27 results on '"Amit Ayer"'
Search Results
2. RETRACTED: Differential impact of diabetes and hypertension in the brain: Adverse effects in white matter
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Christina Yang, Adriena DeVisser, Jose A. Martinez, Ilia Poliakov, Alma Rosales-Hernandez, Amit Ayer, Alexandra Garven, Shaila Zaver, Natalia Rincon, Kevin Xu, Ursula I. Tuor, Ann Marie Schmidt, and Cory Toth
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the Authors.It has come to the attention of the corresponding author that portions of the data presented in these manuscripts were not performed properly and represent manipulation. The immunohistochemistry in Figure 6 has been manipulated and the Western blots in Figure 7 were also manipulated. The authors take responsibility for them and apologize to the readership of Neurobiology of Disease.
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- 2011
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3. Retraction notice to 'Differential impact of diabetes and hypertension in the brain: Adverse effects in white matter' [Neurobiol. Dis., 42 (2011) 446–458, http://dx.doi.org/10.1016/j.nbd.2011.02.007]
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Christina Yang, Adriena DeVisser, Jose A. Martinez, Ilia Poliakov, Alma Rosales-Hernandez, Amit Ayer, Alexandra Garven, Shaila Zaver, Natalia Rincon, Kevin Xu, Ursula I. Tuor, Ann Marie Schmidt, and Cory Toth
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Published
- 2014
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4. Retraction notice to 'Differential impact of diabetes and hypertension in the brain: Adverse effects in grey matter' [Neurobiol. Dis., 44 (2011) 161–173, http://dx.doi.org/10.1016/j.nbd.2011.06.005]
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Adriena DeVisser, Christina Yang, Amanda Herring, Jose A. Martinez, Alma Rosales-Hernandez, Ilia Poliakov, Amit Ayer, Alexandra Garven, Shaila Zaver, Natalia Rincon, Kevin Xu, Ursula I. Tuor, Ann Marie Schmidt, and Cory Toth
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Published
- 2014
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5. Analysis of risk factors and clinical sequelae of direct electrical cortical stimulation–induced seizures and afterdischarges in patients undergoing awake mapping
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Amit Ayer, Jessica W. Templer, Zachary A. Abecassis, Matthew C. Tate, Nikhil K. Murthy, and Ketan Yerneni
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Adult ,Male ,Language function ,Stimulation ,Brain mapping ,03 medical and health sciences ,Epilepsy ,0302 clinical medicine ,Risk Factors ,Seizures ,Monitoring, Intraoperative ,Chart review ,Biomarkers, Tumor ,medicine ,Humans ,In patient ,Wakefulness ,Intraoperative Complications ,Promoter Regions, Genetic ,DNA Modification Methylases ,Electrocorticography ,Retrospective Studies ,Brain Mapping ,medicine.diagnostic_test ,Brain Neoplasms ,business.industry ,Tumor Suppressor Proteins ,General Medicine ,Perioperative ,DNA Methylation ,Length of Stay ,Middle Aged ,medicine.disease ,Isocitrate Dehydrogenase ,Tumor Burden ,DNA Repair Enzymes ,030220 oncology & carcinogenesis ,Anesthesia ,Female ,business ,Craniotomy ,030217 neurology & neurosurgery - Abstract
OBJECTIVE Intraoperative stimulation has emerged as a crucial adjunct in neurosurgical oncology, aiding maximal tumor resection while preserving sensorimotor and language function. Despite increasing use in clinical practice of this stimulation, there are limited data on both intraoperative seizure (IS) frequency and the presence of afterdischarges (ADs) in patients undergoing such procedures. The objective of this study was to determine risk factors for IS or ADs, and to determine the clinical consequences of these intraoperative events. METHODS A retrospective chart review was performed for patients undergoing awake craniotomy (both first time and repeat) at a single institution from 2013 to 2018. Hypothesized risk factors for ADs/ISs in patients were evaluated for their effect on ADs and ISs, including tumor location, tumor grade (I–IV), genetic markers (isocitrate dehydrogenase 1/2, O 6-methylguanine-DNA methyltransferase [MGMT] promoter methylation, chromosome 1p/19q codeletion), tumor volume, preoperative seizure status (yes/no), and dosage of preoperative antiepileptic drugs for each patient. Clinical outcomes assessed in patients with IS or ADs were duration of surgery, length of stay, presence of perioperative deficits, and postoperative seizures. Chi-square analysis was performed for binary categorical variables, and a Student t-test was used to assess continuous variables. RESULTS A total of 229 consecutive patients were included in the analysis. Thirty-five patients (15%) experienced ISs. Thirteen (37%) of these 35 patients had experienced seizures that were appreciated clinically and noted on electrocorticography simultaneously, while 8 patients (23%) experienced ISs that were electrographic alone (no obvious clinical change). MGMT promoter methylation was associated with an increased prevalence of ISs (OR 3.3, 95% CI 1.2–7.8, p = 0.02). Forty patients (18%) experienced ADs. Twenty-three percent of patients (9/40) with ISs had ADs prior to their seizure, although ISs and ADs were not statistically associated (p = 0.16). The presence of ADs appeared to be correlated with a shorter length of stay (5.1 ± 2.6 vs 6.1 ± 3.7 days, p = 0.037). Of the clinical features assessed, none were found to be predictive of ADs. Neither IS nor AD, or the presence of either IS or AD (65/229 patients), was a predictor for increased length of stay, presence of perioperative deficits, or postoperative seizures. CONCLUSIONS ISs and ADs, while commonly observed during intraoperative stimulation for brain mapping, do not negatively affect patient outcomes.
