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1.
Microb Ecol ; 70(1): 168-74, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25592636

ABSTRACT

Formation of magnetite in anaerobic sediments is thought to be enhanced by the activities of iron-reducing bacteria. Geobacter has been implicated as playing a major role, as in culture its cells are often associated with extracellular magnetite grains. We studied the bacterial community associated with magnetite grains in sediment of a freshwater pond in South Korea. Magnetite was isolated from the sediment using a magnet. The magnetite-depleted fraction of sediment was also taken for comparison. DNA was extracted from each set of samples, followed by PCR for 16S bacterial ribosomal RNA (rRNA) gene and HiSeq sequencing. The bacterial communities of the magnetite-enriched and magnetite-depleted fractions were significantly different. The enrichment of three abundant operational taxonomic units (OTUs) suggests that they may either be dependent upon the magnetite grain environment or may be playing a role in magnetite formation. The most abundant OTU in magnetite-enriched fractions was Geobacter, bolstering the case that this genus is important in magnetite formation in natural systems. Other major OTUs strongly associated with the magnetite-enriched fraction, rather than the magnetite-depleted fraction, include a Sulfuricella and a novel member of the Betaproteobacteria. The existence of distinct bacterial communities associated with particular mineral grain types may also be an example of niche separation and coexistence in sediments and soils, which cannot usually be detected due to difficulties in separating and concentrating minerals.


Subject(s)
Ferrosoferric Oxide/analysis , Geologic Sediments/microbiology , Microbiota/genetics , Ponds/microbiology , Base Sequence , DNA Primers/genetics , Geobacter/genetics , Geologic Sediments/chemistry , Molecular Sequence Data , RNA, Ribosomal, 16S/genetics , Real-Time Polymerase Chain Reaction , Republic of Korea , Sequence Analysis, DNA , Species Specificity
2.
Endocrinology ; 154(9): 3366-76, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23825123

ABSTRACT

Despite the emerging importance of fibroblast growth factor 21 (FGF21) as a metabolic hormone regulating energy balance, its direct effects on renal function remain unexplored. FGF21 was injected ip daily for 12 weeks into db/db mice. Compared with control vehicle injection, FGF21 treatment significantly improved lipid profiles and insulin resistance and resulted in significantly higher serum adiponectin levels. In contrast, serum insulin and 8-isoprostane levels were significantly decreased. Interestingly, FGF21 and its receptor components in the kidneys were found to be significantly up-regulated in db/db mice, which suggests an FGF21-resistant state. FGF21 treatment significantly down-regulated FGF21 receptor components and activated ERK phosphorylation. FGF21 administration also markedly decreased urinary albumin excretion and mesangial expansion and suppressed profibrotic molecule synthesis. Furthermore, FGF21 improved renal lipid metabolism and oxidative stress injury. In cultured renal cells, FGF21 was mainly expressed in mesangial cells, and knockdown of FGF21 expression by stealth small interfering RNA further aggravated high-glucose-induced profibrotic cytokine synthesis in mesangial cells. Our results suggest that FGF21 improves insulin resistance and protects against renal injury through both improvement of systemic metabolic alterations and antifibrotic effects in type 2 diabetic nephropathy. Targeting FGF21 could therefore provide a potential candidate approach for a therapeutic strategy in type 2 diabetic nephropathy.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Diabetic Retinopathy/prevention & control , Fibroblast Growth Factors/therapeutic use , Hypoglycemic Agents/therapeutic use , Insulin Resistance , Kidney/drug effects , Adiponectin/blood , Adiponectin/metabolism , Adipose Tissue, White/drug effects , Adipose Tissue, White/metabolism , Animals , Crosses, Genetic , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/pathology , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/metabolism , Fibroblast Growth Factors/pharmacology , Gene Expression Regulation/drug effects , Hyperlipidemias/complications , Hyperlipidemias/prevention & control , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/metabolism , Hypoglycemic Agents/pharmacology , Kidney/cytology , Kidney/metabolism , Kidney/pathology , Lipid Peroxidation/drug effects , MAP Kinase Signaling System/drug effects , Male , Mesangial Cells/cytology , Mesangial Cells/drug effects , Mesangial Cells/metabolism , Mesangial Cells/pathology , Mice , Mice, Inbred C57BL , Mice, Mutant Strains , Oxidative Stress/drug effects , Receptors, Fibroblast Growth Factor/biosynthesis , Receptors, Fibroblast Growth Factor/metabolism , Recombinant Proteins/metabolism , Recombinant Proteins/pharmacology , Recombinant Proteins/therapeutic use
3.
Endocrinology ; 154(6): 2144-55, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23568555

