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Article ; Online: An Overview of the Mechanisms of Abnormal GABAergic Interneuronal Cortical Migration Associated with Prenatal Ethanol Exposure.

Shenoda, Botros B

2017 Volume 42, Issue 5, Page(s) 1279–1287

Abstract: GABAergic Interneuronal migration constitutes an essential process during corticogenesis. Derived from progenitor cells located in the proliferative zones of the ventral telencephalon, newly generated GABAergic Interneuron migrate to their cortical ... ...

Abstract	GABAergic Interneuronal migration constitutes an essential process during corticogenesis. Derived from progenitor cells located in the proliferative zones of the ventral telencephalon, newly generated GABAergic Interneuron migrate to their cortical destinations. Cortical dysfunction associated with defects in neuronal migration results in severe developmental consequences. There is growing evidence linking prenatal ethanol exposure to abnormal GABAergic interneuronal migration and subsequent cortical dysfunction. Investigating the pathophysiological mechanisms behind disrupted GABAergic interneuronal migration encountered with prenatal alcohol exposure is crucial for understanding and managing fetal alcohol spectrum disorders. This review explores the molecular pathways regulating GABAergic interneuronal cortical migration that might be altered by prenatal ethanol exposure thus opening new avenues for further research in this topic.
Language	English
Publishing date	2017-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	199335-5
ISSN	1573-6903 ; 0364-3190
ISSN (online)	1573-6903
ISSN	0364-3190
DOI	10.1007/s11064-016-2169-5
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Article ; Online: Syndrome of Inappropriate Antidiuretic Hormone Release During Ketamine Infusion in Complex Regional Syndrome Patient Receiving Intrathecal Baclofen: A Case Report.

Shenoda, Botros B / Krevolin, Larry E / Sherman, Michael

A&A practice

2019 Volume 13, Issue 10, Page(s) 386–388

Abstract: Complex regional pain syndrome (CRPS) is a severely disabling condition that typically develops after an inciting traumatic event. Ketamine infusion in subanesthetic dose provides sustained analgesia in selected cases of CRPS. In general, ketamine ... ...

Abstract	Complex regional pain syndrome (CRPS) is a severely disabling condition that typically develops after an inciting traumatic event. Ketamine infusion in subanesthetic dose provides sustained analgesia in selected cases of CRPS. In general, ketamine treatment does not significantly affect electrolyte or water balance. Here, we report a case of a CRPS patient on intrathecal baclofen pump developing syndrome of inappropriate antidiuretic hormone release (SIADH) during ketamine infusion. Prophylactic treatment with intravenous loop diuretics was successful in preventing the development of SIADH during ketamine infusion during subsequent infusions in this case.
MeSH term(s)	Baclofen/administration & dosage ; Baclofen/adverse effects ; Complex Regional Pain Syndromes/drug therapy ; Female ; Humans ; Inappropriate ADH Syndrome/chemically induced ; Inappropriate ADH Syndrome/drug therapy ; Injections, Intraventricular ; Injections, Spinal ; Ketamine/administration & dosage ; Ketamine/adverse effects ; Middle Aged ; Sodium Potassium Chloride Symporter Inhibitors/administration & dosage ; Sodium Potassium Chloride Symporter Inhibitors/therapeutic use ; Treatment Outcome
Chemical Substances	Sodium Potassium Chloride Symporter Inhibitors ; Ketamine (690G0D6V8H) ; Baclofen (H789N3FKE8)
Language	English
Publishing date	2019-10-12
Publishing country	United States
Document type	Case Reports ; Journal Article
ISSN	2575-3126
ISSN (online)	2575-3126
DOI	10.1213/XAA.0000000000001091
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Article ; Online: The role of Na+/Ca2+ exchanger subtypes in neuronal ischemic injury.

