bluuebunny/crossref_metadata_2025 huggingface dataset:
Urinary Excretion of the Nitrotyrosine Metabolite 3-Nitro-4-Hydroxyphenylacetic Acid in Preterm and Term Infants
Authors: Hoehn Thomas , Janssen Sylvia , Mani Ali R. , Brauers Gernot , Moore Kevin P. , Schadewaldt Peter , Mayatepek Ertan
Published: August 2007

Background: Newborn infants are exposed to various sources of oxidative and/or nitrative stress, which refers to either oxidation and/or nitration of endogenous proteins including loss of their original function. Nitrative stress is predominantly caused following synthesis of peroxynitrite. Particularly preterm infants with immature defense mechanisms against free radical injury appear at risk. Objective:To test the feasibility of quantifying the degradation products of the peroxynitrite marker nitrotyrosine [3-nitro-4-hydroxyphenylacetic acid (NHPA) and para-hydroxyphenylacetic acid (PHPA)] in neonatal urine samples. Methods:NHPA and PHPA were determined by gas chromatography/mass spectroscopy in urinary samples of preterm and term infants (mean gestational age = 28.4 and 39.6 weeks, respectively). Results: The urinary NHPA levels were lower in preterm infants in comparison with term infants. When the NHPA levels were adjusted to the urinary PHPA levels, no differences were found between the two groups. Conclusions: Nitrotyrosine can be quantified in urinary samples of even the most immature infants. Nitration of endogenous PHPA in the gastrointestinal tract of term infants may have masked potentially higher levels of NHPA in preterm infants.
A Score Method for Comparison of Partial Genomic Regions in Their Representatives of Full-Length Genome of Hepatitis E Virus for Genotyping
Authors: Xun Pengcheng , Chen Feng , Dong Chen , Qian Guohua , Lai Dejian , Meng Jihong
Published: August 2007

In this article, a statistical score method for comparison of partial genomic regions in their representatives of full-length genome of hepatitis E virus (HEV) for genotyping was developed. The critical values of the statistics for hypothesis testing were generated through Monte Carlo simulations. It was found that fragment III might be a statistically representative region for the whole genome of HEV for genotyping. Based on both the full-length sequence and fragment III, the same four genotypes were identified by the subsequent phylogenetic analysis, and similar ranges of mean nucleotide difference were also observed to differentiate HEV sequences at the three levels genotype, subtype and isolate, which further verified the statistical results. It may be concluded from this study that the score method is effective for comparing partial genomic regions with full-length genome of HEV strains for genotyping.
New Aspect of Renal Phosphate Reabsorption: The Type IIc Sodium-Dependent Phosphate Transporter
Authors: Miyamoto Ken-ichi , Ito Mikiko , Tatsumi Sawako , Kuwahata Masashi , Segawa Hiroko
Published: August 2007

Abnormalities of the inorganic phosphate (Pi) reabsorption in the kidney result in various metabolic disorders. Na+-dependent Pi (Na/Pi) transporters in the brush border membrane of proximal tubular cells mediate the rate-limiting step in the overall Pi-reabsorptive process. Type IIa and type IIc Na/Pi cotransporters are expressed in the apical membrane of proximal tubular cells and mediate Na/Pi cotransport; the extent of Pi reabsorption in the proximal tubules is determined largely by the abundance of the type IIa Na/Pi cotransporter. However, several studies suggest that the type IIc cotransporter in Pi reabsorption may also play a role in this process. For example, mutation of the type IIc Na/Pi cotransporter gene results in hereditary hypophosphatemic rickets with hypercalciuria, suggesting that the type IIc transporter plays an important role in renal Pi reabsorption in humans and may be a key determinant of the plasma Pi concentration. The type IIc Na/Pi transporter is regulated by parathyroid hormone, dietary Pi, and fibroblast growth factor 23, and studies suggest a differential regulation of the IIa and IIc transporters. Indeed, differences in temporal and/or spatial expression of the type IIa and type IIc Na/Pi transporters may be required for normal phosphate homeostasis and bone development. This review will briefly summarize the regulation of renal Pi transporters in various Pi-wasting disorders and highlight the role of a relatively new member of the Na/Pi cotransporter family: the type IIc Na/Pi transporter/SLC34A3.
Internalization of Sex Hormone-Binding Globulin into Neurons and Brain Cells in vitro and in vivo
Authors: Caldwell J.D. , Shapiro R.A. , Jirikowski G.F. , Suleman F.
Published: August 2007

