Publications by authors named "Min-Hui Cui"

18 Publications

  • Page 1 of 1

Diffusion Tensor Imaging of the Evolving Response to Mild Traumatic Brain Injury in Rats.

J Exp Neurosci 2019 5;13:1179069519858627. Epub 2019 Jul 5.

The Gruss Magnetic Resonance Research Center, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.

Mild traumatic brain injury (mTBI), also known as concussion, is a serious public health challenge. Although most patients recover, a substantial minority suffers chronic disability. The mechanisms underlying mTBI-related detrimental effects remain poorly understood. Although animal models contribute valuable preclinical information and improve our understanding of the underlying mechanisms following mTBI, only few studies have used diffusion tensor imaging (DTI) to study the evolution of axonal injury following mTBI in rodents. It is known that DTI shows changes after human concussion and the role of delineating imaging findings in animals is therefore to facilitate understanding of related mechanisms. In this work, we used a rodent model of mTBI to investigate longitudinal indices of axonal injury. We present the results of 45 animals that received magnetic resonance imaging (MRI) at multiple time points over a 2-week period following concussive or sham injury yielding 109 serial observations. Overall, the evolution of DTI metrics following concussive or sham injury differed by group. Diffusion tensor imaging changes within the white matter were most noticeable 1 week following injury and returned to baseline values after 2 weeks. More specifically, we observed increased fractional anisotropy in combination with decreased radial diffusivity and mean diffusivity, in the absence of changes in axial diffusivity, within the white matter of the genu corpus callosum at 1 week post-injury. Our study shows that DTI can detect microstructural white matter changes in the absence of gross abnormalities as indicated by visual screening of anatomical MRI and hematoxylin and eosin (H&E)-stained sections in a clinically relevant animal model of mTBI. Whereas additional histopathologic characterization is required to better understand the neurobiological correlates of DTI measures, our findings highlight the evolving nature of the brain's response to injury following concussion.
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http://dx.doi.org/10.1177/1179069519858627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613065PMC
July 2019

Central IGF-1 protects against features of cognitive and sensorimotor decline with aging in male mice.

Geroscience 2019 04 10;41(2):185-208. Epub 2019 May 10.

Department of Molecular Pharmacology, Albert Einstein College of Medicine, Forchheimer Bldg, Rm 236, 1300 Morris Park Avenue, Bronx, NY, 10461, USA.

Disruptions in growth hormone/insulin-like growth factor-1 (GH/IGF-1) signaling have been linked to improved longevity in mice and humans. Nevertheless, while IGF-1 levels are associated with increased cancer risk, they have been paradoxically implicated with protection from other age-related conditions, particularly in the brain, suggesting that strategies aimed at selectively increasing central IGF-1 action may have favorable effects on aging. To test this hypothesis, we generated inducible, brain-specific (TRE-IGF-1 × Camk2a-tTA) IGF-1 (bIGF-1) overexpression mice and studied effects on healthspan. Doxycycline was removed from the diet at 12 weeks old to permit post-development brain IGF-1 overexpression, and animals were monitored up to 24 months. Brain IGF-1 levels were increased approximately twofold in bIGF-1 mice, along with greater brain weights, volume, and myelin density (P < 0.05). Age-related changes in rotarod performance, exercise capacity, depressive-like behavior, and hippocampal gliosis were all attenuated specifically in bIGF-1 male mice (P < 0.05). However, chronic brain IGF-1 failed to prevent declines in cognitive function or neurovascular coupling. Therefore, we performed a short-term intranasal (IN) treatment of either IGF-1 or saline in 24-month-old male C57BL/6 mice and found that IN IGF-1 treatment tended to reduce depressive (P = 0.09) and anxiety-like behavior (P = 0.08) and improve motor coordination (P = 0.07) and unlike transgenic mice improved motor learning (P < 0.05) and visuospatial and working memory (P < 0.05). These data highlight important sex differences in how brain IGF-1 action impacts healthspan and suggest that translational approaches that target IGF-1 centrally can restore cognitive function, a possibility that should be explored as a strategy to combat age-related cognitive decline.
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http://dx.doi.org/10.1007/s11357-019-00065-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544744PMC
April 2019

High fat diet aggravates cardiomyopathy in murine chronic Chagas disease.