Shenoda, Botros

Translational stroke research

2015 Volume 6, Issue 3, Page(s) 181–190

Abstract: The Na(+)/Ca(2+) exchanger (NCX) plays an important role in the maintenance of Na(+) and Ca(2+) homeostasis in most cells including neurons under physiological and pathological conditions. It exists in three subtypes (NCX1-3) with different tissue ... ...

Abstract	The Na(+)/Ca(2+) exchanger (NCX) plays an important role in the maintenance of Na(+) and Ca(2+) homeostasis in most cells including neurons under physiological and pathological conditions. It exists in three subtypes (NCX1-3) with different tissue distributions but all of them are present in the brain. NCX transports Na(+) and Ca(2+) in either Ca(2+)-efflux (forward) or Ca(2+)-influx (reverse) mode, depending on membrane potential and transmembrane ion gradients. During neuronal ischemia, Na(+) and Ca(2+) ionic disturbances favor NCX to work in reverse mode, giving rise to increased intracellular Ca(2+) levels, while it may regain its forward mode activity on reperfusion. The exact significance of NCX in neuronal ischemic and reperfusion states remains unclear. The differential role of NCX subtypes in ischemic neuronal injury has been extensively investigated using various pharmacological tools as well as genetic models. This review discusses the mode of action of NCX in ischemic and reperfusion states, the differential roles played by NCX subtypes in these states as well as the role of NCX in pre- and postconditioning. NCX subtypes carry variable roles in ischemic injury. Furthermore, the mode of action of each subtype varies in ischemia and reperfusion states. Thus, therapeutic targeting of NCX in stroke should be based on appropriate timing of the administration of NCX subtype-specific strategies.
MeSH term(s)	Animals ; Brain Ischemia/metabolism ; Humans ; Protein Isoforms/metabolism ; Reperfusion Injury/metabolism ; Sodium-Calcium Exchanger/metabolism
Chemical Substances	Protein Isoforms ; Sodium-Calcium Exchanger
Language	English
Publishing date	2015-06
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2541897-X
ISSN	1868-601X ; 1868-4483
ISSN (online)	1868-601X
ISSN	1868-4483
DOI	10.1007/s12975-015-0395-9
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Article: Modulation of Immune Responses by Exosomes Derived from Antigen-Presenting Cells.

Shenoda, Botros B / Ajit, Seena K

Clinical medicine insights. Pathology

2016 Volume 9, Issue Suppl 1, Page(s) 1–8

Abstract: ... to modulate antigen-specific T cell responses. Exosomes from Dendritic Cells (DCs) can activate T and B cells and have ...

Abstract	Exosome-mediated signaling is important in mediating the inflammatory response. To exert their biological or pathophysiological functions in the recipient cells, exosomes deliver a diverse array of biomacromolecules including long and short coding and non-coding RNAs, proteins, and lipids. Exosomes secreted by antigen-presenting cells can confer therapeutic benefits by attenuating or stimulating the immune response. Exosomes play a crucial role in carrying and presenting functional major histocompatibility peptide complexes to modulate antigen-specific T cell responses. Exosomes from Dendritic Cells (DCs) can activate T and B cells and have been explored for their immunostimulatory properties in cancer therapy. The immunosuppressive properties of exosomes derived from macrophages and DCs can reduce inflammation in animal models for several inflammatory disorders. This review focuses on the protective role of exosomes in attenuating inflammation or augmenting immune response, emphasizing studies on exosomes derived from DCs and macrophages.
Language	English
Publishing date	2016-09-14
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2578761-5
ISSN	1179-5557
ISSN	1179-5557
DOI	10.4137/CPath.S39925
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Article ; Online: Vascular syndromes in liver cirrhosis.

Shenoda, Botros / Boselli, Joseph

Clinical journal of gastroenterology

2019 Volume 12, Issue 5, Page(s) 387–397

Abstract: Liver cirrhosis is associated with multiple vascular syndromes affecting almost all body systems. Many of these syndromes are directly related to impaired liver function and sometimes reversible after liver transplantation while others arise secondary to ...

