Inhibitory effects of oleic and docosahexaenoic acids on lung metastasis by colon-carcinoma-26 cells are associated with reduced matrix metalloproteinase-2 and -9 activities

Structural and functional neuroimaging techniques have consistently demonstrated that abnormal lateralization of temporal lobes may be important in identifying the pathophysiologic processes in schizophrenia. The exact nature of these reported abnormalities has not been consistent. METHODS: We examined temporal lobe perfusion using HMPAO-SPECT in 22 individuals with schizophrenia in an effort to establish whether temporal lobe perfusion asymmetry is seen in these individuals, as compared to a group of 22 age- and sex-matched controls. RESULTS: We found that the asymmetry index, a measure of perfusion differences between two homologous compared areas, was lower (more negative) in schizophrenic individuals. The asymmetry indices of patients considered with the results from globally corrected ROI means indicated that the left temporal lobes of individuals with schizophrenia were significantly hypoperfused when compared to controls. This finding does not appear to be caused by medication effects, demographic variables, handedness, imaging artifacts or analysis techniques. CONCLUSION: In our sample, patients with schizophrenia appear to have significant left hypoperfusion relative to right of their temporal lobes. Abnormal lateralization of temporal lobe blood flow may have important clinical implications by assisting with diagnosis and appropriate treatment for individuals with schizophrenia.     

Application of cognitive scales to medical records of schizophrenia inpatients

Studies with proton magnetic resonance spectroscopy (MRS) have reported abnormalities in N-acetyl-aspartate (NAA), amino acids (AA) and choline (Cho) to creatine (Cr) ratios associated with schizophrenia. We report data on the three ratios in a sample of 18 neuroleptic naive patients with first-episode schizophrenia (eight studied in the dorsolateral prefrontal and 10 in the midtemporal lobe) and 24 healthy controls (14 studied in prefrontal and 10 in midtemporal lobes). Frontal lobe proton spectra were acquired with the stimulated-echo acquisition mode (STEAM) pulse sequence (echo time 21 ms, repetition time 2 s). Temporal lobe proton spectra were acquired with the point-resolved spectroscopy (PRESS) pulse sequence (echo time 16-21 ms, repetition time 2 s). Upon comparison with normal controls, NAA/Cr ratios were reduced in patients both for the frontal and the temporal lobe. By contrast, Cho/Cr ratios were slightly elevated in frontal and reduced in temporal lobes; whereas, AA/Cr ratios were normal in frontal and markedly increased in the temporal lobe. The reduced NAA/Cr ratios suggest lower neuronal viability in patients and is consistent with findings of reduced brain volume in both frontal and temporal regions.     

Functionality and connectivity analysis by magnetic resonance imaging

Magnetic resonance (MR is a remarkably versatile technology applicable to various aspects of medical science. Currently, there are three categories of MR techniques available for probing human brain function in detail. The first category comprises the most widely utilized techniques which make use of the metabolic effects of brain activation, represented by BOLD (blood oxygenation level dependent) functional magnetic resonance imaging (fMRI). The second category of techniques deals with apparent diffusion tensor probing the axonal connectivity and is represented by three dimensional anisotropy contrast (3DAC) axonography. The third category of techniques is a biological application of classical nuclear magnetic resonance (NMR) spectroscopy capable of providing biochemical information in vivo and is represented by spectroscopic imaging (SI). As techniques directly applicable to clinical medicine, BOLD fMRI and 3DAC axonography possess the highest potential.     

Research and treatment strategies in first-episode psychoses. The Pittsburgh experience

BACKGROUND: Studies of first-episode patients allow investigation of the biological basis of psychotic disorders without the potential confounds of prior treatment and illness chronicity. Prospective studies of this population can clarify the impact of illness course and treatment on neurobiology. METHOD: We summarise preliminary findings from our ongoing magnetic resonance imaging and spectroscopy studies of first-episode schizophrenia patients being conducted prospectively from index evaluations through a period of two years; during this period, patients were treated with either a conventional antipsychotic such as haloperidol, or the atypical risperidone. RESULTS: Baseline neurobiological evaluations in first-episode schizophrenia patients have revealed evidence for structural and functional brain abnormalities consistent with a neurodevelopmental model of this illness. Our preliminary data support the value of risperidone as an antipsychotic drug of first choice among patients with early schizophrenic illness. CONCLUSIONS: Focused studies of first-episode patients have the potential to unravel pathophysiology of schizophrenic illness. Such knowledge is critical for more effective early detection, intervention and even prevention of this enigmatic disorder.     