ABSTRACT

Chronic inflammation caused by high glucose and high free fatty acid (FFA) concentrations is a major contributor to the pathogenesis of type 2 diabetes. Recent evidence suggests that activation of Toll-like receptor (TLR) signaling induces peripheral insulin resistance and mediates central insulin and leptin resistance. In this study, we investigated the renal effects of TLR4 signaling blockade in type 2 diabetic mice. Eight-week-old db/db mice were treated for 12 weeks with (S,R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid (GIT27), which targets macrophages through the inhibition of TLR4- and TLR2/6-mediated signaling pathways. Although GIT27 treatment improved glycemic control and insulin tolerance, which is associated with a lower lipid profile, it did not impact body weight or food consumption. GIT27 treatment also markedly decreased urinary albumin excretion, decreased proinflammatory cytokine synthesis, improved tissue lipid metabolism, induced oxidative stress, and improved glomerulosclerosis compared with the control db/db group. In cultured podocytes and adipocytes, high glucose levels with FFA stimulation increased TLR4 expression and proinflammatory cytokine synthesis, but the effects were abolished by GIT27 treatment. In addition, knockdown of TLR4 expression by stealth small interfering RNA abolished FFA-induced proinflammatory cytokine synthesis in cultured podocytes. In conclusion, our results suggest that GIT27 treatment improves insulin resistance and protects against the renal injury that occurs in type 2 diabetic nephropathy through both metabolic and antiglomerulosclerotic mechanisms. These results suggest that TLR pathway inhibition might play a direct protective role in diabetic kidney disease.


Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Kidney/metabolism , Signal Transduction/physiology , Toll-Like Receptor 4/physiology , 3T3-L1 Cells , Acetates/pharmacology , Adipocytes/drug effects , Adipocytes/metabolism , Albuminuria/metabolism , Albuminuria/prevention & control , Animals , Blotting, Western , Cells, Cultured , Cytokines/metabolism , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Fatty Acids, Nonesterified/pharmacology , Gene Expression/drug effects , Glucose/pharmacology , Inflammation Mediators/metabolism , Insulin Resistance , Kidney/drug effects , Lipid Metabolism/drug effects , Male , Mice , Mice, Inbred C57BL , Oxazoles/pharmacology , Podocytes/drug effects , Podocytes/metabolism , RNA Interference , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , Signal Transduction/genetics , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism
4.
Endocrinology ; 153(3): 1387-96, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22234468

ABSTRACT

The endocannabinoid system is important in the pathogenesis of obesity-related metabolic disorders. However, the effect of inhibiting the endocannabinoid system in type 2 diabetic nephropathy is unclear. Therefore, we examined the effect of the cannabinoid (CB)1 receptor antagonist, SR141716, on insulin resistance and diabetic nephropathy in db/db mice. Six-week-old db/db mice were treated with the CB1-specific antagonist SR141716 (10 mg/kg · d) for 3 months. Treatment with SR141716 significantly improved insulin resistance and lipid abnormalities. Concomitantly, CB1 antagonism improved cardiac functional and morphological abnormality, hepatic steatosis, and phenotypic changes of adipocytes into small differentiated forms, associated with increased adiponectin expression and decreased lipid hydroperoxide levels. CB1 receptor was overexpressed in diabetic kidneys, especially in podocytes. Treatment with the SR141716 markedly decreased urinary albumin excretion and mesangial expansion and suppressed profibrotic and proinflammatory cytokine synthesis. Furthermore, SR141716 improved renal lipid metabolism and decreased urinary 8-isoprostane levels, renal lipid hydroperoxide content, and renal lipid content. In cultured podocytes, high-glucose stimulation increased CB1 receptor expression, and SR141716 treatment abolished high-glucose-induced up-regulation of collagen and plasminogen activator inhibitor-1 synthesis. Additionally, knockdown of CB1 receptor expression by stealth small interfering RNA abolished high-glucose-induced sterol-regulatory element-binding protein-1 expression in podocytes. These findings suggest that CB1 blockade improves insulin resistance and protect against renal injury through both metabolic and antifibrotic effects in type 2 diabetic nephropathy. Targeting CB1 blockade could therefore provide a new therapeutic target to prevent type 2 diabetic nephropathy.


Subject(s)
Diabetic Nephropathies/drug therapy , Insulin Resistance , Lipid Metabolism , Receptor, Cannabinoid, CB1/antagonists & inhibitors , Animals , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Gene Expression Regulation , Glucose/metabolism , Lipids/chemistry , Male , Mice , Mice, Inbred C57BL , Piperidines/pharmacology , Podocytes/cytology , Pyrazoles/pharmacology , RNA Interference , RNA, Small Interfering/metabolism , Receptor, Cannabinoid, CB1/physiology , Rimonabant
5.
J Int Med Res ; 40(6): 2370-80, 2012.
Article in English | MEDLINE | ID: mdl-23321195

ABSTRACT

OBJECTIVE: Clinicians hesitate to perform thoracic paravertebral blockade (TPVB) in children due to the potential high risk of adverse effects. No paediatric anatomical guidelines for TPVB exist. This study aimed to estimate the appropriate depth and distance for safe needle positioning in children. METHODS: The depth (D) from the skin to the paravertebral space and the distance (A) from the spinous process to the needle entry point on the skin were measured using chest computed tomography (CT) in children aged between 1 and 9 years. Correlations between age, gender, weight, height, body mass index (BMI) and each of the anatomical measurements were analysed. RESULTS: Each measurement correlated significantly with age, weight and height, but not with BMI (n = 373 children). Measurements A and D could be calculated by: A = 13.56 + (0.33 × age [years]) + (0.06 × weight [kg]) + 0.47 × (gender [female = 0, male = 1]); and D = 17.49 - (0.35 × age [years]) + (0.55 × weight [kg]). CONCLUSION: These anatomical guidelines for TPVB are recommended to help prevent anaesthetic complications such as pneumothorax, when ultrasonography and CT are unavailable.