Abstract	Liver cirrhosis is associated with multiple vascular syndromes affecting almost all body systems. Many of these syndromes are directly related to impaired liver function and sometimes reversible after liver transplantation while others arise secondary to portal hypertension and ascites. Altered expression of angiogenic and vasoactive compounds (most importantly nitric oxide), endothelial dysfunction, dysregulated neurohormonal control, and systemic inflammatory state play differential roles in mediating homeostatic instability and abnormal vasogenic response. Important vascular features encountered in liver disease include portal hypertension, splanchnic overflow, abnormal angiogenesis and shunts, portopulmonary syndrome, hepatopulmonary syndrome, and systemic hyperdynamic circulation. Redistribution of effective circulatory volume deviating from vital organs and pooling in splanchnic circulation is also encountered in liver patients which may lead to devastating outcomes as hepatorenal syndrome. Etiologically, vascular syndromes are not isolated phenomena and vascular dysfunction in one system may lead to the development of another in a different system. This review focuses on understanding the pathophysiological factors underlying vascular syndromes related to chronic liver disease and the potential links among them. Many of these syndromes are associated with high mortality, thus it is crucial to look for early biomarkers for these syndromes and develop novel preventive and therapeutic strategies.
MeSH term(s)	Collateral Circulation/physiology ; Hepatopulmonary Syndrome/etiology ; Hepatopulmonary Syndrome/physiopathology ; Hepatorenal Syndrome/etiology ; Hepatorenal Syndrome/physiopathology ; Humans ; Hypertension, Portal/etiology ; Hypertension, Pulmonary/etiology ; Hypertension, Pulmonary/physiopathology ; Liver Circulation/physiology ; Liver Cirrhosis/complications ; Liver Cirrhosis/physiopathology ; Pulmonary Circulation/physiology ; Splanchnic Circulation/physiology ; Syndrome ; Vascular Diseases/etiology ; Vascular Diseases/physiopathology ; Vasodilation/physiology
Language	English
Publishing date	2019-04-12
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	2429411-1
ISSN	1865-7265 ; 1865-7257
ISSN (online)	1865-7265
ISSN	1865-7257
DOI	10.1007/s12328-019-00956-0
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Article ; Online: Overview of microRNA Modulation in Analgesic Research.

Ramanathan, Sujay / Shenoda, Botros B / Ajit, Seena K

Current protocols in pharmacology

2017 Volume 79, Page(s) 9.25.1–9.25.10

Abstract: MicroRNA(miRNA)-mediated gene regulation underlies cellular processes, playing an important role in homeostasis and diseases. The expression and function of miRNAs are altered by various pharmacological agents, with differences in the endogenous levels ... ...

Abstract	MicroRNA(miRNA)-mediated gene regulation underlies cellular processes, playing an important role in homeostasis and diseases. The expression and function of miRNAs are altered by various pharmacological agents, with differences in the endogenous levels of miRNAs influencing drug efficacy and toxicity. Thus, miRNA levels could be a biomarker for predicting treatment response, efficacy, and safety. In addition, elucidating the mechanistic significance of miRNA alterations can aid in the identification of therapeutic targets and patient selection, and guide personalized therapy. Discussed in this overview are the properties of miRNA, their modulation, and the ways to measure them. The effects of different classes of analgesics, including opioid and non-opioid, are described as examples of drug-induced modifications of miRNA, with a discussion on how measurement of miRNA levels in patients receiving analgesic therapy can assist in maximizing effectiveness while minimizing the untoward responses to this drug class. © 2017 by John Wiley & Sons, Inc.
MeSH term(s)	Analgesics/pharmacology ; Analgesics/therapeutic use ; Animals ; Humans ; MicroRNAs/metabolism ; Pain/drug therapy ; Pain/genetics ; Pain/metabolism
Chemical Substances	Analgesics ; MicroRNAs
Language	English
Publishing date	2017-12-20
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1934-8290
ISSN (online)	1934-8290
DOI	10.1002/cpph.29
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Article ; Online: In Vitro Validation of miRNA-Mediated Gene Expression Linked to Drug Metabolism.