Microbes Infect 2019 Jan - Feb;21(1):63-71. Epub 2018 Jul 31.

Department of Microbiology, Biochemistry and Molecular Genetics, Public Health Research Institute, New Jersey Medical School, Newark, USA. Electronic address:

Infection with Trypanosoma cruzi, the etiologic agent in Chagas disease, may result in heart disease. Over the last decades, Chagas disease endemic areas in Latin America have seen a dietary transition from the traditional regional diet to a Western style, fat rich diet. Previously, we demonstrated that during acute infection high fat diet (HFD) protects mice from the consequences of infection-induced myocardial damage through effects on adipogenesis in adipose tissue and reduced cardiac lipidopathy. However, the effect of HFD on the subsequent stages of infection - the indeterminate and chronic stages - has not been investigated. To address this gap in knowledge, we studied the effect of HFD during indeterminate and chronic stages of Chagas disease in the mouse model. We report, for the first time, the effect of HFD on myocardial inflammation, vasculopathy, and other types of dysfunction observed during chronic T. cruzi infection. Our results show that HFD perturbs lipid metabolism and induces oxidative stress to exacerbate late chronic Chagas disease cardiac pathology.
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http://dx.doi.org/10.1016/j.micinf.2018.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355378PMC
April 2019

Brain neurochemical and hemodynamic findings in the NY1DD mouse model of mild sickle cell disease.

NMR Biomed 2017 May 10;30(5). Epub 2017 Feb 10.

Gruss Magnetic Resonance Research Center, Albert Einstein College of Medicine, Bronx, New York, USA.

To characterize the cerebral profile associated with sickle cell disease (SCD), we used in vivo proton MRI and MRS to quantify hemodynamics and neurochemicals in the thalamus of NY1DD mice, a mild model of SCD, and compared them with wild-type (WT) control mice. Compared with WT mice, NY1DD mice at steady state had elevated cerebral blood flow (CBF) and concentrations of N-acetylaspartate (NAA), glutamate (Glu), alanine, total creatine and N-acetylaspartylglutamate. Concentrations of glutathione (GSH) at steady state showed a negative correlation with BOLD signal change in response to 100% oxygen, a marker for oxidative stress, and mean diffusivity assessed using diffusion-tensor imaging, a marker for edematous inflammation. In NY1DD mice, elevated basal CBF was correlated negatively with [NAA], but positively with concentration of glutamine ([Gln]). Immediately after experimental hypoxia (at reoxygenation after 18 hours of 8% O ), concentrations of NAA, Glu, GSH, Gln and taurine (Tau) increased only in NY1DD mice. [NAA], [Glu], [GSH] and [Tau] all returned to baseline levels two weeks after the hypoxic episode. The altered neurochemical profile in the NY1DD mouse model of SCD at steady state and following experimental hypoxia/reoxygenation suggests a state of chronic oxidative stress leading to compensatory cerebral metabolic adjustments.
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http://dx.doi.org/10.1002/nbm.3692DOI Listing
May 2017

Diet regulates liver autophagy differentially in murine acute Trypanosoma cruzi infection.

Parasitol Res 2017 Feb 16;116(2):711-723. Epub 2016 Dec 16.

Department of Microbiology, Biochemistry and Molecular Genetics, Public Health Research Institute, Rutgers state University, 225 Warren Street, Newark, NJ, 07103, USA.