Subject(s)
Anesthetics/administration & dosage , Nerve Block/methods , Thoracic Vertebrae/anatomy & histology , Anesthesia/adverse effects , Anesthetics/adverse effects , Body Mass Index , Body Weight , Child , Child, Preschool , Female , Humans , Infant , Male , Multimodal Imaging , Nerve Block/adverse effects , Patient Positioning , Pneumothorax , Positron-Emission Tomography , Thoracic Vertebrae/diagnostic imaging , Tomography, X-Ray Computed , Ultrasonography
6.
Neuroscience ; 170(3): 711-21, 2010 Oct 27.
Article in English | MEDLINE | ID: mdl-20674684

ABSTRACT

To elucidate whether interleukin-18 (IL-18) or interferon-γ (IFN-γ) participates in neurodegeneartion, we investigated the changes in IL-18 and IFN-γ systems within the rat hippocampus following status epilepticus (SE). In non-SE induced animals, IL-18, IL-18 receptor α (IL-18Rα), IFN-γ and IFN-γ receptor α (IFN-γRα) immunoreactivity was not detected in the hippocampus. Following SE, IL-18 immunoreactivity was increased in CA1-3 pyramidal cells as well as dentate granule cells. IL-18 immunoreactivity was also up-regulated in astrocytes and microglia/macrophages. IL-18Rα immunoreactivity was detected in astrocytes and microglia/macrophages. IFN-γ immunoreactivity was detected only in astrocytes within all regions of the hippocampus. IFN-γRα immunoreactivity was increased in neurons as well as astrocytes. Intracerebroventricular infusions of recombinant rat IL-18 or IFN-γ alleviated SE-induced neuronal damages, while neutralization of IL-18, IFN-γ or their receptors aggravated them, as compared to saline-infused animals. These findings suggest that astroglial-mediated IFN-γ pathway in response to IL-18 induction may play an important role in alleviation of SE-induced neuronal damages.


Subject(s)
Hippocampus/drug effects , Interferon-gamma/pharmacology , Nerve Degeneration/prevention & control , Neurons/drug effects , Status Epilepticus/pathology , Animals , Astrocytes/metabolism , Disease Models, Animal , Hippocampus/pathology , Infusions, Intraventricular , Interferon-gamma/administration & dosage , Interferon-gamma/metabolism , Interleukin-18/administration & dosage , Interleukin-18/metabolism , Interleukin-18 Receptor alpha Subunit/metabolism , Male , Microglia/metabolism , Nerve Degeneration/metabolism , Neurons/metabolism , Neurons/pathology , Pilocarpine , Rats , Rats, Sprague-Dawley , Receptors, Interferon/metabolism , Recombinant Proteins , Status Epilepticus/chemically induced , Up-Regulation , Interferon gamma Receptor
7.
Am J Transplant ; 9(9): 2024-33, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19624561

ABSTRACT

This study was performed to investigate the effect of sirolimus (SRL) on cyclosporine (CsA)-induced pancreatic islet dysfunction in rats. Three separate studies were performed. First, diabetogenic effect of SRL was evaluated with three different doses (0.15, 0.3 and 0.6 mg/kg). Second, rats were treated with SRL (0.3 mg/kg) with or without CsA (15 mg/kg) for 4 weeks. Third, rats were treated with CsA for 4 weeks, and then switched to SRL for 4 weeks. The effect of SRL on CsA-induced pancreatic islet dysfunction was evaluated by an intraperitoneal glucose tolerance test, plasma insulin concentration, HbA1c level, HOMA-R index, immunohistochemistry of insulin and pancreatic beta islet cell mass. The SRL treatment increased blood glucose concentration in a dose-dependent manner. The combined treatment with SRL and CsA increased blood glucose concentration, Hemoglobin A1c (HbA1c) level, HOMA-R [fasting insulin (mU/mL) x fasting glucose (mmol/L)]/22.5] index and decreased plasma insulin concentration, immunoreactivity of insulin and pancreatic beta islet cell mass compared with rats treated with CsA. CsA withdrawal for 4 weeks improved pancreatic beta-cell function and structure. However, conversion from CsA to SRL further increased blood glucose levels compared with the rats converted from vehicle to SRL. The results of our study demonstrate that SRL is diabetogenic and aggravates CsA-induced pancreatic islet dysfunction.