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- 2021
6. Impact of medical student involvement on outcomes following spine surgery: A single center analysis of 6485 patients
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Zachary A. Abecassis, Phyo H. Win, Benjamin S. Hopkins, Nader S. Dahdaleh, Constantine L. Karras, Ketan Yerneni, Hyman G. Frankel, and Amit Ayer
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Adult ,Male ,medicine.medical_specialty ,Students, Medical ,Lumbar discectomy ,Operative Time ,Single Center ,Anterior cervical discectomy ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Spine surgery ,Lumbar ,Physiology (medical) ,Humans ,Medicine ,Retrospective Studies ,Posterior fusion ,Education, Medical ,business.industry ,Retrospective cohort study ,General Medicine ,Middle Aged ,Spinal Fusion ,Treatment Outcome ,Neurology ,030220 oncology & carcinogenesis ,Cervical Vertebrae ,Physical therapy ,Operative time ,Female ,Surgery ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Diskectomy - Abstract
Medical student (MS) observation and assistance in the operating room (OR) is a critical component of medical education. Though participation in the operating room has many benefits to the medical student, the potential cost of these experiences to the patients must be taken into account. Other studies have shown differences in outcomes with resident involvement, but the effect of medical students in the OR has been poorly understood. The objective of this study was to understand how medical students and residents impacted surgical outcomes in posterior spinal fusions, anterior cervical discectomy and fusions (ACDFs), and lumbar discectomies. We conducted a retrospective study of patients undergoing posterior spinal fusions, ACDFs, and lumbar discectomies over 15 years. There were 6485 patients met the inclusion criteria of either undergoing a posterior fusion, ACDF or lumbar discectomy (1250 posterior fusion, 1381 ACDF, 3854 lumbar discectomies). Overall, little difference was observed when a medical student was present for surgical outcomes including length of stay, infection, and readmission. For ACDFs, having a medical student present had a significantly longer procedure durations (OR = 1.612, p = 0.001) than cases without. Besides slightly longer operative time (in posterior fusions), there were no major differences in outcomes when a medical student was present in the OR.
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- 2019
7. A Retrospective Cohort Study of Implantable Pulse Generator Surgical Site Infections After Deep Brain Stimulation Surgery With an Antibacterial Envelope
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Jamasb J. Sayadi, Adrian J. Rodrigues, Neal A. Patel, Amit Ayer, and Jaimie M. Henderson
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Anesthesiology and Pain Medicine ,Neurology ,Neurology (clinical) ,General Medicine - Abstract
Deep brain stimulation (DBS) surgery is an established treatment for many patients with neurologic disease, and a common complication of DBS is surgical site infection (SSI). In 2016, neurosurgeons at our institution began enclosing implantable pulse generators (IPGs) within fully absorbable, antibacterial envelopes in patients who underwent initial DBS implantation. We sought to determine whether the use of antibacterial envelopes reduced IPG-related SSIs.We performed a retrospective chart review of all adult patients who underwent initial DBS implantation at Stanford Hospital between November 14, 2012, and November 9, 2020. Operative details, perioperative antibiotics, comorbidities, and postoperative complications were extracted for all patients. Univariate and multivariate logistic regression were used to identify factors associated with SSIs within three months of surgery, and interrupted time-series analysis was performed to assess whether the departmental adoption of the antibacterial envelope led to a reduction in IPG SSIs.Of 344 patients who underwent initial IPG implantation with the antibacterial envelope, one developed an SSI within three months of surgery (0.3%), compared with six of 204 patients (2.9%) who underwent the same procedure without the antibacterial envelope (odds ratio: 0.10, 95% CI: 0.01-0.80, p = 0.031). Univariate logistic regression revealed that the antibacterial envelope and 2000-mg intravenous cefazolin perioperatively were associated with reduced SSI risk, whereas no other factors reached statistical significance. After adjusting for comorbidities, no association remained statistically significant. Interrupted time-series analysis showed a reduction in SSIs after 2016, but the effect was not significant.The adoption of antibacterial envelopes was found to reduce IPG SSIs at the univariate level, but this association did not remain significant after controlling for confounding variables including perioperative antibiotic administration. Although encouraging, this study does not conclusively establish that the use of antibacterial pouches in patients who underwent initial DBS implantation reduces the incidence of IPG SSIs. Future prospective studies that control for confounding variables are necessary to determine the efficacy of antibacterial envelopes in reducing post-DBS infections at the IPG site before clear recommendations can be made.
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- 2021
8. Volume-Staged versus Dose-Staged Radiosurgery, with or without Embolization, in the Treatment of Large Brain Arteriovenous Malformations
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Collin Larkin, Zachary A Abecassis, Ketan Yerneni, Dominic A Nistal, Constantine L Karras, Amit Ayer, Matthew B Potts, and Babak S Jahromi
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Surgery ,Neurology (clinical) - Published
- 2020
9. Continuous, noninvasive wireless monitoring of flow of cerebrospinal fluid through shunts in patients with hydrocephalus
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Yonggang Huang, Joshua M. Rosenow, Zachary A. Abecassis, Yujun Deng, Kaan Börekçi, Matthew B. Potts, Izabela Stankiewicz, Amit Ayer, Chun Ju Su, Jonathan T. Reeder, John A. Rogers, Aaron Banks, Marcus Mims, Mitchell Mims, Tord D Alden, Kyeongha Kwon, Juliet Freudman, Matthew C. Tate, Hsuan Ming Chen, Diana Ostojich, Hany Arafa, Manish Patel, Kun Hyuck Lee, Siddharth Krishnan, Heling Wang, and Robert Loza
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Medicine (miscellaneous) ,Health Informatics ,02 engineering and technology ,lcsh:Computer applications to medicine. Medical informatics ,Article ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,Health Information Management ,Medicine ,Wireless ,In patient ,Silicone tube ,business.industry ,Shunt malfunction ,Diagnostic markers ,021001 nanoscience & nanotechnology ,medicine.disease ,Sensors and biosensors ,Computer Science Applications ,Hydrocephalus ,Vague symptoms ,lcsh:R858-859.7 ,0210 nano-technology ,business ,030217 neurology & neurosurgery ,Shunt (electrical) ,Biomedical engineering - Abstract
Hydrocephalus is a common disorder caused by the buildup of cerebrospinal fluid (CSF) in the brain. Treatment typically involves the surgical implantation of a pressure-regulated silicone tube assembly, known as a shunt. Unfortunately, shunts have extremely high failure rates and diagnosing shunt malfunction is challenging due to a combination of vague symptoms and a lack of a convenient means to monitor flow. Here, we introduce a wireless, wearable device that enables precise measurements of CSF flow, continuously or intermittently, in hospitals, laboratories or even in home settings. The technology exploits measurements of thermal transport through near-surface layers of skin to assess flow, with a soft, flexible, and skin-conformal device that can be constructed using commercially available components. Systematic benchtop studies and numerical simulations highlight all of the key considerations. Measurements on 7 patients establish high levels of functionality, with data that reveal time dependent changes in flow associated with positional and inertial effects on the body. Taken together, the results suggest a significant advance in monitoring capabilities for patients with shunted hydrocephalus, with potential for practical use across a range of settings and circumstances, and additional utility for research purposes in studies of CSF hydrodynamics.