Shenoda, Botros B / Ramanathan, Sujay / Ajit, Seena K

Current protocols in pharmacology

2017 Volume 79, Page(s) 9.26.1–9.26.15

Abstract: Pharmacogenomic approaches used to investigate how genes affect drug responses are critical for designing personalized therapies aimed at maximizing efficacy and minimizing adverse effects. Drug efficacy is often dependent on the sequence and expression ... ...

Abstract	Pharmacogenomic approaches used to investigate how genes affect drug responses are critical for designing personalized therapies aimed at maximizing efficacy and minimizing adverse effects. Drug efficacy is often dependent on the sequence and expression levels of drug target genes or those involved in the metabolism and transport of the therapeutic agent. Expression of these genes, in turn, is negatively regulated by small noncoding miRNAs. The levels of miRNAs in bodily fluids have been studied extensively as potential diagnostic and prognostic biomarkers. Studies have shown that miRNAs regulate multiple genes and sequence homology is used to predict which genes are subject to regulation by a particular miRNA. Once a gene is identified as a potential target for an miRNA of interest, experiments are undertaken to confirm that the miRNA interacts with the target gene and can alter its level of expression and/or its activity. For example, the differential expression of miRNAs in whole blood obtained from good and poor responders to ketamine has been reported both prior to, and following treatment for complex regional pain syndrome. In this case, hsa-miR-548d-5p was significantly lower in poor responders relative to good responders. This miRNA was predicted to target UDP-glucuronyl transferase 1A1 (UGT1A1), a key drug metabolizing enzyme. Described in this unit are protocols used to confirm miR-548d-5p-mediated UGT1A1 regulation. The approaches described can be employed broadly for the validation of miRNA-mediated negative regulation of any gene. Determining miRNA-mediated regulation of enzymes and transporters affecting drug metabolism is a critical step in designing personalized therapy and for understanding the mechanisms responsible for variations in the responses to therapeutic agents. © 2017 by John Wiley & Sons, Inc.
MeSH term(s)	Gene Expression Regulation ; Glucuronosyltransferase/genetics ; Glucuronosyltransferase/metabolism ; HEK293 Cells ; Hep G2 Cells ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Pharmaceutical Preparations/metabolism ; RNA, Messenger/genetics
Chemical Substances	MicroRNAs ; Pharmaceutical Preparations ; RNA, Messenger ; UGT1A1 enzyme (EC 2.4.1.-) ; Glucuronosyltransferase (EC 2.4.1.17)
Language	English
Publishing date	2017-12-20
Publishing country	United States
Document type	Journal Article
ISSN	1934-8290
ISSN (online)	1934-8290
DOI	10.1002/cpph.30
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Article ; Online: Hsa-miR-34a mediated repression of corticotrophin releasing hormone receptor 1 regulates pro-opiomelanocortin expression in patients with complex regional pain syndrome.

Shenoda, Botros B / Alexander, Guillermo M / Ajit, Seena K

Journal of translational medicine

2016 Volume 14, Page(s) 64

Abstract: Background: Ketamine provides relief for a subset of patients with complex regional pain syndrome (CRPS). The poor responders had a lower body mass index (BMI) relative to responders. Regulation of proopiomelanocortin (POMC) expression is crucial in ... ...