Subject(s)
Cyclosporine/adverse effects , Diabetes Mellitus, Experimental/drug therapy , Islets of Langerhans/drug effects , Sirolimus/pharmacology , 8-Hydroxy-2'-Deoxyguanosine , Animals , Blood Glucose/metabolism , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/pharmacology , Diabetes Mellitus, Experimental/pathology , Dose-Response Relationship, Drug , Glycated Hemoglobin/metabolism , Immunohistochemistry/methods , Immunosuppressive Agents/adverse effects , Insulin/blood , Male , Rats , Rats, Sprague-Dawley
8.
Neurology ; 71(6): 426-9, 2008 Aug 05.
Article in English | MEDLINE | ID: mdl-18678825

ABSTRACT

BACKGROUND: Anti-GQ1b antibody has been found in Miller Fisher syndrome (MFS), Guillain-Barré syndrome (GBS) with ophthalmoplegia, Bickerstaff brainstem encephalitis (BBE), and acute ophthalmoplegia without ataxia (AO). The aim of this study was to determine the clinical features of AO associated with anti-GQ1b antibody. METHODS: We retrospectively collected 34 patients with anti-GQ1b antibody syndrome. Of these patients, 31 patients had ophthalmoplegia. The patients with ophthalmoplegia were classified into MFS (n = 13), AO (n = 11), GBS with ophthalmoplegia (n = 6), and BBE (n = 1). We analyzed clinical features and patterns of external and internal ophthalmoplegia of AO, and neuro-ophthalmologic findings were compared with those of other anti-GQ1b syndromes with ophthalmoplegia. RESULTS: AO was observed in 11 (32.4%) of the 34 patients with anti-GQ1b antibody. External ophthalmoparesis was present in all the patients and included mixed horizontal-vertical (n = 7), pure horizontal (n = 3), and pure vertical gaze palsy (n = 1). Binocular involvement was common, but unilateral ophthalmoparesis was also observed in 27.3%. Other findings included ptosis (n = 5, 45.5%) and internal ophthalmoplegia (n = 6, 54.5%). Other anti-GQ1b antibody syndromes had prominent neurologic signs including ataxia, weakness, and facial palsy in addition to ophthalmoplegia. The patterns of neuro-ophthalmologic findings did not differ between AO and other anti-GQ1b antibody syndromes with ophthalmoplegia. CONCLUSIONS: Acute ophthalmoplegia (AO) commonly occurs in anti-GQ1b antibody syndrome and manifests as various combinations of external and internal ophthalmoplegia. Internal ophthalmoplegia is fairly common and unilateral involvement may occur in AO.


Subject(s)
Autoantibodies/blood , Gangliosides/immunology , Ophthalmoplegia/epidemiology , Ophthalmoplegia/immunology , Acute Disease , Adolescent , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Syndrome
9.
Bone ; 42(2): 405-13, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18053788

ABSTRACT

Osteomalacia is characterized by hypomineralization of the bone associated with increased water content. In this work we evaluate the hypotheses that 1) 3D solid-state magnetic resonance imaging (MRI) of (31)P (SSI-PH) and (1)H (SSI-WATER) of cortical bone can quantify the key characteristics of osteomalacia induced by low-phosphate diet; and 2) return to normophosphatemic diet (NO) results in recovery of these indices to normal levels. Twenty female five-week old rabbits were divided into four groups. Five animals were fed a normal diet for 8 weeks (NOI); five a hypophosphatemic diet (0.09%) for the same period to induce osteomalacia (HYI). To examine the effect of recovery from hypophosphatemia an additional five animals received a hypophosphatemic diet for 8 weeks, after which they were returned to a normal diet for 6 weeks (HYII). Finally, five animals received a normal diet for the entire 14 weeks (NOII). The NOI and HYI animals were sacrificed after 8 weeks, the NOII and HYII groups after 14 weeks. Cortical bone was extracted from the left and right tibiae of all the animals. Water content was measured by SSI-WATER and by a previously reported spectroscopic proton-deuteron nuclear magnetic resonance (NMR) exchange technique (NMR-WATER), phosphorus content by SSI-PH. All MRI and NMR experiments were performed on a 9.4 T spectroscopy/micro-imaging system. Degree of mineralization of bone (DMB) was measured by micro-CT and elastic modulus and ultimate strength by 3-point bending. The following parameters were lower in the hypophosphatemic group: phosphorus content measured by SSI-PH (9.5+/-0.4 versus 11.1+/-0.3 wt.%, p<0.0001), ash content (63.9+/-1.7 versus 65.4+/-1.1 wt.%, p=0.05), ultimate strength, (96.3+/-16.0 versus 130.7+/-6.4 N/mm(2), p=0.001), and DMB (1115+/-28 versus 1176+/-24 mg/cm(3), p=0.003); SSI-WATER: 16.1+/-1.5 versus 14.4+/-1.1 wt.%, p=0.04; NMR-WATER: 19.0+/-0.6 versus 17.4+/-1.2 wt.%, p=0.01. Return to a normophosphatemic diet reduced or eliminated these differences (SSI-PH: 9.5+/-0.9 versus 10.6+/-0.8 wt.%, p=0.04; DMB: 1124+/-31 versus 1137+/-10 mg/cm(3), p=0.2; US: 95.6+/-18.6 versus 103.9+/-7.5 N/mm(2), p=0.2; SSI-WATER: 12.4+/-0.6 versus 12.2+/-0.3 wt.%, p=0.3) indicating recovery of the mineral density close to normal levels. Phosphorus content measured by SSI-PH was significantly correlated with DMB measured by micro-CT (r(2)=0.47, p=0.001) as well as with ultimate strength (r(2)=0.54, p=0.0004). The results show that the methods presented have potential for in situ assessment of mineralization and water, both critical to the bone's mechanical behavior.