Chagas disease is a tropical parasitic disease caused by the protozoan Trypanosoma cruzi, which affects about ten million people in its endemic regions of Latin America. After the initial acute stage of infection, 60-80% of infected individuals remain asymptomatic for several years to a lifetime; however, the rest develop the debilitating symptomatic stage, which affects the nervous system, digestive system, and heart. The challenges of Chagas disease have become global due to immigration. Despite well-documented dietary changes accompanying immigration, as well as a transition to a western style diet in the Chagas endemic regions, the role of host metabolism in the pathogenesis of Chagas disease remains underexplored. We have previously used a mouse model to show that host diet is a key factor regulating cardiomyopathy in Chagas disease. In this study, we investigated the effect of a high-fat diet on liver morphology and physiology, lipid metabolism, immune signaling, energy homeostasis, and stress responses in the murine model of acute T. cruzi infection. Our results indicate that in T. cruzi-infected mice, diet differentially regulates several liver processes, including autophagy, a stress response mechanism, with corresponding implications for human Chagas disease patients.
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http://dx.doi.org/10.1007/s00436-016-5337-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283091PMC
February 2017

Antagonistic effect of atorvastatin on high fat diet induced survival during acute Chagas disease.

Microbes Infect 2016 Nov 12;18(11):675-686. Epub 2016 Jul 12.

Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA; Department of Microbiology, Biochemistry and Molecular Genetics, Public Health Research Institute, Rutgers State University, 225 Warren Street, Newark, NJ 07103, USA. Electronic address:

Chagasic cardiomyopathy, which is seen in Chagas disease, is the most severe and life-threatening manifestation of infection by the kinetoplastid Trypanosoma cruzi. Adipose tissue and diet play a major role in maintaining lipid homeostasis and regulating cardiac pathogenesis during the development of Chagas cardiomyopathy. We have previously reported that T. cruzi has a high affinity for lipoproteins and that the invasion rate of this parasite increases in the presence of cholesterol, suggesting that drugs that inhibit cholesterol synthesis, such as statins, could affect infection and the development of Chagasic cardiomyopathy. The dual epidemic of diabetes and obesity in Latin America, the endemic regions for Chagas disease, has led to many patients in the endemic region of infection having hyperlipidemia that is being treated with statins such as atorvastatin. The current study was performed to examine mice fed on either regular or high fat diet for effects of atorvastatin on T. cruzi infection-induced myocarditis and to evaluate the effect of this treatment during infection on adipose tissue physiology and cardiac pathology. Atorvastatin was found to regulate lipolysis and cardiac lipidopathy during acute T. cruzi infection in mice and to enhance tissue parasite load, cardiac LDL levels, inflammation, and mortality in during acute infection. Overall, these data suggest that statins, such as atorvastatin, have deleterious effects during acute Chagas disease.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5071133PMC
http://dx.doi.org/10.1016/j.micinf.2016.06.006DOI Listing
November 2016

AAVP displaying octreotide for ligand-directed therapeutic transgene delivery in neuroendocrine tumors of the pancreas.

Proc Natl Acad Sci U S A 2016 Mar 16;113(9):2466-71. Epub 2016 Feb 16.

University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131; Division of Hematology/Oncology, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131

Patients with inoperable or unresectable pancreatic neuroendocrine tumors (NETs) have limited treatment options. These rare human tumors often express somatostatin receptors (SSTRs) and thus are clinically responsive to certain relatively stable somatostatin analogs, such as octreotide. Unfortunately, however, this tumor response is generally short-lived. Here we designed a hybrid adeno-associated virus and phage (AAVP) vector displaying biologically active octreotide on the viral surface for ligand-directed delivery, cell internalization, and transduction of an apoptosis-promoting tumor necrosis factor (TNF) transgene specifically to NETs. These functional attributes of AAVP-TNF particles displaying the octreotide peptide motif (termed Oct-AAVP-TNF) were confirmed in vitro, in SSTR type 2-expressing NET cells, and in vivo using cohorts of pancreatic NET-bearing Men1 tumor-suppressor gene KO mice, a transgenic model of functioning (i.e., insulin-secreting) tumors that genetically and clinically recapitulates the human disease. Finally, preclinical imaging and therapeutic experiments with pancreatic NET-bearing mice demonstrated that Oct-AAVP-TNF lowered tumor metabolism and insulin secretion, reduced tumor size, and improved mouse survival. Taken together, these proof-of-concept results establish Oct-AAVP-TNF as a strong therapeutic candidate for patients with NETs of the pancreas. More broadly, the demonstration that a known, short, biologically active motif can direct tumor targeting and receptor-mediated internalization of AAVP particles may streamline the potential utility of myriad other short peptide motifs and provide a blueprint for therapeutic applications in a variety of cancers and perhaps many nonmalignant diseases as well.
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http://dx.doi.org/10.1073/pnas.1525709113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4780640PMC
March 2016