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- 2020
10. Surgical versus conservative treatment of unilateral subaxial non-subluxed facet fractures: A systematic review and meta-analysis
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Zachary A. Abecassis, Collin J. Larkin, Amit Ayer, H. Greg Frankel, Nader S. Dahdaleh, Constantine L. Karras, Ketan Yerneni, and Dominic A Nistal
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Facet (geometry) ,medicine.medical_specialty ,MEDLINE ,Conservative Treatment ,Zygapophyseal Joint ,03 medical and health sciences ,0302 clinical medicine ,Fracture Fixation ,Intervention (counseling) ,Humans ,Medicine ,Retrospective Studies ,business.industry ,Retrospective cohort study ,General Medicine ,Random effects model ,Surgery ,Conservative treatment ,030220 oncology & carcinogenesis ,Relative risk ,Meta-analysis ,Spinal Fractures ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Background and Objective Unilateral subaxial non-subluxed facet fractures (USNSFF) are a pathology seen in traumatic events such as motor vehicle accidents. Management involves either rigid collar bracing or surgical intervention. There currently is no consensus on the treatment of these injuries; this review aims to examine the extant data for recommendations as to which treatment is more effective. Methods MEDLINE, Scopus, and the Cochrane trial register were all searched on January 16, 2020, comparing outcomes for surgical and conservative therapy for USNSFF. The meta-analysis examined rates of treatment failure (need for subsequent operative management) in conservative versus surgical management. The meta-analysis was performed using a random effects model, with visualization in forest and L'Abbe plots. Results We identified six retrospective studies describing 270 patients, with three studies describing 137 patients used in the meta-analysis. Overall, a surgical success rate of 97.7 % and a non-operative success rate of 79.7 % was observed. A random effects model risk ratio of 1.66 (95 % CI: 0.61–4.52) was obtained, suggesting efficacy of surgical management over conservative management. Conclusion The need for surgical intervention subsequent to initial management in the treatment of USNSFF was found to be lower in surgical treatment in contrast to conservative management. However, the studies that were included in the meta-analysis had patient cohorts with much higher rates of neurological deficit and ligamentous injury on presentation, indicating that these may be prognostic indicators of conservative management failure. Furthermore, those that did fail conservative management did not develop severely debilitating conditions. Accordingly, conservative treatment is generally sufficient as a first step in a majority of cases of USNSFF lacking neurological deficit or ligamentous involvement.
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- 2020
11. Epidermal electronics for noninvasive, wireless, quantitative assessment of ventricular shunt function in patients with hydrocephalus
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Zachary A. Abecassis, Kun Hyuck Lee, Yinji Ma, Siddharth Krishnan, Barry Ng, John A. Rogers, Chen Wei, Yonggang Huang, Camille Goudeseune, Natalie Kim, Philipp Gutruf, Juliet Freudman, Matthew C. Tate, Matthew B. Potts, Izabela Stankiewicz, Jong Yoon Lee, Tyler R. Ray, Nikhil K. Murthy, Amit Ayer, John Ciraldo, Grace Young, Xue Feng, and Julia Stillman
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02 engineering and technology ,law.invention ,Bluetooth ,03 medical and health sciences ,Wearable Electronic Devices ,0302 clinical medicine ,law ,Medicine ,Wireless ,Humans ,In patient ,Electronics ,medicine.diagnostic_test ,business.industry ,Continuous monitoring ,Uncertainty ,Magnetic resonance imaging ,General Medicine ,021001 nanoscience & nanotechnology ,medicine.disease ,Cerebrospinal Fluid Shunts ,Hydrocephalus ,Epidermis ,0210 nano-technology ,business ,Rheology ,Wireless Technology ,030217 neurology & neurosurgery ,Shunt (electrical) ,Biomedical engineering - Abstract
Hydrocephalus is a common and costly neurological condition caused by the overproduction and/or impaired resorption of cerebrospinal fluid (CSF). The current standard of care, ventricular catheters (shunts), is prone to failure, which can result in nonspecific symptoms such as headaches, dizziness, and nausea. Current diagnostic tools for shunt failure such as computed tomography (CT), magnetic resonance imaging (MRI), radionuclide shunt patency studies (RSPSs), and ice pack–mediated thermodilution have disadvantages including high cost, poor accuracy, inconvenience, and safety concerns. Here, we developed and tested a noninvasive, skin-mounted, wearable measurement platform that incorporates arrays of thermal sensors and actuators for precise, continuous, or intermittent measurements of flow through subdermal shunts, without the drawbacks of other methods. Systematic theoretical and experimental benchtop studies demonstrate high performance across a range of practical operating conditions. Advanced electronics designs serve as the basis of a wireless embodiment for continuous monitoring based on rechargeable batteries and data transmission using Bluetooth protocols. Clinical studies involving five patients validate the sensor’s ability to detect the presence of CSF flow ( P = 0.012) and further distinguish between baseline flow, diminished flow, and distal shunt failure. Last, we demonstrate processing algorithms to translate measured data into quantitative flow rate. The sensor designs, fabrication schemes, wireless architectures, and patient trials reported here represent an advance in hydrocephalus diagnostics with ability to visualize flow in a simple, user-friendly mode, accessible to the physician and patient alike.