Subject(s)
Bone Density , Osteomalacia/pathology , Animals , Biomechanical Phenomena , Disease Models, Animal , Female , Magnetic Resonance Imaging , Rabbits
10.
Cephalalgia ; 27(10): 1101-8, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17725653

ABSTRACT

A paroxysmal stabbing or icepick-like headache in the multiple nerve dermatomes, especially involving both trigeminal and cervical nerves, has not been fully explained or classified by the International Classification of Headache Disorder, 2(nd) Edition (ICHD-II). Of patients with acute-onset paroxysmal stabbing headache who had visited the Hallym University Medical Center during the last four years, 28 subjects with a repeated stabbing headache involving multiple dermatomes at the initial presentation or during the course were prospectively enrolled. All patients were neurologically and otologically symptom free. A coincidental involvement of both trigeminal and cervical nerve dermatomes included seven cases. Six cases involved initially the trigeminal and then cervical nerve dermatomes. Five cases showed an involvement of the cervical and then trigeminal nerve dermatomes. The remaining patients involved multiple cervical nerve branches (the lesser occipital, greater occipital and greater auricular). Pain lasted very shortly and a previous history of headache with the same nature was reported in 13 cases. Preceding symptom of an infection and physical and/or mental stress were manifested in seven and six subjects, respectively. All patients showed a self-limited benign course and completely recovered within a few hours to 30 days. Interestingly, a seasonal gradient in occurrence of a stabbing headache was found in this study. A paroxysmal stabbing headache manifested on multiple dermatomes can be explained by the characteristics of pain referral, and may be considered to be a variant of primary stabbing headache or occipital neuralgia.


Subject(s)
Head/innervation , Headache Disorders, Primary/classification , Headache Disorders, Primary/physiopathology , Neck/innervation , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neck Pain/etiology , Pain Measurement , Trigeminal Nerve
11.
Neuroscience ; 147(1): 136-45, 2007 Jun 15.
Article in English | MEDLINE | ID: mdl-17507170

ABSTRACT

Riluzole, an anti-amyotrophic lateral sclerosis drug, known to decrease presynaptic glutamate release, is viewed as a candidate supplementary medication for epilepsy. In the present study, we compared the effects of riluzole and valproate (VPA) in the pilocarpine-induced limbic seizure model and in the gamma-hydroxybutyrate lactone (GBL)-induced absence seizure model. We applied immunohistochemical study for vesicular transporter 1 (VGLUT1) and extracellular recording in the rat dentate gyrus of both pilocarpine- and GBL-induced seizure models to measure effects of riluzole and VPA. Both VPA and riluzole treatments reduced VGLUT1 immunoreactivity. Riluzole treatment completely inhibited pre-ictal spikes and spike-wave discharges in the pilocarpine- and GBL-induced epilepsy models, whereas VPA partially inhibited these phenomena. In both seizure models, the anti-epileptic effects of VPA and riluzole are basically related to anti-glutamatergic (reducing field excitatory postsynaptic potential slope and excitability ratio), not GABAergic (paired-pulse inhibition) effect. Riluzole was more effective at reducing seizure activity in both epilepsy models than VPA. These results suggest that riluzole is a potential antiepileptic drug with activity against limbic seizure and absence seizure.


Subject(s)
Anticonvulsants/pharmacology , Riluzole/pharmacology , Seizures/drug therapy , Status Epilepticus/drug therapy , Valproic Acid/pharmacology , Vesicular Glutamate Transport Protein 1/metabolism , Animals , Dentate Gyrus/drug effects , Dentate Gyrus/metabolism , Disease Models, Animal , Epilepsy, Absence/chemically induced , Epilepsy, Absence/drug therapy , Epilepsy, Absence/metabolism , Excitatory Postsynaptic Potentials/drug effects , Limbic System/drug effects , Limbic System/metabolism , Limbic System/physiopathology , Male , Pilocarpine , Rats , Rats, Sprague-Dawley , Seizures/chemically induced , Seizures/metabolism , Sodium Oxybate , Status Epilepticus/chemically induced , Status Epilepticus/metabolism , Vesicular Glutamate Transport Protein 1/drug effects
12.
J Magn Reson ; 186(1): 17-25, 2007 May.
Article in English | MEDLINE | ID: mdl-17280847

