Publications by Year: 2008

2008

Stubenrauch C, Tessendorf R, Salvati A, Topgaard D, Sottmann T, Strey R, Lynch I. Gelled polymerizable microemulsions. 2. Microstructure. Langmuir. 2008;24(16):8473–82. doi:10.1021/la800918g
Using bicontinuous microemulsions as templates opens a new field for the design of novel structures and thus novel materials, but has significant challenges due to the very small composition and temperature windows in which microemulsions are bicontinuous. In previous work we had shown that we can take a ternary base system (water-n-dodecane—C 13/15E 5), add monomer and cross-linker ( N-isopropylacrylamide and N, N’-methylenebisacrylamide) to the water phase, and add a gelator (12-hydroxyoctadecanoic acid) to the oil phase while remaining in the one-phase region of the phase diagram. It was also possible to allow the gelator to form an organogel by changing the temperature such that we crossed the sol—gel line, which fell within the one-phase region. In this work, we show conclusively that addition of the monomers and the gelator does not affect the microemulsion microstructure and that, even in the gelled state, the polymerizable microemulsion is indeed bicontinuous. 1H NMR self-diffusion, conductivity, and small-angle neutron scattering measurements all confirm the bicontinuous nature of the gelled polymerizable microemulsion.
Leal C \ilia, Rögnvaldsson S, Fossheim S, Nilssen EA, Topgaard D. Dynamic and structural aspects of PEGylated liposomes monitored by NMR. J Colloid Interface Sci. 2008;325(2):485–93. doi:10.1016/j.jcis.2008.05.051
Proton-detected NMR diffusion and (31)P NMR chemical shifts/bandwidths measurements were used to investigate a series of liposomal formulations where size and PEGylation extent need to be controlled for ultrasound mediated drug release. The width of the (31)P line is sensitive to aggregate size and shape and self-diffusion (1)H NMR conveys information about diffusional motion, size, and PEGylation extent. Measurements were performed on the formulations at their original pH, osmolality, and lipid concentration. These contained variable amounts of PEGylated phospholipid (herein referred to as PEG-lipid) and cholesterol. At high levels of PEG-lipid (11.5 and 15 mol%) the self-diffusion (1)H NMR revealed the coexistence of two entities with distinct diffusion coefficients: micelles (1.3 to 3x10(-11) m(2)/s) and liposomes (approximately 5x10(-12) m(2)/s). The (31)P spectra showed a broad liposome signal and two distinct narrow lines that were unaffected by temperature. The narrow lines arise from mixed micelles comprising both PEG-lipids and phospholipids. The echo decay in the diffusion experiments could be described as a sum of exponentials revealing that the exchange of PEG-lipid between liposomes and micellar aggregates is slower than the experimental observation time. For low amounts of PEG-lipid (1 and 4.5 mol%) the (31)P spectra consisted of a broad signal typically obtained for liposomes and the diffusion data were best described by a single exponential decay attributed solely to liposomes. For intermediate amounts of PEG-lipid (8 mol%), micellization started to occur and the diffusion data could no longer be fitted to a single or bi-exponential decay. Instead, the data were best described by a log-normal distribution of diffusion coefficients. The most efficient PEG-lipid incorporation in liposomes (about 8 mol%) was achieved for lower molecular weight PEG (2000 Da vs 5000 Da) and when the PEG-lipid acyl chain length matched the acyl chain length of the liposomal core phospholipid. Simultaneously to the PEGylation extent, self-diffusion (1)H NMR provides information about the size of micelles and liposomes. The size of the micellar aggregates decreased as the PEG-lipid content was increased while the liposome size remained invariant.