Psychopharmacology--in vivo neurochemistry and pharmacology

Positron emission tomography (PET) and single photon emission computerized tomography (SPECT) brain imaging techniques are powerful tools for the investigation of human neurochemistry and psychopharmacology. These versatile in vivo methods can be used to measure brain receptor populations in psychiatric illness, to determine receptor occupancy and tissue pharmacokinetics of psychotropic drugs and to examine the functional effects of drug-induced neurotransmitter manipulation. This chapter reviews recent innovative basic and clinical studies, of relevance to psychiatry, and discusses methodological developments that extend the use of these techniques.     

Does intravenous administration of GABA(A) receptor antagonists induce both descending antinociception and touch-evoked allodynia?

Recent magnetic resonance imaging (MRI) and magnetic resonance spectroscopic (MRS) techniques have focused the attention of the multiple sclerosis (MS) research community on reanalysis of classic pathological approaches that have suggested significant axonal injury in this demyelinating disease. There now is abundant evidence from animal work that substantial "innocent bystander" damage to axons can occur with central nervous system (CNS) inflammation. Given the close interactions between axons and glia, it is no surprise that glial damage leads to secondary axonal changes. MRI, MRS, and MRS imaging studies have emphasized that axonal loss or damage in MS can be both substantial and early. The dynamic observations that are allowed by these noninvasive measures of pathology have demonstrated direct correlations between these axonal changes and disability, making a compelling case for increased emphasis on finding treatments of MS that may limit damage to CNS axons or salvage injured axons.     

The effect of SDS, sodium dodecyl sulfate, on the metabolism and swimming capacity of Cyprinus carpio

Currently, diagnoses of attention deficit hyperactivity disorder (ADHD) and hyperkinetic disorder (HKD) are made on the basis of phenomenology, but information is accumulating from the neurosciences about the biological bases of these disorders. Recent studies addressing the neuropsychology, neuroanatomy, neurochemistry, and molecular biology of ADHD/HKD document abnormalities in well-defined neuroanatomical networks and neurochemical pathways. Magnetic resonance imaging (MRI) studies have shown that some regions of the frontal lobes (anterior superior and inferior) and basal ganglia (caudate nucleus and globus pallidus) are about 10% smaller in ADHD groups than in control groups of children, and molecular genetic studies have shown that diagnosis of ADHD is associated with polymorphisms in some dopamine genes (the dopamine D4 receptor gene and the dopamine transporter gene).     

Magnetic resonance spectroscopy: use in monitoring MELAS treatment

BACKGROUND: Sodium dichloroacetate has been used to treat patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Magnetic resonance spectroscopy (MRS) has been used to assess cerebral metabolism in MELAS, but to our knowledge, the findings of serial MRS studies performed after therapeutic intervention of strokelike episodes have not been reported. METHODS: Proton MRS was serially used to measure brain metabolites in strokelike regions and in clinically uninvolved brain regions in a patient with MELAS. PATIENT: A patient with MELAS and a strokelike episode clinically improved after treatment with sodium dichloroacetate. An elevated lactate-creatine ratio in the "stroke" region decreased on MRS studies after treatment. After a second episode, the lactate-creatine ratio increased from baseline in a region of the brain that was normal on magnetic resonance imaging scans. CONCLUSIONS: To our knowledge, this is the first study to assess the response to treatment of a MELAS strokelike episode and the first to show an increase in the lactate-creatine ratio in a brain region that was associated with a clinical abnormality, even though it appeared normal on magnetic resonance imaging. We conclude that MRS may help to monitor therapeutic efficacy in mitochondrial encephalomyopathies.     

Solid-state NMR for the study of membrane systems: the use of anisotropic interactions

The use of solid-state nuclear magnetic resonance (NMR) as a tool to determine the structure of membrane molecules is reviewed with a particular emphasis on techniques that provide information on orientation or order. Experiments reported here have been performed in membranes, rather than in micelles or organic solvents. Several ways to prepare and handle the samples are discussed, like sample orientation and magic-angle spinning (MAS). Results concerning lipids, membrane peptides and proteins are included, as well as a discussion regarding the potential of such methods and their pitfalls.     

Magnetic resonance spectroscopy in psychiatry: basic principles and applications

In vivo magnetic resonance spectroscopy (MRS) is a safe and non-invasive tool which can be used to study aspects of brain chemistry and metabolism. Although a relatively recent technique in the field of psychiatric research, it has already been used in the study of anxiety and affective disorders, dementia, schizophrenia, and neurodevelopmental disorders. This review outlines the basic principles of MRS and summarises the research findings in psychiatric disorders. Although mostly preliminary, these findings highlight the capacity of MRS to detect subtle neurobiological abnormalities in mental disorders. They also suggest a future role for MRS in differential diagnosis and monitoring illness progression. Initial MRS studies have also focused on the metabolic effects of psychiatric treatments and could provide information about their relationship to clinical variables.     