ABSTRACT

q-Space imaging is capable of providing quantitative geometrical information of structures at cellular resolution. However, the size of restrictions that can be probed hinges on available gradient amplitude and places very high demands on gradient performance. In this work we describe the design and construction of a small, high-amplitude (50 T/m) z-gradient coil, interfaced with a commercial 9.4 T microimaging system. We also describe a method to calibrate the coil for quantitative measurements of molecular diffusion at very high-gradient amplitudes. Calibration showed linear current response up to 50 T/m, with a gain=1.255 T/m/A. The z-gradient coil was combined with the commercial x- and y-gradients for tri-axial imaging, and its performance was demonstrated by ADC maps of free water and by q-space experiments on water sequestered around polystyrene microspheres (4.5 microm diameter), which showed the expected diffraction peak. In addition, diffusion-weighted images of a fixed mouse spinal cord illustrated the capability of this coil for quantitative imaging of tissue microstructure.


Subject(s)
Diffusion Magnetic Resonance Imaging/instrumentation , Diffusion Magnetic Resonance Imaging/standards , Image Enhancement/instrumentation , Image Enhancement/standards , Spinal Cord/anatomy & histology , Spinal Cord/physiology , Transducers , Animals , Calibration , Computer-Aided Design , Equipment Design , Equipment Failure Analysis , Magnetics , Mice , Reproducibility of Results , Sensitivity and Specificity , United States
13.
Magn Reson Med ; 56(5): 946-52, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17041893

ABSTRACT

In osteomalacia decreased mineralization reduces the stiffness and static strength of bone. We hypothesized that hypomineralization in osteomalacic bone could be quantified by solid-state (31)P magnetic resonance imaging (SS-MRI). Hypomineralization was measured with a 3D radial imaging technique at 162 MHz (9.4T) in rabbit cortical bone of hypophosphatemic (HY) and normophosphatemic (NO) animals. The results were compared with those obtained by quantitative micro-CT (micro-CT) and (31)P solution NMR. 3D images of 277 microm isotropic voxel size were obtained in 1.7 hr with SNR approximately 9. Mineral content was lower in the HY relative to the NO group (SS-MRI: 9.48 +/- 0.4 vs. 11.15 +/- 0.31 phosphorus wet wt %, P < 0.0001; micro-CT: 1114.6 +/- 28.3 vs. 1175.7 +/- 23.5 mg mineral/cm(3); P = 0.003). T(1) was shorter in the HY group (47.2 +/- 3.5 vs. 54.1 +/- 2.7 s, P = 0.004), which suggests that relaxation occurs via a dipole-dipole (DD) mechanism involving exchangeable water protons, which are more prevalent in bone from osteomalacic animals.


Subject(s)
Femur/metabolism , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy/methods , Osteomalacia/diagnosis , Osteomalacia/metabolism , Phosphorus/analysis , Tibia/metabolism , Anatomy, Cross-Sectional/methods , Animals , Biomarkers/analysis , Bone Density , Feasibility Studies , Femur/pathology , Humans , Imaging, Three-Dimensional/methods , Phosphorus Radioisotopes , Rabbits , Reproducibility of Results , Sensitivity and Specificity , Tibia/pathology
14.
Eur J Neurol ; 13(7): 742-8, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16834704

ABSTRACT

To understand the characteristics of posterior circulation ischemic stroke (PCS) in the Korean population better, we retrospectively reviewed the data from the Hallym Stroke Registry (HSR). We analyzed the demographic features, risk factors, stroke subtypes, lesion distributions and clinical outcomes of 591 consecutive patients with PCS, enrolled in HSR between January 1996 and July 2002. PCS was 39.8% of all ischemic strokes. Mean age of PCS patients was 63.4 years and 55.7% were men. Hypertension was the most common risk factor (69.9%). However, potential cardioembolic sources were found only in 11.0%. The most frequent stroke subtype was large artery disease (50.0%), followed by small vessel disease (33.8%). Only 5.2% of patients were classified as affected with cardioembolism. The most common location of infarcts was in the middle territory (36.5%), followed by distal (28.1%), proximal (19.0%), and multiple territories (16.4%). The hospital mortality rate (4.1%) and discharge outcome of PCS were comparable with those of the anterior circulation stroke (ACS). In conclusion, the etiology and lesion topography of PCS in the Korean population appeared to be different from those of the Caucasians.


Subject(s)
Brain Ischemia/epidemiology , Brain/pathology , Infarction, Posterior Cerebral Artery/epidemiology , Infarction, Posterior Cerebral Artery/etiology , Aged , Brain Ischemia/classification , Brain Ischemia/complications , Brain Ischemia/pathology , Diagnostic Imaging/methods , Female , Humans , Korea/epidemiology , Male , Middle Aged , Registries , Retrospective Studies , Risk Factors
15.
NMR Biomed ; 19(2): 198-208, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16475206