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- 2018
12. Low-Dose Gamma Knife Radiosurgery for Vestibular Schwannomas: Tumor Control and Cranial Nerve Function Preservation After 11 Gy
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Andrew J. Schumacher, Rishi R. Lall, Plato Lee, James P. Chandler, Samir V. Sejpal, Amit Ayer, Maryanne H. Marymont, Allan D. Nanney, Benjamin P. Liu, Bernard R. Bendok, Rohan R. Lall, and John A. Kalapurakal
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Low dose ,Gamma knife radiosurgery ,Cancer ,Neuroma ,medicine.disease ,Radiosurgery ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,Tumor progression ,030220 oncology & carcinogenesis ,medicine ,otorhinolaryngologic diseases ,Neurology (clinical) ,Progression-free survival ,sense organs ,Audiometry ,business ,030217 neurology & neurosurgery - Abstract
Objectives This study aims to report tumor control rates and cranial nerve function after low dose (11.0 Gy) Gamma knife radiosurgery (GKRS) in patients with vestibular schwannomas. Methods A retrospective chart review was performed on 30 consecutive patients with vestibular schwannomas treated from March 2004 to August 2010 with GKRS at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. The marginal dose for all patients was 11.0 Gy prescribed to the 50% isodose line. Median follow-up time was 42 months. The median treatment volume was 0.53 cm 3 . Hearing data were obtained from audiometry reports before and after radiosurgery. Results The actuarial progression free survival (PFS) based on freedom from surgery was 100% at 5 years. PFS based on freedom from persistent growth was 91% at 5 years. One patient experienced tumor progression requiring resection at 87 months. Serviceable hearing, defined as Gardner–Robertson score of I–II, was preserved in 50% of patients. On univariate and multivariate analyses, only higher mean and maximum dose to the cochlea significantly decreased the proportion of patients with serviceable hearing. Conclusion Vestibular schwannomas can be treated with low doses (11.0 Gy) of GKRS with good tumor control and cranial nerve preservation.
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- 2016
13. IL-27 Enhances LPS-Induced Proinflammatory Cytokine Production via Upregulation of TLR4 Expression and Signaling in Human Monocytes
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Amit Ayer, Bruce W. Banfield, Sameh Basta, Katrina Gee, and Christina Guzzo
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Lipopolysaccharides ,CD14 ,Immunology ,Dose-Response Relationship, Immunologic ,Priming (immunology) ,Cell Separation ,Biology ,Monocytes ,Proinflammatory cytokine ,Downregulation and upregulation ,Cell Line, Tumor ,Humans ,Immunology and Allergy ,RNA, Messenger ,Chemokine CCL4 ,STAT3 ,Cells, Cultured ,Chemokine CCL3 ,Inflammation ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Interleukins ,Cell Membrane ,Colocalization ,Acquired immune system ,Up-Regulation ,Cell biology ,Toll-Like Receptor 4 ,biology.protein ,TLR4 ,Inflammation Mediators ,Signal Transduction - Abstract
IL-27, which is produced by activated APCs, bridges innate and adaptive immunity by regulating the development of Th cells. Recent evidence supports a role for IL-27 in the activation of monocytic cells in terms of inflammatory responses. Indeed, proinflammatory and anti-inflammatory activities are attributed to IL-27, and IL-27 production itself is modulated by inflammatory agents such as LPS. IL-27 primes LPS responses in monocytes; however, the molecular mechanism behind this phenomenon is not understood. In this study, we demonstrate that IL-27 priming results in enhanced LPS-induced IL-6, TNF-α, MIP-1α, and MIP-1β expression in human primary monocytes. To elucidate the molecular mechanisms responsible for IL-27 priming, we measured levels of CD14 and TLR4 required for LPS binding. We determined that IL-27 upregulates TLR4 in a STAT3- and NF-κB–dependent manner. Immunofluorescence microscopy revealed enhanced membrane expression of TLR4 and more distinct colocalization of CD14 and TLR4 upon IL-27 priming. Furthermore, IL-27 priming enhanced LPS-induced activation of NF-κB family members. To our knowledge, this study is the first to show a role for IL-27 in regulating TLR4 expression and function. This work is significant as it reveals new mechanisms by which IL-27 can enhance proinflammatory responses that can occur during bacterial infections.
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- 2012
14. Advances in Neuroprotective Strategies: Potential Therapies for Intracerebral Hemorrhage
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Ivan S. Kotchetkov, Amit Ayer, Geoffrey Appelboom, Raqeeb Haque, Brian Y. Hwang, Christopher P. Kellner, E. Sander Connolly, Michael A Kellner, and Paul R. Gigante
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Stroke etiology ,Treatment outcome ,Anti-Inflammatory Agents ,Apoptosis ,Review ,Bioinformatics ,Neuroprotection ,medicine ,Animals ,Edema ,Humans ,cardiovascular diseases ,Stroke ,Cerebral Hemorrhage ,Intracerebral hemorrhage ,business.industry ,medicine.disease ,nervous system diseases ,Clinical trial ,Neuroprotective Agents ,Treatment Outcome ,Neurology ,Anesthesia ,Encephalitis ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,Signal Transduction - Abstract
Intracerebral hemorrhage (ICH) is associated with higher mortality and morbidity than any other form of stroke. However, there currently are no treatments proven to improve outcomes after ICH, and therefore, new effective therapies are urgently needed. Growing insight into ICH pathophysiology has led to the development of neuroprotective strategies that aim to improve the outcome through reduction of secondary pathologic processes. Many neuroprotectants target molecules or pathways involved in hematoma degradation, inflammation or apoptosis, and have demonstrated potential clinical benefits in experimental settings. We extensively reviewed the current understanding of ICH pathophysiology as well as promising experimental neuroprotective agents with particular focus on their mechanisms of action. Continued advances in ICH knowledge, increased understanding of neuroprotective mechanisms, and improvement in the ability to modulate molecular and pathologic events with multitargeting agents will lead to successful clinical trials and bench-to-bedside translation of neuroprotective strategies.