Deficits in gray matter volume are present in schizophrenia but not bipolar disorder

Studies using magnetic resonance (MR) imaging have provided strong evidence that patients with schizophrenia as a group have structural brain abnormalities, including enlarged ventricles and sulci as well as smaller cortical gray matter volumes. This study was undertaken to investigate whether the brain abnormalities found in schizophrenia could be distinguished from those seen in bipolar disorder. The MR scans of 23 patients with schizophrenia were compared to those of 17 healthy community volunteers and 14 patients with bipolar disorder. Images were processed using computer-based image processing techniques to generate quantitative measures of cerebrospinal fluid (CSF), gray matter and white matter volumes. Compared to the community volunteers, the schizophrenia group had larger total CSF volumes while the bipolar group had larger ventricles. Smaller cortical gray matter volumes were found in the schizophrenia group, but not in the bipolar group. The schizophrenia group had regional deficits in gray matter volumes in comparison with both the community volunteers and the bipolar group. These findings suggest that the brain tissue abnormalities found in schizophrenia and bipolar disorder may be distinguishable using MR imaging.     

Anatomy of the upper extremity muscle compartments

Schizophrenia, a devastating disease characterized by a combination of various types of disturbed behaviors, thoughts, and feelings, may likewise be heterogeneous in etiology. Recent advances in neuroscience and psychopharmacology have suggested a wide array of competing mechanisms that may be involved in schizophrenia, including but not limited to deficits in one or more neurotransmitters and second messenger systems (e.g., dopamine, serotonin, gamma-aminobutyric acid, glutamate, and noradrenaline), neurodevelopmental defects in brain circuitry, and viral infection. Psychiatric genetic studies indicate that schizophrenia is a disorder with multifactorial inheritance. Since cerebral metabolic activity reflects regional brain work for all neurotransmitter systems, imaging metabolism directly with fluorodeoxyglucose and indirectly with blood flow and hemoglobin oxygen saturation can provide information about the functional neuroanatomy of a deficit in individual patients and allow patients to be grouped into more homogeneous subgroups for intensive study. This review summarizes metabolic imaging studies in schizophrenia over the past decade.     

Decreased left frontal lobe N-acetylaspartate in schizophrenia

OBJECTIVE: The authors measured N-acetylaspartate (a putative neuronal marker), using in vivo proton magnetic resonance spectroscopic imaging (1H-MRSI), in the frontal lobes of schizophrenic patients and normal subjects. METHOD: Frontal lobe 1H-MRSI was performed bilaterally on 24 medicated schizophrenic patients and 15 healthy comparison subjects. Levels of N-acetylaspartate, creatine, and choline were determined. RESULTS: Relative to the comparison group, the patients with schizophrenia demonstrated significantly lower levels of N-acetylaspartate in the left frontal lobe. There was no association between level of N-acetylaspartate and duration of illness or medication dosage. No differences between groups or lateralized asymmetries in choline or creatine were noted. CONCLUSIONS: This preliminary study provides support for decreased N-acetylaspartate in the left frontal lobe in schizophrenia and neuronal dysfunction in this brain region.     

Regionally specific pattern of neurochemical pathology in schizophrenia as assessed by multislice proton magnetic resonance spectroscopic imaging

OBJECTIVE: Several single-voxel proton magnetic resonance spectroscopy (1H-MRS) studies of patients with schizophrenia have found evidence of reductions of N-acetyl-aspartate (NAA) concentrations in the temporal lobes. Multislice proton magnetic resonance spectroscopy imaging (1H-MRSI) permits simultaneous acquisition and mapping of NAA, choline-containing compounds (CHO), and creatine/phosphocreatine (CRE) signal intensities from multiple whole brain slices consisting of 1.4-ml single-volume elements. We have used 1H-MRSI to assess the regional specificity of previously reported changes of metabolite signal intensities in schizophrenia. Hippocampal volume was also measured to test the relationship between 1H-MRSI findings and tissue volume in this region. METHOD: Ratios of areas under the metabolite peaks of the proton spectra were determined (i.e., NAA/CRE, NAA/CHO, CHO/CRE) for multiple cortical and subcortical regions in 10 inpatients with schizophrenia. RESULTS: Patients showed significant reductions of NAA/CRE and NAA/CHO bilaterally in the hippocampal region and in the dorsolateral prefrontal cortex. There were no significant changes in CHO/CRE or in NAA ratios in any other area sampled. No significant correlation was found between metabolite ratios in the hippocampal region and its volume. CONCLUSIONS: NAA-relative signal intensity reductions in schizophrenia appear to be remarkably localized, involving primarily the hippocampal region and the dorsolateral prefrontal cortex, two regions implicated prominently in the pathophysiology of this disorder.     