Greene GW, Zappone B, Zhao B, Söderman O, Topgaard D, Rata G, Israelachvili JN. Changes in pore morphology and fluid transport in compressed articular cartilage and the implications for joint lubrication. Biomaterials. 2008;29(33):4455–62. doi:10.1016/j.biomaterials.2008.07.046
Cartilage sections were cut from the middle zone of pig knee articular cartilage and attached to substrates in two different kinds of newly designed ’pressure cells’, one for fluorescence the other for NMR measurements. The fluorescence cell was filled with buffer solution containing fluorescently marked 70 kDa dextran which was allowed to diffuse into the cartilage pores. A second glass surface was then pressed down onto the thin cartilage sample under different loads (pressures), and the resulting compression (strain) and change in pore volume were measured as a function of time, simultaneously with measurements of the lateral diffusion and flow pattern of the dextran molecules using Fluorescence Recovery After Photobleaching (FRAP). Complementary experiments were made on the normal diffusion coefficients of pure electrolyte solutions (no dextran) in thicker cartilage sections with pulse-gradient NMR using a new pressure cell suitable for such measurements. Taken together our results show that the highly anisotropic structure of cartilage has a strong effect on the way fluid diffuses laterally and normally at different stages of compression. Our results also show how geometric constraints on a cartilage network and trapped high MW polymer such as HA during normal compressions are likely to affect both the normal and the lateral mobilities of polyelectrolytes and water.
McCarley RW, Nakamura M, Shenton ME, Salisbury DF. Combining ERP and structural MRI information in first episode schizophrenia and bipolar disorder. Clin EEG Neurosci. 2008;39(2):57–60.
The electrical activity in the electroencephalogram (EEG) and the event-related potentials extracted from the EEG provide the greatest temporal resolution for examining brain function. When coupled with the high spatial resolution of structural magnetic resonance imaging (sMRI), the combined techniques provide a powerful tool for neuroscience in the examination of brain abnormalities in major psychiatric illnesses. Over the last 20 years, our work has examined brain structure and function in schizophrenia. Both EEG and MRI measures have indicated profound abnormalities in schizophrenia within the temporal lobe, particularly marked over the left hemisphere. Our studies of patients first hospitalized due to psychosis revealed the early course of the disease to be characterized by progressive impairment and cortical gray matter reduction, most intense near the time of first hospitalization. Knowledge of those locations and brain signals affected early should help understand the basic physiological defect underlying this progression, with potential implications for new therapeutic interventions.
Koo M-S, Levitt JJ, Salisbury DF, Nakamura M, Shenton ME, McCarley RW. A cross-sectional and longitudinal magnetic resonance imaging study of cingulate gyrus gray matter volume abnormalities in first-episode schizophrenia and first-episode affective psychosis. Arch Gen Psychiatry. 2008;65(7):746–60. doi:10.1001/archpsyc.65.7.746
CONTEXT: Previous magnetic resonance imaging (MRI) findings have demonstrated psychopathological symptom-related smaller gray matter volumes in various cingulate gyrus subregions in schizophrenia and bipolar disorder. However, it is unclear whether these gray matter abnormalities show a subregional specificity to either disorder and whether they show postonset progression. OBJECTIVE: To determine whether there are initial and progressive gray matter volume deficits in cingulate gyrus subregions in patients with first-episode schizophrenia (FESZ) and patients with first-episode affective psychosis (FEAFF, mainly manic) and their specificity to FESZ or FEAFF. DESIGN: A naturalistic cross-sectional study at first hospitalization for psychosis and a longitudinal follow-up approximately 1(1/2) years later. SETTING AND PARTICIPANTS: Patients were from a private psychiatric hospital. Thirty-nine patients with FESZ and 41 with FEAFF at first hospitalization for psychosis and 40 healthy control subjects (HCs) recruited from the community underwent high-spatial-resolution MRI, with follow-up scans in 17 FESZ patients, 18 FEAFF patients, and 18 HCs. Individual subjects were matched for age, sex, parental socioeconomic status, and handedness. MAIN OUTCOME MEASURES: Cingulate gyrus gray matter volumes in 3 anterior subregions (subgenual, affective, and cognitive) and 1 posterior subregion, and whether there was a paracingulate sulcus.