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- 2010
15. Intranasal Insulin Ameliorates Experimental Diabetic Neuropathy
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Amit Ayer, Thuhien Nguyen, Douglas W. Zochodne, Jose A. Martinez, George J. Francis, Jared M. Fine, Wei Liu, Cory Toth, William H. Frey, and Leah R. Hanson
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Blood Glucose ,Male ,medicine.medical_specialty ,Complications ,Hot Temperature ,Diabetic neuropathy ,Injections, Subcutaneous ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Mice, Inbred Strains ,Statement of Retraction ,Diabetes Mellitus, Experimental ,Iodine Radioisotopes ,Mice ,Nerve Fibers ,Diabetic Neuropathies ,Diabetes mellitus ,Internal medicine ,Reaction Time ,Internal Medicine ,medicine ,Animals ,Insulin ,Tissue Distribution ,Protein kinase B ,Administration, Intranasal ,Pancreatic hormone ,business.industry ,medicine.disease ,Streptozotocin ,Peripheral neuropathy ,Endocrinology ,Neuropathic pain ,Original Article ,business ,medicine.drug - Abstract
OBJECTIVE We hypothesized that intranasal insulin (I-I) delivery targets the nervous system while avoiding potential adverse systemic effects when compared with subcutaneous insulin (S-I) for experimental streptozotocin-induced diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS I-I or S-I at 0.87 IU daily or placebo were delivered in separate cohorts of diabetic and nondiabetic CD1 mice during 8 months of diabetes. Radiolabeled insulin detection was used to compare delivery and biodistribution for I-I and S-I. Biweekly behavioral testing and monthly electrophysiological and quantitative studies assessed progression of DPN. At and before end point, morphometric analysis of DRG, peripheral nerve, distal epidermal innervation, and specific molecular markers were evaluated. RESULTS Radiolabeled I-I resulted in more rapid and concentrated delivery to the spinal cord and DRG with less systemic insulin exposure. When compared with S-I or intranasal placebo, I-I reduced overall mouse mortality and sensory loss while improving neuropathic pain and electrophysiological/morphological abnormalities in diabetic mice. I-I restored mRNA and protein levels of phosphoinositide 3-kinase/Akt, cyclic AMP response element–binding protein, and glycogen synthase kinase 3β to near normal levels within diabetic DRGs. CONCLUSIONS I-I slows the progression of experimental DPN in streptozotocin mice, avoids adverse effects associated with S-I treatment, and prolongs lifespan when compared with S-I. I-I may be a promising approach for the treatment of DPN.
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- 2009
16. Update of retraction--Blockade of receptor for advanced glycation end products in a model of type 1 diabetic leukoencephalopathy. Diabetes. 19 November 2012 [Epub ahead of print]. DOI: 10.2337/db12-0317
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Cory Toth, Lingling Rong, Kevin Tse, David Han, Amit Ayer, Ann Marie Schmidt, Paul Lalli, Jemma Li, Kevin Xu, Jose A. Martinez, Natalia Rincon, and Geeta S. Singh
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medicine.medical_specialty ,business.industry ,Statement (logic) ,Endocrinology, Diabetes and Metabolism ,General surgery ,Receptor for Advanced Glycation End Products ,medicine.disease ,Blockade ,Leukoencephalopathy ,Disease Models, Animal ,Diabetes Mellitus, Type 1 ,Glycation ,Leukoencephalopathies ,Diabetes mellitus ,Internal Medicine ,medicine ,Animals ,Receptors, Immunologic ,business - Abstract
In January 2013, Diabetes retracted the above-listed article at the authors’ request. The original retraction statement appears below: The authors have formally requested to retract the above-titled paper, which was published online on 19 November 2012. The authors cite concerns that portions of Fig. 4 were submitted without knowledge of inherent errors or abnormalities that they recognized in retrospect after submission. Therefore, the article has been retracted so the authors can readdress the work and submit it for publication at a later time. The corresponding author requests to update …
- Published
- 2014
17. A ruptured infectious intracranial aneurysm with a combined fungal and bacterial etiology
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Joseph G. Adel, H. Hunt Batjer, Isaac Josh Abecassis, and Amit Ayer
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Subarachnoid hemorrhage ,medicine.drug_class ,Antibiotics ,Context (language use) ,Aneurysm, Ruptured ,medicine.disease_cause ,Infectious intracranial aneurysm ,Aneurysm ,Central Nervous System Fungal Infections ,medicine ,Humans ,cardiovascular diseases ,Pathogen ,business.industry ,Intracranial Aneurysm ,General Medicine ,Bacterial Infections ,Mycotic aneurysm ,Subarachnoid Hemorrhage ,medicine.disease ,Treatment Outcome ,Staphylococcus aureus ,Surgery ,Neurology (clinical) ,business - Abstract
1. IntroductionInfectious intracranial aneurysms (IIA) are rare, constituting0.7–5.4% of all intracranial aneurysms [1]. The vast majority – 86%in the preantibiotic era and now closer to 65% – are caused by bac-terial pathogens like Staphylococcus aureus and Streptoccus speciesin the context of a bacterial endocarditis arising from prostheticheart valvesorpotentialexposuretoinfectiousbloodstreamagentseither nosocomially or through intravenous (IV) drug injection [2].Currently, theterm“mycotic”isreservedforthosecausedbyafun-gal pathogen. Fungal pathogenicity due to the likes of Aspergillushas been reported over the past few decades due to the increasinguse of immunosuppressants, antibiotics, and steroids.We reportonanimmunocompetentpatientwhopresentedwitha somewhat typical clinical picture of bacterial endocarditis foundto have a ruptured 3mm saccular aneurysm in the right anteriorcerebral artery(ACA)atthebifurcationofA4andA5withassociatedsubarachnoid hemorrhage (SAH). Interestingly, pathology of theaneurysm revealed a fungal element. To our knowledge, this is the
- Published
- 2013
18. Clinical trials for neuroprotective therapies in intracerebral hemorrhage: a new roadmap from bench to bedside
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Amit Ayer, Brian Y. Hwang, E. Sander Connolly, and Geoffrey Appelboom
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Intracerebral hemorrhage ,medicine.medical_specialty ,Neurology ,business.industry ,General Neuroscience ,medicine.disease ,Neuroprotection ,Bench to bedside ,Clinical trial ,Basic research ,medicine ,cardiovascular diseases ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,Intensive care medicine ,Stroke - Abstract
The most deadly form of stroke, intracerebral hemorrhage (ICH) continues to puzzle researchers and produce substantial decrements in the quality of patients' lives. Intensive basic research has devised many agents with putative benefit in mitigating the devastating effects of ICH, but these therapies have been largely ineffective in the transition to clinical trials. However, a steady translational pipeline continues to provide new avenues of treatment that may be effective in the management of this condition. In this review, we aim to summarize the array of neuroprotective clinical trials and techniques used in the history of ICH, and delineate the progression of relevant research to date. Furthermore, we provide insight into methods that may allow for better translation of basic science advances into productive clinical trials.