Background: Sex hormone-binding globulin (SHBG) is a 94-kDa homodimer that binds steroids and is made in the hypothalamus. We have demonstrated that infusions of SHBG into the hypothalami of rats increase their female sexual receptivity except when SHBG is coupled to dihydrotestosterone (DHT) suggesting that SHBG has an active function in behavioral neuroendocrinology. Methods: This study examines the possibility that SHBG is internalized by neuronal and/or non-neuronal brain cells as one possible mode of action using in vitro and in vivo techniques. Results: First, analysis of the uptake of radiolabeled SHBG (125I-SHBG) found 125I-SHBG uptake in HT22 hippocampal cells stably transfected with cDNA for ERβ (HT22-ERβ). The addition of DHT to 125I-SHBG significantly inhibited 125I-SHBG uptake in HT22-ERβ cells but not in HT22-ERα or HT22 wild-type cells. SHBG internalization was specific as it did not occur in either the human neuroblastoma cell line SK-N-SH or the glioma cell line C6. Second, SHBG was labeled with a fluor (Alexa-555TM), and infused into the lateral cerebroventricles of ovariectomized rats. Optimal SHBG uptake was seen 10 min after these infusions. SHBG uptake was seen in specific parts of the choroid plexus and periventricular cells as well as into cells in the paraventricular nucleus, the medial forebrain bundle, and the habenula. Conclusions: These studies suggest that SHBG is internalized by brain cells, which may be affected by the presence of ERβ. The gonadal steroids have numerous effects in brain and the discovery that the steroid-binding protein SHBG is taken up into neurons and brain cells may demand a change in thinking about how steroids are delivered to brain cells to affect neurophysiology.
Cerebral Cholinergic Activity Is Related to the Incidence of Visual Hallucinations in Senile Dementia of Lewy Body Type
Authors: Perry Elaine K. , Kerwin Janet , Perry Robert H. , Irving Dorothy , Blessed Garry , Fairbairn Andrew
Published: August 2007

Senile dementia of Lewy body type is characterized clinically by presenting symptoms such as acute/ subacute fluctuating confusion and in the majority also visual hallucinations, and neuropathologically by the presence of Lewy bodies especially in archicortical areas. Progressive dementia develops in the course of the disease which shares with Alzheimer''s disease a cortical cholinergic deficit, evident at autopsy. In two of four brain areas examined, parietal and temporal cortex, choline acetyltransferase activities were significantly lower in patients with, compared to those without, hallucinations (20% and 50% of the normal, respectively). These new findings suggest cholinergic mechanisms are involved in hallucinatory experiences and that this clinical feature may be diagnostic of severely deranged cholinergic activity in dementia.
Temporal-Parietal Hypoperfusion with Single-Photon Emission Computerized Tomography in Conditions Other than Alzheimer's Disease
Authors: Miller Bruce L. , Mena Ismael , Daly James , Giombetti Robert J. , Goldberg Mark A. , Lesser Ira , Garrett Karen , Villanueva-Meyer Javier , Liu Ching-Kuan
Published: August 2007

Single-photon emission computerized tomography demonstrates temporal-parietal (TP) hypoperfusion in many patients with Alzheimer''s disease (AD). However, the specificity of these changes has not yet been determined. We have found TP hypoperfusion in five groups of patients including 1 patient with normal aging, 6 with sleep apnea, 1 with posthypoxic dementia, 5 with multi-infarct dementia and 2 with ''pseudo'' TP hypoperfusion with frontal seizures. These findings suggest that the TP cortex may be particularly sensitive to hypoxia and/or hypotension and that hypoperfusion to TP Cortex is not specific to AD.
Galanthamine Hydrobromide in a Long-Term Treatment of Alzheimer's Disease
Authors: Thomsen T. , Bickel U. , Fischer J.P , Kewitz H.
Published: August 2007

We investigated the long-term administration of galanthamine hydrobromide, a cholinesterase inhibitor, in Alzheimer''s disease. The patient was at an advanced stage of the disease and remained unchanged with respect to the results of psychometrical tests. The clinical global impression, however, improved with dosage, and clinical improvement was associated with a remarkable and selective inhibition of acetylcholinesterase activity. Galanthamine was well tolerated without adverse effects or pathological changes in laboratory values, although high doses were given. Intravenous administration of galanthamine to a healthy volunteer revealed that the time course of acetylcholinesterase inhibition and plasma levels of the drug were closely correlated. The pharmacokinetics of galanthamine behaved linearly over the entire dosage range; plasma levels were equal to the concentrations in erythrocytes, and the elimination half-life was even longer than 4.5 h, as described by Westra and co-workers, in anaesthetized patients.
Neurochemical Aspects of Dementia Disorders
Authors: Gottfries C.G.
Published: August 2007