No evidence for cell activation or brain vaso-occlusion with plerixafor mobilization in sickle cell mice.

Blood Cells Mol Dis 2016 Mar 21;57:67-70. Epub 2015 Dec 21.

Lindsley F. Kimball Research Institute, New York Blood Center, 310 East 67th St, New York, NY 10065, United States; Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, United States. Electronic address:

Gene therapy for sickle cell disease is currently in active trials. Collecting hematopoietic progenitor cells safely and effectively is challenging, however, because granulocyte colony stimulating factor, the drug used most commonly for mobilization, can cause life-threatening vaso-occlusion in patients with sickle cell disease, and bone marrow harvest requires general anesthesia and multiple hip bone punctures. Plerixafor is an inhibitor of the CXCR4 chemokine receptor on hematopoietic progenitor cells, blocking its binding to SDF-1 (CXCL12) on bone marrow stroma. In support of a clinical trial in patients with sickle cell disease of plerixafor mobilization (NCT02193191), we administered plerixafor to sickle cell mice and found that it mobilizes hematopoietic progenitor cells without evidence of concomitant cell activation or brain vaso-occlusion.
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http://dx.doi.org/10.1016/j.bcmd.2015.12.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806642PMC
March 2016

In vivo (1)H MRS and (31)P MRSI of the response to cyclocreatine in transgenic mouse liver expressing creatine kinase.

NMR Biomed 2015 Dec 9;28(12):1634-44. Epub 2015 Oct 9.

Gruss Magnetic Resonance Research Center, Albert Einstein College of Medicine, Bronx, NY, USA.

Hepatocyte transplantation has been explored as a therapeutic alternative to liver transplantation, but a means to monitor the success of the procedure is lacking. Published findings support the use of in vivo (31)P MRSI of creatine kinase (CK)-expressing hepatocytes to monitor proliferation of implanted hepatocytes. Phosphocreatine tissue level depends upon creatine (Cr) input to the CK enzyme reaction, but Cr measurement by (1)H MRS suffers from low signal-to-noise ratio (SNR). We examine the possibility of using the Cr analog cyclocreatine (CCr, a substrate for CK), which is quickly phosphorylated to phosphocyclocreatine (PCCr), as a higher SNR alternative to Cr. (1)H MRS and (31)P MRSI were employed to measure the effect of incremental supplementation of CCr upon PCCr, γ-ATP, pH and Pi /ATP in the liver of transgenic mice expressing the BB isoform of CK (CKBB) in hepatocytes. Water supplementation with 0.1% CCr led to a peak total PCCr level of 17.15 ± 1.07 mmol/kg wet weight by 6 weeks, while adding 1.0% CCr led to a stable PCCr liver level of 18.12 ± 3.91 mmol/kg by the fourth day of feeding. PCCr was positively correlated with CCr, and ATP concentration and pH declined with increasing PCCr. Feeding with 1% CCr in water induced an apparent saturated level of PCCr, suggesting that CCr quantization may not be necessary for quantifying expression of CK in mice. These findings support the possibility of using (31)P MRS to noninvasively monitor hepatocyte transplant success with CK-expressing hepatocytes.
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http://dx.doi.org/10.1002/nbm.3391DOI Listing
December 2015

In vivo proton MR spectroscopy of pancreatic neuroendocrine tumors in a multiple endocrine neoplasia type 1 conditional knockout mouse model.