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- 2012
19. Necrobiotic Cavitary Pulmonary Nodules: A Case Report
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Velez R, Sliesoraitis S, and Amit Ayer
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Pathology ,medicine.medical_specialty ,business.industry ,Medicine ,Omics ,Bioinformatics ,business - Published
- 2012
20. The sociopolitical history and physiological underpinnings of skull deformation
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Geoffrey Appelboom, Brian Y. Hwang, Matthew Piazza, Amit Ayer, Neil A. Feldstein, Richard C. E. Anderson, Michael M. McDowell, and Alexander Campbell
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Paleopathology ,Plagiocephaly ,media_common.quotation_subject ,Egypt, Ancient ,Anthropology, Physical ,Power (social and political) ,Politics ,State (polity) ,Perception ,Peru ,medicine ,Humans ,History, Ancient ,media_common ,Plagiocephaly, Nonsynostotic ,Skull ,General Medicine ,Mummies ,medicine.disease ,Epistemology ,Variety (cybernetics) ,Elite ,Surgery ,Neurology (clinical) ,Psychology ,Neuroscience - Abstract
Nichter and colleagues 21 suggested that the idiom “heads of state” might have derived from the practice of the political elite’s molding the heads of their offspring to differentiate themselves from the rest of a populace. Studies of human remains from ancient Peru and Egypt have not drawn attention to the political implications of artificial skull deformation, whether artistic or real. These perceptual or structural cranial characteristics can be derived from a variety of factors that will be elaborated upon throughout the course of this paper. First, physical evidence from ancient Peru and Egypt is reviewed. Second, the discussion draws attention to ways in which the politics of a society might help to explain the rationale behind ACD. Ancient Peruvian and Egyptian evidence suggests that physical or artistic manipulation of skulls was undertaken not just to reinforce social distinctions, but also to entrench political power. It is argued that approaching perceptions and portrayals of skulls could also complement discussions of artificially deformed crania. The techniques used in ACD will then be elaborated upon, with a discussion of the physiological basis, consequences, and treatments of plagiocephaly.
- Published
- 2010
21. Differential impact of diabetes and hypertension in the brain: adverse effects in grey matter
- Author
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Shaila Zaver, Kevin Xu, Christina Yang, Ann Marie Schmidt, Ursula I. Tuor, Ilia Poliakov, Jose A. Martinez, Alma Rosales-Hernandez, Amanda Herring, Amit Ayer, Natalia Rincon, Cory Toth, Alexandra Garven, and Adriena DeVisser
- Subjects
musculoskeletal diseases ,Male ,medicine.medical_specialty ,Grey matter ,Brain mapping ,Rats, Inbred WKY ,lcsh:RC321-571 ,Diabetes Mellitus, Experimental ,Diabetes Complications ,Atrophy ,Internal medicine ,Diabetes mellitus ,Rats, Inbred SHR ,medicine ,Animals ,cardiovascular diseases ,Cerebral perfusion pressure ,Cognitive decline ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Cerebral atrophy ,Brain Diseases, Metabolic ,medicine.disease ,Rats ,Rats, Zucker ,Disease Models, Animal ,Endocrinology ,medicine.anatomical_structure ,Neurology ,Brain size ,Hypertension ,Female ,Psychology - Abstract
Diabetes mellitus types 1 and 2 (DM1 and DM2) and/or hypertension (HTN) can contribute to cognitive decline, cerebral atrophy and white matter abnormalities in humans. Adult rat models of streptozotocin-induced DM1 and genetic strains of DM2 and HTN were used to investigate relative contributions of DM and HTN for alterations in cerebral structure and function as well as insulin receptor biology using cognitive testing, magnetic resonance imaging (MRI), and histological and molecular methods. The effects of DM1 or DM2 were generally similar. DM was associated with earlier onset of cognitive impairment than with HTN alone. DM was independently correlated with brain atrophy, whereas HTN had minimal effects on brain volume. The combination of DM and HTN led to identifiable mild hippocampal neuronal loss while either DM or HTN led to synaptic loss. Only DM led to downregulation of the insulin receptor pathways' activation. In contrast, only HTN was associated with vascular luminal reduction and restricted cerebral perfusion on MRI. The impacts of DM and HTN in the brain differ, while their separate contributions can lead to some additive adverse effects within rodent brain grey matter.
