chemistry ; Immobilized Proteins/chemistry ; In Vitro Techniques ; Male ; Mice ; Nanoparticles ; Superoxide Dismutase/chemistry ; Superoxides/metabolism ; Voltage-Dependent Anion Channels/metabolism ; Xanthine Oxidase/chemistry
Chemical Substances	Antioxidants ; Immobilized Proteins ; Voltage-Dependent Anion Channels ; Superoxides (11062-77-4) ; Hypoxanthine (2TN51YD919) ; Cerium (30K4522N6T) ; ceric oxide (619G5K328Y) ; Cytochromes c (9007-43-6) ; Superoxide Dismutase (EC 1.15.1.1) ; Xanthine Oxidase (EC 1.17.3.2)
Language	English
Publishing date	2012-10-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2012.10.540
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Article ; Online: ATP, glia and central respiratory control.

Erlichman, Joseph S / Leiter, J C / Gourine, Alexander V

Respiratory physiology & neurobiology

2010 Volume 173, Issue 3, Page(s) 305–311

Abstract: ... chemosensory site(s) on the surface of the medulla oblongata. Systemic hypoxia in anesthetized rats was also ...

Abstract	An increase in PCO(2) in the arterial blood triggers immediate release of ATP from the ventral chemosensory site(s) on the surface of the medulla oblongata. Systemic hypoxia in anesthetized rats was also associated with increased ATP release on the ventral medullary surface. During both hypoxia and hypercapnia, ATP and possibly other gliotransmitters released in the ventral medulla seemed to enhance cardiorespiratory responses to these stressors, and some of this ATP was proposed to be derived from astrocytes. Astrocytes also play a vital role controlling local blood flow. Astrocytes are activated by neurotransmitter release - especially glutamate and ATP. The astrocytic activation is manifest as a rise in intracellular Ca(2+) that is closely coupled to the metabolic activity of neurons in the active area. The activation of astrocytes spreads as a wave from astrocyte to astrocyte and causes release of ATP, adenosine, and other gliotransmitters that may alter neuronal function in the region of astrocytic activation. In addition, ATP, adenosine and other vasoactive substances, when released at the endfeet of astrocytes, interact with vascular receptors that may either dilate or constrict the vessels in the region closely adjacent to the site of neuronal activity. Thus, astrocytes seem to integrate neuronal metabolic needs by responding to the level of neuronal activity to regulate local blood flow and cardiorespiratory responses to hypoxia and hypercapnia to match substrate need (oxygen and glucose) with substrate availability and with the removal of CO(2). In so doing, astrocytes assume a larger role in information processing and in the regulation of neuronal activity and homeostasis of the entire organism than has been ascribed to them in the past.
MeSH term(s)	Adenosine Triphosphate/metabolism ; Animals ; Carbon Dioxide/blood ; Cerebrovascular Circulation/physiology ; Chemoreceptor Cells/metabolism ; Humans ; Medulla Oblongata/blood supply ; Medulla Oblongata/cytology ; Medulla Oblongata/physiology ; Neuroglia/metabolism ; Neurons/cytology ; Neurons/metabolism ; Respiratory Physiological Phenomena
Chemical Substances	Carbon Dioxide (142M471B3J) ; Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2010-06-23
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2077867-3
ISSN	1878-1519 ; 1569-9048
ISSN (online)	1878-1519
ISSN	1569-9048
DOI	10.1016/j.resp.2010.06.009
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Article ; Online: Ionic mechanisms of central CO(2) chemosensitivity.

Chernov, Mykyta M / Erlichman, Joseph S / Leiter, J C

Respiratory physiology & neurobiology

2010 Volume 173, Issue 3, Page(s) 298–304

Abstract: A comparative analysis of chemosensory systems in invertebrates and vertebrates reveals that different animals use similar strategies when sensing CO(2) to control respiration. A variety of animals possess neurons that respond to changes in pH. These ... ...

Abstract	A comparative analysis of chemosensory systems in invertebrates and vertebrates reveals that different animals use similar strategies when sensing CO(2) to control respiration. A variety of animals possess neurons that respond to changes in pH. These respiratory chemoreceptor neurons seem to rely largely on pH-dependent inhibition of potassium channels, but the channels do not appear to be uniquely adapted to detect pH. The 'chemosensory' potassium channels identified thus far are widely distributed, common potassium channels. The pH-sensitivity is a common feature of the channels whether the channels are in chemosensory neurons or not. Thus, the pattern of synaptic connectivity and the mix of potassium channels expressed seem to determine whether a neuron is chemosensory or not, rather than any special adaptation of a channel for pH-sensitivity. Moreover, there are often multiple pH-sensitive channels in each chemosensory neuron. These ionic mechanisms may, however, be only part of the chemosensory process, and pH-dependent modulation of synaptic activity seems to contribute to central chemosensitivity as well. In addition, the exploration of the mechanisms of pH-dependent modulation of ion channel activity in chemosensory cells is incomplete: additional mechanisms of pH modulation of channel activity may be found, and addition conductances, other than potassium channels, may participate in the chemosensory process.
MeSH term(s)	Animals ; Brain/cytology ; Brain/physiology ; Carbon Dioxide/metabolism ; Chemoreceptor Cells/cytology ; Chemoreceptor Cells/metabolism ; Humans ; Hydrogen-Ion Concentration ; Ion Channels/metabolism ; Neurons/cytology ; Neurons/metabolism ; Respiratory Physiological Phenomena
Chemical Substances	Ion Channels ; Carbon Dioxide (142M471B3J)
Language	English
Publishing date	2010-04-07
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2077867-3
ISSN	1878-1519 ; 1569-9048
ISSN (online)	1878-1519
ISSN	1569-9048
DOI	10.1016/j.resp.2010.03.022
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Article ; Online: Neuronal variability during handwriting: lognormal distribution.

Rupasov, Valery I / Lebedev, Mikhail A / Erlichman, Joseph S / Linderman, Michael

PloS one

2012 Volume 7, Issue 4, Page(s) e34759

Abstract: We examined time-dependent statistical properties of electromyographic (EMG) signals recorded from intrinsic hand muscles during handwriting. Our analysis showed that trial-to-trial neuronal variability of EMG signals is well described by the lognormal ... ...

Abstract	We examined time-dependent statistical properties of electromyographic (EMG) signals recorded from intrinsic hand muscles during handwriting. Our analysis showed that trial-to-trial neuronal variability of EMG signals is well described by the lognormal distribution clearly distinguished from the Gaussian (normal) distribution. This finding indicates that EMG formation cannot be described by a conventional model where the signal is normally distributed because it is composed by summation of many random sources. We found that the variability of temporal parameters of handwriting--handwriting duration and response time--is also well described by a lognormal distribution. Although, the exact mechanism of lognormal statistics remains an open question, the results obtained should significantly impact experimental research, theoretical modeling and bioengineering applications of motor networks. In particular, our results suggest that accounting for lognormal distribution of EMGs can improve biomimetic systems that strive to reproduce EMG signals in artificial actuators.
MeSH term(s)	Algorithms ; Electromyography/methods ; Handwriting ; Humans ; Models, Statistical
Language	English
Publishing date	2012-04-13
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0034759
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