Magn Reson Med 2015 Nov 13;74(5):1221-6. Epub 2014 Nov 13.

Department of Surgery, Albert Einstein College of Medicine, Bronx, New York, USA.

Purpose: MR spectroscopy (MRS) can improve diagnosis and follow treatment in cancer. However, no study has yet reported application of in vivo (1)H-MRS in malignant pancreatic lesions. This study quantitatively determined whether in vivo (1)H-MRS on multiple endocrine neoplasia type 1 (Men1) conditional knockout (KO) mice and their wild type (WT) littermates could detect differences in total choline (tCho) levels between tumor and control pancreas.

Methods: Relative tCho levels in pancreatic tumors or pancreata from KO and WT mice were determined using in vivo (1)H-MRS at 9.4 T. The levels of Cho-containing compounds were also quantified using in vitro (1)H-NMR on extracts of pancreatic tissues from KO and WT mice, respectively, and on extracts of pancreatic tissues from patients with pancreatic neuroendocrine tumors (PNETs).

Results: tCho levels measured by in vivo (1)H-MRS were significantly higher in PNETs from KO mice compared to the normal pancreas from WT mice. The elevated choline-containing compounds were also identified in pancreatic tumors from KO mice and tissues from patients with PNETs via in vitro (1)H-NMR.

Conclusion: These results indicate the potential use of tCho levels estimated via in vivo (1)H-MRS in differentiating malignant pancreatic tumors from benign tumors.
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http://dx.doi.org/10.1002/mrm.25529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430461PMC
November 2015

High fat diet modulates Trypanosoma cruzi infection associated myocarditis.

PLoS Negl Trop Dis 2014 Oct 2;8(10):e3118. Epub 2014 Oct 2.

Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America; Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America.

Background: Trypanosoma cruzi, the causative agent of Chagas disease, has high affinity for lipoproteins and adipose tissue. Infection results in myocarditis, fat loss and alterations in lipid homeostasis. This study was aimed at analyzing the effect of high fat diet (HFD) on regulating acute T. cruzi infection-induced myocarditis and to evaluate the effect of HFD on lipid metabolism in adipose tissue and heart during acute T. cruzi infection.

Methodology/principal Findings: CD1 mice were infected with T. cruzi (Brazil strain) and fed either a regular control diet (RD) or HFD for 35 days following infection. Serum lipid profile, tissue cholesterol levels, blood parasitemia, and tissue parasite load were analyzed to evaluate the effect of diet on infection. MicroPET and MRI analysis were performed to examine the morphological and functional status of the heart during acute infection. qPCR and immunoblot analysis were carried out to analyze the effect of diet on the genes involved in the host lipid metabolism during infection. Oil red O staining of the adipose tissue demonstrated reduced lipolysis in HFD compared to RD fed mice. HFD reduced mortality, parasitemia and cardiac parasite load, but increased parasite load in adipocytes. HFD decreased lipolysis during acute infection. Both qPCR and protein analysis demonstrated alterations in lipid metabolic pathways in adipose tissue and heart in RD fed mice, which were further modulated by HFD. Both microPET and MRI analyses demonstrated changes in infected RD murine hearts which were ameliorated by HFD.

Conclusion/significance: These studies indicate that Chagasic cardiomyopathy is associated with a cardiac lipidpathy and that both cardiac lipotoxicity and adipose tissue play a role in the pathogenesis of Chagas disease. HFD protected mice from T. cruzi infection-induced myocardial damage most likely due to the effects of HFD on both adipogenesis and T. cruzi infection-induced cardiac lipidopathy.
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http://dx.doi.org/10.1371/journal.pntd.0003118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183439PMC
October 2014

Hypoglycemia-associated autonomic failure is prevented by opioid receptor blockade.