Abstract	Background: Ketamine provides relief for a subset of patients with complex regional pain syndrome (CRPS). The poor responders had a lower body mass index (BMI) relative to responders. Regulation of proopiomelanocortin (POMC) expression is crucial in normal body weight homeostasis. The main objectives of this study were to investigate the mechanisms underlying lower BMI characterizing CRPS patients responding poorly to intravenous ketamine therapy and identify potential biomarkers for predicting response. Methods: We investigated POMC transcript levels in blood from CRPS patients grouped as responders and poor responders to ketamine therapy. Plasma levels of β-endorphin, ACTH and α-MSH were measured by ELISA. We previously identified differential expression of small noncoding microRNA hsa-miR-34a in blood between responders and poor responders. We investigated whether a 11-fold downregulation of hsa-miR-34a in poor responders relative to responders is contributing to the differences in POMC levels by targeting POMC regulator CRHR1. Binding of miR-34a to CRHR1 was assessed using reporter assay; changes in mRNA and protein levels of CRHR1 were used to determine the regulation of CRHR1 by miR-34a. RNA from blood of CRPS and control subjects were used for quantitative PCR for CRHR1. Results: Though ketamine treatment did not alter POMC expression, poor responders had higher levels of POMC mRNA than responders, both before and after treatment. Corticotropin-releasing hormone (CRH) is a key regulator of POMC expression and the biological effects are mediated through its receptor corticotrophin releasing hormone receptor 1 (CRHR1). We show that hsa-miR-34a is a negative regulator of CRHR1; overexpression of hsa-miR-34a in Jurkat cells resulted in reduction of CRH-mediated POMC expression. Poor responders had higher expression of CRHR1 transcripts than responders, indicating a regulatory role for miR-34a. In addition, we found positive correlations between the pretreatment levels of miR-34a to BMI and response to ketamine therapy. Conclusions: Our findings indicate a mechanism by which hsa-miR-34a can regulate the CRH/CRHR1/POMC axis and may influence BMI. Studies in larger patient cohorts are required to confirm the biomarker utility of circulating hsa-miR-34a levels in predicting treatment response to ketamine therapy.
MeSH term(s)	Adrenocorticotropic Hormone/blood ; Body Mass Index ; Complex Regional Pain Syndromes/blood ; Complex Regional Pain Syndromes/drug therapy ; Complex Regional Pain Syndromes/genetics ; Gene Expression Regulation ; HEK293 Cells ; Humans ; Jurkat Cells ; Ketamine/therapeutic use ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Pro-Opiomelanocortin/blood ; Pro-Opiomelanocortin/metabolism ; Receptors, Corticotropin-Releasing Hormone/genetics ; Receptors, Corticotropin-Releasing Hormone/metabolism ; Reproducibility of Results ; alpha-MSH/blood ; beta-Endorphin/blood
Chemical Substances	CRF receptor type 1 ; MIRN34 microRNA, human ; MicroRNAs ; Receptors, Corticotropin-Releasing Hormone ; alpha-MSH (581-05-5) ; beta-Endorphin (60617-12-1) ; Pro-Opiomelanocortin (66796-54-1) ; Ketamine (690G0D6V8H) ; Adrenocorticotropic Hormone (9002-60-2)
Language	English
Publishing date	2016-03-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1479-5876
ISSN (online)	1479-5876
DOI	10.1186/s12967-016-0820-1
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Article ; Online: Presbyesophagus presented with chronic intermittent dysphagia.

Shenoda, Botros / Degen, Kathleen C / Ford, William

Aging clinical and experimental research

2019 Volume 31, Issue 9, Page(s) 1343–1346

Language	English
Publishing date	2019-01-10
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2104785-6
ISSN	1720-8319 ; 1594-0667
ISSN (online)	1720-8319
ISSN	1594-0667
DOI	10.1007/s40520-018-1080-0
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Article ; Online: Late presentation of Takayasu arteritis in geriatric patients.

Shenoda, Botros / Sacher, Daniel C / Adamov, Elena

Aging clinical and experimental research

2019 Volume 32, Issue 2, Page(s) 353–356

Language	English
Publishing date	2019-04-16
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2104785-6
ISSN	1720-8319 ; 1594-0667
ISSN (online)	1720-8319
ISSN	1594-0667
DOI	10.1007/s40520-019-01201-x
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