- Published
- 2010
22. Intranasal insulin prevents cognitive decline, cerebral atrophy and white matter changes in murine type I diabetic encephalopathy
- Author
-
Wei Q. Liu, Leah R. Hanson, Amit Ayer, Gordon W. Glazner, George J. Francis, Jose A. Martinez, Jared M. Fine, Kevin Xu, Cory Toth, Ursula I. Tuor, and William H. Frey
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,Drug Evaluation, Preclinical ,Nerve Tissue Proteins ,Hippocampus ,Diabetes Mellitus, Experimental ,Mice ,Diabetes mellitus ,Internal medicine ,Medicine ,Animals ,Insulin ,RNA, Messenger ,Cognitive decline ,Protein kinase B ,Administration, Intranasal ,Cerebral atrophy ,Type 1 diabetes ,business.industry ,Brain ,Human brain ,medicine.disease ,Delivery mode ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Endocrinology ,Diabetes Mellitus, Type 1 ,Gene Expression Regulation ,Encephalitis ,Neurology (clinical) ,Atrophy ,business ,Cognition Disorders - Abstract
Insulin deficiency in type I diabetes may lead to cognitive impairment, cerebral atrophy and white matter abnormalities. We studied the impact of a novel delivery system using intranasal insulin (I-I) in a mouse model of type I diabetes (streptozotocin-induced) for direct targeting of pathological and cognitive deficits while avoiding potential adverse systemic effects. Daily I-I, subcutaneous insulin (S-I) or placebo in separate cohorts of diabetic and non-diabetic CD1 mice were delivered over 8 months of life. Radio-labelled insulin delivery revealed that I-I delivered more rapid and substantial insulin levels within the cerebrum with less systemic insulin detection when compared with S-I. I-I delivery slowed development of cognitive decline within weekly cognitive/behavioural testing, ameliorated monthly magnetic resonance imaging abnormalities, prevented quantitative morphological abnormalities in cerebrum, improved mouse mortality and reversed diabetes-mediated declines in mRNA and protein for phosphoinositide 3-kinase (PI3K)/Akt and for protein levels of the transcription factors cyclic AMP response element binding protein (CREB) and glycogen synthase kinase 3beta (GSK-3beta) within different cerebral regions. Although the murine diabetic brain was not subject to cellular loss, a diabetes-mediated loss of protein and mRNA for the synaptic elements synaptophysin and choline acetyltransferase was prevented with I-I delivery. As a mechanism of delivery, I-I accesses the brain readily and slows the development of diabetes-induced brain changes as compared to S-I delivery. This therapy and delivery mode, available in humans, may be of clinical utility for the prevention of pathological changes in the diabetic human brain.
- Published
- 2008
23. Intranasal Insulin Ameliorates Experimental Diabetic Neuropathy. Diabetes 2009;58:934–945. DOI: 10.2337/db08-1287
- Author
-
William H. Frey, Wei Liu, George J. Francis, Thuhien Nguyen, Jared M. Fine, Amit Ayer, Leah R. Hanson, Cory Toth, Douglas W. Zochodne, and Jose A. Martinez
- Subjects
medicine.medical_specialty ,Diabetic neuropathy ,business.industry ,Endocrinology, Diabetes and Metabolism ,Insulin ,medicine.medical_treatment ,MEDLINE ,medicine.disease ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,Medicine ,business ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) - Abstract
The corresponding author has formally requested to retract the above-titled paper, which was published online on 9 January 2009. Table 1 has been duplicated from a prior publication …
- Published
- 2014
24. Blockade of receptor for advanced glycation end products in a model of type 1 diabetic leukoencephalopathy. Diabetes. 19 November 2012 [Epub ahead of print]
- Author
-
Natalia Rincon, Paul Lalli, Kevin Tse, David Han, LingLing Rong, Ann Marie Schmidt, Cory Toth, Amit Ayer, Geeta S. Singh, Jemma Li, Kevin Xu, and Jose A. Martinez
- Subjects
medicine.medical_specialty ,endocrine system diseases ,business.industry ,Endocrinology, Diabetes and Metabolism ,nutritional and metabolic diseases ,Statement of Retraction ,medicine.disease ,Streptozotocin ,Blockade ,Leukoencephalopathy ,Endocrinology ,Atrophy ,Downregulation and upregulation ,Glycation ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Cognitive decline ,business ,human activities ,medicine.drug - Abstract
Humans with type 1 diabetes mellitus (DM) are subject to the development of diabetic leukoencephalopathy (DLE) with cognitive decline, brain atrophy, and white matter abnormalities. We examined advanced glycation end products (AGE) and upregulation of their receptor (RAGE) stimulated by persistent hyperglycemia as a causative pathway, intervening with RAGE blockade in a murine DLE model of type 1 (streptozotocin) DM. Over 8 months, DM mice received intraperitoneal injections of soluble RAGE or placebo alongside non-DM mice and RAGE 2/2 mice. Cognitive testing and magnetic resonance imaging (T2, magnetization transfer, diffusion tensor imaging), neuronal and oligodendroglial counts, synaptic and myelin measures, and RAGE–nuclear factor (NF)-kB pathway assessment was performed serially. DM mice developed cognitive deficits after 8 to 20 weeks of DM, oligodendroglial loss after 3 months, brain atrophy after 5 months, loss of synaptic machinery and fractional anisotropy at 8 months, and RAGE–NF-kB pathway activation. DM mice receiving soluble RAGE and RAGE 2/2 DM mice were protected from most of these abnormalities. Although DM led to NF-k Bu pregulation, NF-kB–mediated gene transcription was downregulated at 8 months, possibly due to later upregulation of transcription repressors B-cell lymphoma 3-encoded protein and NF-k Bi nhibitor Ikbz. Blockade of RAGE has therapeutic importance in type 1D M–mediated DLE within the complex regulation of NF-kB.
- Published
- 2012
25. Neuropathy Due to Amiodarone: Schwann Cells Are the Target (IN1-1.005)
- Author
-
Zaid Jawad, Amit Ayer, Kelsey Hohol, and Cory Toth
- Subjects
business.industry ,Schwann cell ,Pharmacology ,medicine.disease ,Amiodarone ,Pathophysiology ,Myelin ,medicine.anatomical_structure ,Peripheral neuropathy ,In vivo ,medicine ,Neurology (clinical) ,Sciatic nerve ,business ,Sensory nerve ,medicine.drug - Abstract
Objective: This study evaluated the pathophysiology of amiodarone-induced peripheral neuropathy both in vivo and in vitro. Background Amiodarone has been long known to cause peripheral neuropathy, but the mechanism of action is uncertain. Design/Methods: We performed mouse dorsal root ganglia neuronal and Schwann cell cultures exposed to a dose range of amiodarone or placebo. We examined cellular viability, reactive oxygen species and mitochondrial function in vitro. Complementary in vivo studies with either systemic (intraperitoneal), intrathecal or near-nerve amiodarone or placebo delivery were performed in mice. Electrophysiological, structural and molecular studies were performed for dorsal root ganglia and sciatic nerves after 3 months of exposure to amiodarone or placebo. Results: There was no impact upon in vitro neurons with exposure to amiodarone. However, amiodarone was associated with a dose-related loss of Schwann cells in vitro, poor outcomes of myelination, and mitochondrial dysfunction. In vivo, amiodarone had mild impact when delivered intrathecally or systemically, but led to marked localized changes in nerve structure when delivered locally at the sciatic nerve. Local amiodarone produced slowing of nerve conduction velocities, loss of motor and sensory nerve potential amplitudes, and led to extensive myelin thinning and loss of large nerve fibers. Reactive oxygen species and mitochondrial dysfunction were detected in the local sciatic nerve with amiodarone delivery. Conclusions: Amiodarone appears to have a direct impact upon Schwann cells and their myelination function rather than any direct effect upon neuronal cells. Amiodarone–induced experimental peripheral neuropathy is a pure demyelinating neuropathy with direct effects upon Schwann cell well being. Supported by: Alberta Heritage Foundation for Medical Research. Disclosure: Dr. Hohol has nothing to disclose. Dr. Jawad has nothing to disclose. Dr. Ayer has nothing to disclose. Dr. Toth has received personal compensation for activities with Pfizer and Eli Lilly & Company as a speaker. Dr. Toth has received research support from Pfizer Inc, Valeant Pharmaceuticals International and Eli Lilly & Company.