J Clin Endocrinol Metab 2009 Sep 30;94(9):3372-80. Epub 2009 Jun 30.

Department of Medicine, Division of Endocrinology and Metabolism, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.

Context: Repeated hypoglycemia is associated with hypoglycemia-associated autonomic failure (HAAF), a syndrome of defective counterregulation.

Objective: HAAF increases the risk of severe hypoglycemia in diabetes, although its mechanism remains unresolved. Because beta-endorphin influences the autonomic response to hypoglycemia via opioid receptor activation, we hypothesized that it is also involved in the pathogenesis of HAAF.

Research Design And Methods: We asked whether opioid receptor blockade during antecedent hypoglycemia (60 mg/dl) on d 1 would prevent development of HAAF on d 2 in eight nondiabetic subjects (five males, 3 females; age, 28 +/- 3.5 yr; body mass index, 24.2 +/- 2.1 kg/m(2)). On four occasions, d 1 was: 1) two 90-min hypoglycemic clamps (N-); 2) two 90-min hypoglycemic clamps plus naloxone (N+); 3) two euglycemic 90-min clamps (C); or 4) two euglycemic 90-min clamps plus naloxone (C+).

Results: Day 1 hypoglycemia caused marked deterioration of d 2 hormonal responses to hypoglycemia, consistent with HAAF-i.e. decreased plasma epinephrine, norepinephrine, and glucagon compared to control (C) (374 +/- 71 vs. 810 +/- 94, 307 +/- 65 vs. 686 +/- 98, and 71 +/- 9 vs. 93 +/- 4 pg/ml, respectively, P < 0.01), as well as in endogenous glucose production (24 vs. 163%; P < 0.01). In contrast, naloxone on d 1 completely prevented the defective counterregulatory responses; epinephrine, norepinephrine, and glucagon (852 +/- 82, 769 +/- 77, and 98 +/- 7 pg/ml) and endogenous glucose production recovery (167%) were identical to those after d 1 euglycemia (P < NS for all). Infusion of naloxone alone during euglycemia on d 1 (C+) had no effect on d 2 responses.

Conclusions: These data suggest that the opioid signaling system is a promising target for further studies to prevent HAAF.
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http://dx.doi.org/10.1210/jc.2009-0882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2741720PMC
September 2009

Depression is an early disease manifestation in lupus-prone MRL/lpr mice.

J Neuroimmunol 2009 Feb 3;207(1-2):45-56. Epub 2009 Jan 3.

The Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.

Many lupus patients develop neuropsychiatric manifestations, including cognitive dysfunction, depression, and anxiety. However, it is not clear if neuropsychiatric lupus is a primary disease manifestation, or is secondary to non-CNS disease. We found that MRL/lpr lupus-prone mice exhibited significant depression-like behavior already at 8 weeks of age, despite normal visual working memory, locomotor coordination and social preference. Moreover, depression was significantly correlated with titers of autoantibodies against DNA, NMDA receptors and cardiolipin. Our results indicate that lupus mice develop depression and CNS dysfunction very early in the course of disease, in the absence of substantial pathology involving other target organs.
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http://dx.doi.org/10.1016/j.jneuroim.2008.11.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2675630PMC
February 2009

Increased intrahepatic triglyceride is associated with peripheral insulin resistance: in vivo MR imaging and spectroscopy studies.

Am J Physiol Endocrinol Metab 2007 Dec 2;293(6):E1663-9. Epub 2007 Oct 2.

Gruss MRRC Rm. No. 213, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA.