Human fibroblasts in culture metabolize differently exogenous G(M3) ganglioside species containing C18 and C20 sphingosine

Applications of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) in studies of body composition are discussed. MRI is an accurate method for volume quantification of lean and adipose tissue in the human body, while MRS is used to study in vivo metabolism of soft tissues. In particular, combination of MRI and phosphorus (31P) MRS, used to asses muscle energy metabolism, may be of great importance in body composition studies. Examples of use of MRI and 31P MRS in studying the effect of caloric restriction on body composition and skeletal muscle metabolism are given.     

Brain proton magnetic resonance spectroscopy. Indications for diagnosis and follow-up of HIV-related encephalopathy in the adult

NONINVASIVE EXPLORATION: Proton localized magnetic resonance spectroscopy (MRS) is a noninvasive human neurochemistry method based on the magnetic resonance phenomenon. ADVANTAGES: This exploration of brain metabolism, performed without any injection, detects neuronal, glial, and membrane markers, and can be performed after an MRI examination without moving the patient. INDICATIONS: In vivo brain MRS plays a major role (i) in early diagnosis of HIV-related encephalopathy, (ii) in differential diagnosis of HIV-related encephalopathy versus psychiatric symptoms or occurring in AIDS patients, (iii) in differential diagnosis of HIV-related encephalopathy versus other brain lesions related to AIDS, and (iv) in the follow-up of patient response to therapy. In these indications, MRS is frequently more reliable than neuropsychologic testing and more sensitive than MRI.     

Oxygen imaging in perfused hearts by dynamic nuclear polarization

The feasibility of localized oximetry by dynamic nuclear polarization (DNP) imaging is demonstrated on perfused sheep hearts. DNPI is a magnetic, double resonance technique, in which the electron paramagnetic resonance (EPR) of a free radical dissolved in a perfusion medium is saturated, while the nuclear magnetic resonance (NMR) of water protons is used to perform conventional NMR imaging. The presence of oxygen reduces the enhancement of the NMR signal induced by DNP. The oxygen content of sheep heart tissues was detected by the subtraction of the DNP image of the heart, perfused with a nitrogen-equilibrated solution, from an image obtained when the heart was perfused with an oxygen-equilibrated solution. This result was obtained with extreme oxygen partial pressure, and the discussion presents physical and chemical means for improving the DNP imaging method. Physical means include field cycling, electron paramagnetic rotary saturation, and the use of a 180 degrees NMR pulse before EPR irradiation. The chemical means discussed are deuterium substitution in nitroxides and the potential use of solid, free radical probes. It is suggested to use the perfused heart model for comparing the numerous methods available to measure the oxygen content of tissues.     

Source monitoring 15 years later: What have we learned from fMRI about the neural mechanisms of source memory?

Focusing primarily on functional magnetic resonance imaging (fMRI), this article reviews evidence regarding the roles of subregions of the medial temporal lobes, prefrontal cortex, posterior representational areas, and parietal cortex in source memory. In addition to evidence from standard episodic memory tasks assessing accuracy for neutral information, the article considers studies assessing the qualitative characteristics of memories, the encoding and remembering of emotional information, and false memories, as well as evidence from populations that show disrupted source memory (older adults, individuals with depression, posttraumatic stress disorder, or schizophrenia). Although there is still substantial work to be done, fMRI is advancing understanding of source memory and highlighting unresolved issues. A continued 2-way interaction between cognitive theory, as illustrated by the source monitoring framework (M. K. Johnson, S. Hashtroudi, & D. S. Lindsay, 1993), and evidence from cognitive neuroimaging studies should clarify conceptualization of cognitive processes (e.g., feature binding, retrieval, monitoring), prior knowledge (e.g., semantics, schemas), and specific features (e.g., perceptual and emotional information) and of how they combine to create true and false memories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Oculomotor abnormalities in schizophrenia: a critical review

Oculomotor abnormalities, particularly in smooth pursuit tracking, are one of the most widely investigated biological markers of schizophrenia. However, despite the wealth of published data, important questions concerning the exact nature of these abnormalities remain unanswered. Many of the studies use unreliable methodology, and few attempts have been made to interpret the observed oculomotor dysfunction in terms of current understanding of eye movement physiology. Also, the potential effects of antipsychotic medication have been poorly addressed. Recent research, using more reliable measurement techniques and novel saccadic paradigms are producing important results and may provide a more productive framework for future studies of oculomotor abnormalities in schizophrenia.