ABSTRACT

Collateral circulation plays a major role in maintaining cerebral blood flow (CBF) in patients with internal carotid artery (ICA) stenosis. CBF can remain normal despite severe ICA stenosis, making the benefit of carotid endarterectomy (CEA) or stenting difficult to assess. Before and after surgery, we assessed CBF supplied through the ipsilateral (stenotic) or contralateral ICA individually with a novel hemisphere-selective arterial spin-labeling (ASL) perfusion MR technique. We further explored the relationship between CBF and ICA obstruction ratio (OR) acquired with a multislice black-blood imaging sequence. For patients with unilateral ICA stenosis (n = 19), conventional bilateral labeling did not reveal interhemispheric differences. With unilateral labeling, CBF in the middle cerebral artery (MCA) territory on the surgical side from the ipsilateral supply (53.7 +/- 3.3 ml/100 g/min) was lower than CBF in the contralateral MCA territory from the contralateral supply (58.5 +/- 2.7 ml/100 g/min), although not statistically significant (p = 0.09). The ipsilateral MCA territory received significant (p = 0.02) contralateral supply (7.0 +/- 2.7 ml/100 g/min), while ipsilateral supply to the contralateral side was not reciprocated. After surgery (n = 11), ipsilateral supply to the MCA territory increased from 57.3 +/- 5.7 to 67.3 +/- 5.4 ml/100 g/min (p = 0.03), and contralateral supply to the ipsilateral MCA territory decreased. The best predictor of increased CBF on the side of surgery was normalized presurgical ipsilateral supply (r(2) = 0.62, p = 0.004). OR was less predictive of change, although the change in normalized contralateral supply was negatively correlated with OR(excess) (=OR(ipsilateral) - OR(contralateral)) (r(2) = 0.58, p = 0.006). The results demonstrate the effect of carotid artery stenosis on blood supply to the cerebral hemispheres, as well as the relative role of collateral pathways before surgery and redistribution of blood flow through these pathways after surgery. Unilateral ASL may better predict hemodynamic surgical outcome (measured by improved perfusion) than ICA OR.


Subject(s)
Brain/blood supply , Carotid Stenosis/diagnosis , Carotid Stenosis/surgery , Endarterectomy, Carotid , Intracranial Arteriosclerosis/diagnosis , Intracranial Arteriosclerosis/surgery , Magnetic Resonance Imaging/methods , Aged , Blood Flow Velocity , Brain/pathology , Carotid Stenosis/etiology , Cerebrovascular Circulation , Female , Humans , Intracranial Arteriosclerosis/complications , Male , Prognosis , Severity of Illness Index , Spin Labels , Treatment Outcome
16.
Biomaterials ; 27(3): 473-84, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16112728

ABSTRACT

This paper describes a method for preparing substrates with micropatterns of positive guidance cues for the purpose of stimulating the growth of neurons. This method uses an oxidizing potential, applied to a micropattern of indium tin oxide in the presence of pyrrole and polyglutamic acid, to electrodeposit a matrix consisting of polypyrrole doped with polyglutamic acid. The resulting matrix subsequently can be modified with positive guidance cues via standard amide coupling reactions. Cells adhered to the micropatterned substrates can be stimulated electrically by the underlying electrodeposited matrix while they are in contact with positive guidance cues. This method can be extended to include both positive and negative guidance cues in a variety of combinations. To demonstrate the suitability of this method in the context of nerve guidance, dorsal root ganglia were grown in the presence of a micropatterned substrate whose surface was modified with molecules such as polylysine, laminin, or both. Cell adhesion and neurite extension were found to occur almost exclusively in areas where positive guidance cues were attached. This method is easy to execute and is of general utility for fundamental studies on the behavior of neurons in the presence of complex combinations of guidance cues as well as advanced bioelectronic devices such as neuronal networks.


Subject(s)
Guided Tissue Regeneration/methods , Neurites/chemistry , Polyglutamic Acid/chemistry , Polymers/chemistry , Pyrroles/chemistry , Animals , Cell Count , Cell Enlargement , Electrochemistry , Ganglia, Spinal/cytology , Ganglia, Spinal/physiology , Laminin/chemistry , Nerve Regeneration , Neurites/physiology , Neurofilament Proteins/analysis , Neurons/chemistry , Neurons/cytology , Neurons/physiology , Polylysine/chemistry , Rats , Spectrophotometry, Infrared
17.
Heart ; 92(4): 499-502, 2006 Apr.
Article in English | MEDLINE | ID: mdl-15994913

ABSTRACT

OBJECTIVE: To examine the safety and applicability of off pump coronary artery bypass surgery (OPCAB) in patients with significant left ventricular dysfunction and to discuss the clinical implications for the surgical methods. DESIGN: Retrospective study. SETTING: Tertiary care university affiliated referral centre. PARTICIPANTS: 353 consecutive patients with preoperative left ventricular ejection fraction < or = 35% who underwent coronary artery bypass over a three year period. MAIN OUTCOME MEASURES: Postoperative morbidity and mortality. METHODS: 144 patients operated by OPCAB were compared with 209 patients operated by conventional coronary artery bypass. Multivariate and univariate analyses were performed on the pre- and postoperative variables to predict risk factors associated with hospital morbidity and mortality. RESULTS: Patients in the OPCAB group were more likely to be women and to have congestive heart failure, chronic obstructive pulmonary disease, hypertension, and diabetes; patients in the on pump group were more likely to have had a recent myocardial infarction and to have more severe angina pectoris and an urgent/emergent status. The groups did not differ significantly in length of stay, major postoperative complication rates, or mortality. Comparison of the impact of the procedures on surgical methods over time showed an increase in the use of OPCAB (13% to 67%), without any impact on morbidity or mortality. CONCLUSIONS: OPCAB is feasible and applicable for patients with depressed left ventricular function. This high risk group can potentially benefit from the off pump approach.