Recent studies have indicated that the mass/content of intramyocellular lipid (IMCL), intrahepatic triglyceride (IHTG), visceral fat (VF), and even deep abdominal subcutaneous fat (SF) may all be correlated with insulin resistance. Since simultaneous measurements of these parameters have not been reported, the relative strength of their associations with insulin action is not known. Therefore, the goals of this study were 1) to simultaneously measure IMCL, IHTG, VF, and abdominal SF in the same nondiabetic individuals using noninvasive (1)H-magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) and 2) to examine how these fat stores are correlated with systemic insulin sensitivity as measured by whole body glucose disposal (R(d)) during euglycemic-hyperinsulinemic clamp studies. Positive correlations were observed among IMCL, IHTG, and VF. There were significant inverse correlations between whole body R(d) and both IMCL and VF. Notably, there was a particularly tight inverse correlation between IHTG and whole body R(d) (r = -0.86, P < 0.001), consistent with an association between liver fat and peripheral insulin sensitivity. This novel finding suggests that hepatic triglyceride accumulation has important systemic consequences that may adversely affect insulin sensitivity in other tissues.
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http://dx.doi.org/10.1152/ajpendo.00590.2006DOI Listing
December 2007

Cross contamination of intramyocellular lipid signals through loss of bulk magnetic susceptibility effect differences in human muscle using (1)H-MRSI at 4 T.

J Appl Physiol (1985) 2007 Oct 2;103(4):1290-8. Epub 2007 Aug 2.

Department of Medicine, Albert Einstein College of Medicine, Gruss MRRC Rm. 205, 1300 Morris Park Ave., Bronx, NY 10461, USA.

Cross contamination of intramyocellular lipid (IMCL) signals through loss of bulk magnetic susceptibility (BMS) differences was detected in human muscles using proton magnetic resonance spectroscopic imaging ((1)H-MRSI) at 4 T by varying nominal voxel sizes on healthy subjects. In soleus muscle the IMCL content estimated in 1.00-ml-sized voxels was 15% and 30% higher than that in 0.25-ml voxels for nonobese (P < 0.05) and obese (P < 0.01) subjects, respectively, whereas no effect was observed on IMCL estimation in tibialis posterior (TP) and tibialis anterior (TA) regions for different voxel sizes. The unbiased 0.25-ml voxel size (1)H-MRSI method was applied to measure IMCL content in nonobese sedentary (NOB-Sed), moderately trained (Ath), sedentary obese (OB), and Type 2 diabetic mellitus (DM) subjects. IMCL content in soleus was greatest in OB, with decreasing content in DM, Ath, and NOB-Sed, respectively (12.6 +/- 1.6, 9.7 +/- 1.8, 7.4 +/- 1.0, 4.9 +/- 0.5 mmol/kg wet wt; P < 0.05 by ANOVA; P < 0.05 OB vs. NOB-Sed or Ath). In TA, IMCL was equivalently elevated in DM and OB, which was higher than in Ath or NOB-Sed, respectively (4.2 +/- 0.4 and 4.2 +/- 0.7 vs. 2.7 +/- 0.5 and 1.5 +/- 0.3 mmol/kg wet wt; ANOVA, P < 0.05; P < 0.05 DM or OB vs. NOB-Sed). We conclude that IMCL content is overestimated when voxel size exceeds 0.25 ml despite measurement by optimized high-resolution (1)H-MRSI at high field. When IMCL is measured unbiased by concomitant obesity, we find that it is strongly influenced by muscle type, training status, and the presence of obesity and Type 2 diabetes.
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http://dx.doi.org/10.1152/japplphysiol.01088.2006DOI Listing
October 2007

Role of hepatic glycogen breakdown in defective counterregulation of hypoglycemia in intensively treated type 1 diabetes.

Diabetes 2006 Mar;55(3):659-66

Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA.