- Published
- 2012
26. Neuropathy Due to Amiodarone: Schwann Cells Are the Target (P06.138)
- Author
-
Amit Ayer, Kelsey Hohol, Zaid Jawad, and Cory Toth
- Subjects
business.industry ,Schwann cell ,Pharmacology ,medicine.disease ,Amiodarone ,Pathophysiology ,Myelin ,medicine.anatomical_structure ,Peripheral neuropathy ,In vivo ,medicine ,Neurology (clinical) ,Sciatic nerve ,business ,Sensory nerve ,medicine.drug - Abstract
Objective: This study evaluated the pathophysiology of amiodarone-induced peripheral neuropathy both in vivo and in vitro. Background Amiodarone has been long known to cause peripheral neuropathy, but the mechanism of action is uncertain. Design/Methods: We performed mouse dorsal root ganglia neuronal and Schwann cell cultures exposed to a dose range of amiodarone or placebo. We examined cellular viability, reactive oxygen species and mitochondrial function in vitro. Complementary in vivo studies with either systemic (intraperitoneal), intrathecal or near-nerve amiodarone or placebo delivery were performed in mice. Electrophysiological, structural and molecular studies were performed for dorsal root ganglia and sciatic nerves after 3 months of exposure to amiodarone or placebo. Results: There was no impact upon in vitro neurons with exposure to amiodarone. However, amiodarone was associated with a dose-related loss of Schwann cells in vitro, poor outcomes of myelination, and mitochondrial dysfunction. In vivo, amiodarone had mild impact when delivered intrathecally or systemically, but led to marked localized changes in nerve structure when delivered locally at the sciatic nerve. Local amiodarone produced slowing of nerve conduction velocities, loss of motor and sensory nerve potential amplitudes, and led to extensive myelin thinning and loss of large nerve fibers. Reactive oxygen species and mitochondrial dysfunction were detected in the local sciatic nerve with amiodarone delivery. Conclusions: Amiodarone appears to have a direct impact upon Schwann cells and their myelination function rather than any direct effect upon neuronal cells. Amiodarone–induced experimental peripheral neuropathy is a pure demyelinating neuropathy with direct effects upon Schwann cell well being. Supported by: Alberta Heritage Foundation for Medical Research. Disclosure: Dr. Hohol has nothing to disclose. Dr. Jawad has nothing to disclose. Dr. Ayer has nothing to disclose. Dr. Toth has received personal compensation for activities with Pfizer and Eli Lilly & Company as a speaker. Dr. Toth has received research support from Pfizer Inc, Valeant Pharmaceuticals International and Eli Lilly & Company.
- Published
- 2012
27. Intranasal insulin prevents cognitive decline, cerebral atrophy and white matter changes in murine type I diabetic encephalopathy.
- Author
-
George J. Francis, Jose A. Martinez, Wei Q. Liu, Kevin Xu, Amit Ayer, Jared Fine, Ursula I. Tuor, Gordon Glazner, Leah R. Hanson, William H. Frey, and Cory Toth
- Subjects
PEOPLE with diabetes ,INSULIN ,NEUROLOGICAL disorders ,THERAPEUTICS ,CEREBRAL atrophy ,COGNITION disorders ,CYCLIC adenylic acid ,LABORATORY mice ,DISEASES - Abstract
Insulin deficiency in type I diabetes may lead to cognitive impairment, cerebral atrophy and white matter abnormalities. We studied the impact of a novel delivery system using intranasal insulin (I-I) in a mouse model of type I diabetes (streptozotocin-induced) for direct targeting of pathological and cognitive deficits while avoiding potential adverse systemic effects. Daily I-I, subcutaneous insulin (S-I) or placebo in separate cohorts of diabetic and non-diabetic CD1 mice were delivered over 8 months of life. Radio-labelled insulin delivery revealed that I-I delivered more rapid and substantial insulin levels within the cerebrum with less systemic insulin detection when compared with S-I. I-I delivery slowed development of cognitive decline within weekly cognitive/behavioural testing, ameliorated monthly magnetic resonance imaging abnormalities, prevented quantitative morphological abnormalities in cerebrum, improved mouse mortality and reversed diabetes-mediated declines in mRNA and protein for phosphoinositide 3-kinase (PI3K)/Akt and for protein levels of the transcription factors cyclic AMP response element binding protein (CREB) and glycogen synthase kinase 3β (GSK-3β) within different cerebral regions. Although the murine diabetic brain was not subject to cellular loss, a diabetes-mediated loss of protein and mRNA for the synaptic elements synaptophysin and choline acetyltransferase was prevented with I-I delivery. As a mechanism of delivery, I-I accesses the brain readily and slows the development of diabetes-induced brain changes as compared to S-I delivery. This therapy and delivery mode, available in humans, may be of clinical utility for the prevention of pathological changes in the diabetic human brain. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
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