Subject(s)
Coronary Artery Bypass, Off-Pump , Ventricular Dysfunction, Left/surgery , Aged , Coronary Artery Bypass, Off-Pump/adverse effects , Coronary Artery Bypass, Off-Pump/methods , Coronary Artery Bypass, Off-Pump/trends , Feasibility Studies , Female , Humans , Length of Stay , Male , Middle Aged , Postoperative Complications/etiology , Retrospective Studies , Risk Factors , Treatment Outcome
18.
Bone ; 35(1): 266-76, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15207767

ABSTRACT

The mechanical competence of trabecular bone is significantly determined, next to material density, by its three-dimensional (3D) structure. Recent advances in micromagnetic resonance imaging (micro-MRI) acquisition and processing techniques allow the 3D trabecular structure to be analyzed in vivo at peripheral sites such as the distal radius and tibia. The practicality of micro-MRI-based noninvasive virtual bone biopsy (VBB) for longitudinal studies of patients hinges on the reproducibility of the derived structural parameters, which largely determine the size of the effect that can be detected at a given power and significance level. In this paper, the reproducibility of micro-MRI-derived trabecular bone structure measures was examined by performing repeat studies in six healthy subjects in whom the distal aspects of the radius and tibia were scanned with a 3D spin-echo sequence at 137 x 137 x 410 microm3 voxel size. Bone volume fraction (BV/TV) and digital topological analysis (DTA) structural parameters including the topological bone surface-to-curve ratio (SCR) and topological erosion index (TEI) were evaluated after subjecting the raw images to a cascade of processing steps. The average coefficient of variation was 4-7% and was comparable for the two anatomic sites and for all parameters measured. The reliability expressed in terms of the intraclass correlation coefficient ranged from 0.95 to 0.97 in the radius and 0.68 to 0.92 in the tibia. Error analysis based on simulations suggests involuntary patient motion, primarily rotation, to be the chief source of imprecision, followed by failure to accurately match the analysis volumes in repeat studies.


Subject(s)
Radius/anatomy & histology , Tibia/anatomy & histology , Adult , Female , Humans , Magnetic Resonance Imaging , Male , Reproducibility of Results
19.
J Biomech Eng ; 124(2): 253-8, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12002136

ABSTRACT

The function of soft connective tissues is frequently characterized by quantifying tissue strain (e.g., during joint motion). Conventional techniques for quantifying tendon and ligament strain typically provide surface measures, using markers, stain lines or instrumentation that may influence the tissue. An alternative approach is to quantify intratendinous strain by applying texture correlation analysis to magnetic resonance (MR) images. This paper reports the accuracy and reproducibility of this approach by (1) assessing the reproducibility of MR images, (2) assessing texture correlation accuracy using simulated displacements, and (3) comparing texture correlation measures of displacement and strain from MR images to conventional techniques.


Subject(s)
Image Enhancement/methods , Ligaments, Articular/physiology , Magnetic Resonance Imaging/methods , Shoulder Joint/physiology , Tendons/physiology , Cadaver , Elasticity , Humans , Pattern Recognition, Automated , Reproducibility of Results , Sensitivity and Specificity , Statistics as Topic , Stress, Mechanical
20.
J Struct Biol ; 135(3): 281-93, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11722168

ABSTRACT

Protease HslV and ATPase HslU form an ATP-dependent protease in bacteria. We have previously determined the structure of the components of this protease. In the case of HslU, the structure was derived from HslU-HslV cocrystals, combining phase information from MAD and the previously determined HslV model. Whereas the structures of the components were confirmed in detail by later structures, the quaternary arrangement of HslV and HslU was not reproduced in later crystal forms. In a recent communication to this journal, Wang attempted a reinterpretation of our original data to account for this difference. In response, we demonstrate that difference Pattersons, difference Fouriers, molecular replacement calculations, R factors, and omit maps all support our original analysis and prove that the suggested reinterpretation is false by these criteria. In particular, we show that our crystals are essentially untwinned and that only the originally reported quaternary arrangement of HslV and HslU particles is consistent with the experimental data. We finally demonstrate that Wang's newly introduced R(tpart) method to predict translational corrections for a subset of the unit cell contents is systematically flawed.


Subject(s)
Adenosine Triphosphatases/chemistry , Endopeptidases/chemistry , Heat-Shock Proteins , Serine Endopeptidases , ATP-Dependent Proteases , Binding Sites , Crystallography, X-Ray , Escherichia coli/enzymology , Mercury , Models, Molecular , Protein Structure, Quaternary
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