BACKGROUND: In cases of slipped capital femoral epiphyses (SCFE) findings on plain radiographs help to determine the further necessary course of action. In severe cases possible surgical procedures are commonly indicated and planned using angular measurements on plain radiographs to describe the extent and direction of the slip. The aim of this study was to quantify the amount of angular errors deriving from this method. METHODS: Data and imaging of 23 consecutive patients with SCFE (31 affected and 15 unaffected femora) were included in this study. We determined shaft-neck/shaft-physis angles on antero-posterior and torsional angles on lateral radiographs in a clinical setting. As a reference we enabled similar angular measurements on CT-based three-dimensional computer models of the same femora bearing no projectional errors and malpositioning problems. RESULTS: In average, shaft-neck- and shaft-physis-angles were overestimated (6.5 degrees and 10.1 degrees ) on plain radiographs and neck torsion underestimated (-15.7 degrees ). In general the variability was high, especially for neck and physeal torsional measurements with standard deviations of +/-11.8 degrees and +/-16.7 degrees . Three out of four torsional measurements on affected femora were outside a +/-10 degrees window of error, about every third outside a +/-20 degrees window. CONCLUSION: Our results suggest to be careful when using plain radiographs as a source to determine the slippage extent in SCFE. Before using a plain radiograph to reject or indicate and plan a correction osteotomy in an individual case of SCFE the surgeon should reassure that radiographic method and patient positioning provide a reproducible and accurate depiction of the femoral geometry. LEVEL OF EVIDENCE: Level II; 23 consecutive patients with SCFE in the senior authors practice; evaluation of the reliability of angular measurements on plain radiographs; CT based 3D computer models of the same femora as a reference.
Spencer KM, Niznikiewicz MA, Shenton ME, McCarley RW. Sensory-evoked gamma oscillations in chronic schizophrenia. Biol Psychiatry. 2008;63(8):744–7. doi:10.1016/j.biopsych.2007.10.017
BACKGROUND: The early visual-evoked gamma oscillation (VGO) elicited by Gestalt stimuli is reduced in schizophrenia patients compared with healthy individuals, but it is unknown whether this effect is specific to these particular stimuli and task. In contrast, the early auditory-evoked gamma oscillation (AGO) was reported to be unaffected in a sample of unmedicated, mostly first-episode schizophrenics, but it is unknown whether this oscillation is abnormal in chronic, medicated patients. We investigated these issues by examining the VGO and AGO in chronic schizophrenic (SZ) and matched healthy control (HC) subjects. METHODS: Subjects (21 HC, 23 SZ) performed visual and auditory oddball tasks. Visual stimuli were letters, and auditory stimuli were simple tones. Event-related spectral measures (phase locking factor and evoked power) were computed on Morlet wavelet-transformed single epochs from the standard trials. RESULTS: VGO phase locking at occipital electrodes was reduced in SZ compared with HC. In contrast, AGO phase locking and evoked power did not differ between groups. CONCLUSIONS: The VGO deficit may be a general phenomenon in schizophrenia, whereas the AGO evoked by simple tone stimuli does not appear to be abnormal in chronic, medicated schizophrenia patients.