Impairment of hypoglycemic counterregulation in intensively treated type 1 diabetes has been attributed to deficits in counterregulatory hormone secretion. However, because the liver plays a critical part in recovery of plasma glucose, abnormalities in hepatic glycogen metabolism per se could also play an important role. We quantified the contribution of net hepatic glycogenolysis during insulin-induced hypoglycemia in 10 nondiabetic subjects and 7 type 1 diabetic subjects (HbA1c 6.5 +/- 0.2%) using 13C nuclear magnetic resonance spectroscopy, during 2 h of either hyperinsulinemic euglycemia (plasma glucose 92 +/- 4 mg/dl) or hypoglycemia (plasma glucose 58 +/- 3 mg/dl). In nondiabetic subjects, hypoglycemia was associated with a brisk counterregulatory hormone response (plasma epinephrine 246 +/- 38 vs. 2,785 +/- 601 pmol/l during hypoglycemia, plasma norepinephrine 1.9 +/- 0.2 vs. 2.5 +/- 0.3 nmol/l, and glucagon 38 +/- 7 vs. 92 +/- 17 pg/ml, respectively, P < 0.001 in all), and a relative increase in endogenous glucose production (EGP 0.83 +/- 0.14 mg x kg(-1) x min(-1) during euglycemia yet approximately 50% higher with hypoglycemia [1.30 +/- 0.20 mg x kg(-1) x min(-1)], P < 0.001). Net hepatic glycogen content declined progressively during hypoglycemia to 22 +/- 3% below baseline (P < 0.024). By the final 30 min of hypoglycemia, hepatic glycogen fell from 301 +/- 14 to 234 +/- 10 mmol/l (P < 0.001) and accounted for approximately 100% of EGP. In marked contrast, after an overnight fast, hepatic glycogen concentration in type 1 diabetic subjects (215 +/- 23 mmol/l) was significantly lower than in nondiabetic subjects (316 +/- 19 mmol/l, P < 0.001). Furthermore, the counterregulatory response to hypoglycemia was significantly reduced with small increments in plasma epinephrine and norepinephrine (126 +/- 22 vs. 448 +/- 16 pmol/l in hypoglycemia and 0.9 +/- 0.3 vs. 1.6 +/- 0.3 nmol/l, respectively, P < 0.05 for both) and no increase in plasma glucagon. EGP decreased during hypoglycemia with no recovery (1.3 +/- 0.5 vs. 1.2 +/- 0.3 mg x kg(-1) x min(-1) compared with euglycemia, P = NS), and hepatic glycogen concentration did not change significantly with hypoglycemia. We conclude that glycogenolysis accounts for the majority of EGP during the first 90 min of hypoglycemia in nondiabetic subjects. In intensively treated type 1 diabetes, despite some activation of counterregulation, hypoglycemia failed to stimulate hepatic glycogen breakdown or activation of EGP, factors that may contribute to the defective counterregulation seen in such patients.
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http://dx.doi.org/10.2337/diabetes.55.03.06.db05-0849DOI Listing
March 2006

Microwave absorption by nanostructural ferric oxide encapsulated within MCM-41.

Chem Commun (Camb) 2003 Jun(12):1432-3

Center for Analysis of Structures and Interfaces, Chemistry Department, The City College of New York, Convent Ave. at 138th St., New York, NY 10031, USA.

A new functional material with nonzero microwave absorption ability at zero applied magnetic field results from loading MCM-41 to a high percentage by weight with ferric oxide.
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http://dx.doi.org/10.1039/b303224hDOI Listing
June 2003

A new route to alumoxane gel: a versatile precursor to gamma-alumina and alumina-based ceramic oxides.

J Am Chem Soc 2003 Apr;125(14):4010-1

Department of Chemical Engineering, Chemistry & Material Science, Polytechnic University, 6 Metrotech Center, Brooklyn, New York 11201, USA.

We present a new route for the preparation of gamma-alumina and YAG nanoparticles. Metal salts of ethylhexanoic acids provide good solubility in hydrocarbon solvents and allow efficient ultrasonication. The sonication product is an alumioxane gel, which can reversibly collapse and reform, depending on the solvent used. The dried gel nanoparticles are calcined at temperatures significantly lower than those used in conventional syntheses, resulting in gamma-alumina nanoparticles. This is due to the complete mixing of elements at the atomic level and the small size of the formed nanoparticles.
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http://dx.doi.org/10.1021/ja0213625DOI Listing
April 2003