Dickey CC, Mórocz IA, Niznikiewicz MA, Voglmaier M, Toner S, Khan U, Dreusicke M, Yoo S-S, Shenton ME, McCarley RW. Auditory processing abnormalities in schizotypal personality disorder: an fMRI experiment using tones of deviant pitch and duration. Schizophr Res. 2008;103(1-3):26–39. doi:10.1016/j.schres.2008.04.041
BACKGROUND: One of the cardinal features of schizotypal personality disorder (SPD) is language abnormalities. The focus of this study was to determine whether or not there are also processing abnormalities of pure tones differing in pitch and duration in SPD. METHODS: Thirteen neuroleptic-na ıve male subjects met full criteria for SPD and were group-matched on age and parental socio-economic status to 13 comparison subjects. Verbal learning was measured with the California Verbal Learning Test. Heschl’s gyrus volumes were measured using structural MRI. Whole-brain fMRI activation patterns in an auditory task of listening to tones including pitch and duration deviants were compared between SPD and control subjects. In a second and separate ROI analysis we found that peak activation in superior temporal gyrus (STG), Brodmann Areas 41 and 42, was correlated with verbal learning and clinical measures derived from the SCID-II interview. RESULTS: In the region of the STG, SPD subjects demonstrated more activation to pitch deviants bilaterally (p
Saveyn P, Cocquyt E, Sinnaeve D, Martins J e C, Topgaard D, Van der Meeren P. NMR study of the sorption behavior of benzyl alcohol derivatives into sonicated and extruded dioctadecyldimethylammonium chloride (DODAC) dispersions: the relevance of membrane fluidity. Langmuir. 2008;24(7):3082–9. doi:10.1021/la703285b
The sorption behavior of three benzyl alcohol derivatives with different hydrophobicities into sonicated and extruded DODAC dispersions has been studied using NMR spectroscopy and NMR diffusometry. We show that there is an increased sorption into a sonicated dispersion below the phase-transition temperature (T(m)) as compared to an extruded dispersion. This may be explained by the incomplete lipid chain freezing of charged lipids as a result of the sonication process. Around T(m), a sorption maximum is found that is attributed to the high bilayer disorder under this condition. In addition, a sorption increase and a fluidizing effect at increasing benzyl alcohol derivative concentrations are observed that provide additional evidence for the relevance of the bilayer fluidity on the sorption of hydrophobic components.
Nakamura M, Nestor PG, Levitt JJ, Cohen AS, Kawashima T, Shenton ME, McCarley RW. Orbitofrontal volume deficit in schizophrenia and thought disorder. Brain. 2008;131(Pt 1):180–95. doi:10.1093/brain/awm265
Orbitofrontal Cortex (OFC) structural abnormality in schizophrenia has not been well characterized, probably due to marked anatomical variability and lack of consistent definitions. We previously reported OFC sulcogyral pattern alteration and its associations with social disturbance in schizophrenia, but OFC volume associations with psychopathology and cognition have not been investigated. We compared chronically treated schizophrenia patients with healthy control (HC) subjects, using a novel, reliable parcellation of OFC subregions and their association with cognition, especially the Iowa Gambling Task (IGT), and with schizophrenic psychopathology including thought disorder. Twenty-four patients with schizophrenia and 25 age-matched HC subjects underwent MRI. OFC Regions of Interest (ROI) were manually delineated according to anatomical boundaries: Gyrus Rectus (GR); Middle Orbital Gyrus (MiOG); and Lateral Orbital Gyrus (LOG). The OFC sulcogyral pattern was also classified. Additionally, MiOG probability maps were created and compared between groups in a voxel-wise manner. Both groups underwent cognitive evaluations using the IGT, Wisconsin Card Sorting Test, and Trail Making Test (TMT). An 11% bilaterally smaller MiOG volume was observed in schizophrenia, compared with HC (F(1,47) = 17.4, P = 0.0001). GR and LOG did not differ, although GR showed a rightward asymmetry in both groups (F(1,47) = 19.2, P 0.0001). The smaller MiOG volume was independent of the OFC sulcogyral pattern, which differed in schizophrenia and HC (chi2 = 12.49, P = 0.002). A comparison of MiOG probability maps suggested that the anterior heteromodal region was more affected in the schizophrenia group than the posterior paralimbic region. In the schizophrenia group, a smaller left MiOG was strongly associated with worse ’positive formal thought disorder’ (r = -0.638, P = 0.001), and a smaller right MiOG with a longer duration of the illness (r = -0.618, P = 0.002). While schizophrenics showed poorer performance than HC in the IGT, performance was not correlated with OFC volume. However, within the HC group, the larger the right hemisphere MiOG volume, the better the performance in the IGT (r = 0.541, P = 0.005), and the larger the left hemisphere volume, the faster the switching attention performance for the TMT, Trails B (r = -0.608, P = 0.003). The present study, applying a new anatomical parcellation method, demonstrated a subregion-specific OFC grey matter volume deficit in patients with schizophrenia, which was independent of OFC sulcogyral pattern. This volume deficit was associated with a longer duration of illness and greater formal thought disorder. In HC the finding of a quantitative association between OFC volume and IGT performance constitutes, to our knowledge, the first report of this association.