Dementia disorders are syndromes of cognito-emotional impairment which are disabling and longstanding. Subgroups of dementia are idiopathic dementias or primary degenerative dementias, vascular dementias and secondary dementias. Neurochemical investigations of postmortem human brain material have shown multiple changes in the neurotransmitter metabolism in patients with Alzheimer''s disease (AD) and senile dementia of the Alzheimer type (SDAT). The cholinergic system is severely disturbed, but also the serotonin system and the catecholamines are disturbed. Reduced concentrations of neuropeptides have also been reported in AD/SDAT. It is obvious, however, that in brains from Alzheimer-afflicted patients, there are also disturbances in gangliosides and white matter components. At present, it is not possible to single out one of these changes as of special importance for the dementia disorder. The recorded neurochemical changes in brains from patients with AD/SDAT must, at present, be assumed to be secondary phenomena to a more fundamental disturbance, the nature of which we still do not know. Another explanation may be that the group AD/SDAT is a heterogeneous group, including several from an etiopathological point of view different disorders. In vascular dementia, there seem to be subgroups, and the multi-infarct dementia (MID) is only one of these. In a non-MID vascular group, there are general neurochemical disturbances in the form of reduced activity of cholineacetyl transferase and concentrations of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid. Although the neurochemical changes in dementia disorders are looked upon as secondary phenomena, they are of pathogenetic importance. Significant correlations have also been shown between neurotransmitter disturbances and behavioral symptoms. Thus, the neurochemical changes form a basis for formulating treatment strategies.
Impairment of Passive and Active Avoidance Produced by Destruction of the Cholinergic Projection from the Pedunculopontine Nucleus to the Medial Thalamus of the Rat
Authors: Fujimoto Ken-ichi , Yoshida Mitsuo , Ikeguchi Kunihiko , Ogawa Matsuo
Published: August 2007

Areas of pedunculopontine nuclei (PPN) of rats were Iesioned bilaterally by local injection of ibotenic acid. The medial thalamus (MT) where the cholinergic efferent fibers of the PPN terminate was also Iesioned bilaterally by local injection of ethylcholine mustard aziridinium ion. Testing of these Iesioned rats for passive as well as active avoidance behaviors revealed that their avoidance ability was severely impaired. In both PPN- and MT-lesioned rats, the choline acetyltransferase activity decreased significantly in the MT. These findings suggest that the cholinergic PPN-MT projection plays an important role in learning and memory processes.
Regional Cholinergic Differences in the Brain of DBA/2 and C57BL/6 Mice: A Morphological Study during Ontogeny
Authors: Schwab Claudia , Brückner Gerd , Castellano Claudio , Oliverio Alberto , Biesold Dietmar
Published: August 2007

C57BL/6 and DBA/2 mice present a number of behavioral and neurobiological differences and react in opposite ways to cholinergic drugs. A morphological study during ontogony of brain cholinergic organization of these strains was therefore performed by using acetylcholinesterase pharmacohistochemistry and choline acetyltransferase immunohistochemistry. Cross-sectional areas and rostrocaudal measures of selected brain regions were analyzed. C57 mice were characterized by a lower cholinergic density. This deficit was most pronounced in the striatum, the nucleus basalis of Meynert and the nucleus of the diagonal band of Broca. The observed strain differences were shown to be age-related by using mice aged 20–110 postnatal days. The differentially expressed cholinergic deficit in C57 mice may lead to an approach of the degenerative patterns of cholinergic systems in humans.
Evaluation of a Short Mental Test for the Diagnosis of Dementia
Authors: Treves Therese A. , Ragolsky Micha , Gelernter Ilana , Korczyn Amos D.
Published: August 2007

A Short Mental Test (SMT) composed of 26 items was evaluated for screening dementia, taking into account the effect of age and education. The relative contribution of individual items was assessed. The SMT was administered to healthy and demented subjects. Validity was established by a significant relationship between the total score on the SMT (as well as individual items) and the diagnosis established according to DSM-III R criteria. The best diagnostic accuracy (88.4%) was achieved using a cut-off score of 79 correct responses. The question that most successfully diagnosed dementia was subtraction of serial sevens. Subsequent ranking revealed the importance of items requiring abstraction and time orientation. Immediate recall and personal information were least helpful. Age negatively correlated with total scores, but affected recent memory, sentence repetition and proverb interpretation in the higher-schooled population only. Poor schooling evenly lessened general performance.
Co-Occurrence of Affective and Cognitive Symptoms: The Epidemiological Evidence
Authors: Henderson A.S.
Published: August 2007

Affective and cognitive symptoms co-occur considerably above chance in clinical (i.e. treated) samples. By contrast, in population-based surveys, the syndromes of depression and dementia do not occur at the case level more than by chance, but symptoms of each may correlate significantly though never strongly. Epidemiological data from prospective longitudinal studies are now sought, focussed on cases showing both groups of symptoms.
Colocalization of Choline Acetyltransferase and Nerve Growth Factor Receptor in the Rat Basal Forebrain
Authors: Bickel U. , Kewitz H.
Published: August 2007

Nerve growth factor (NGF) is regarded as an important trophic factor for central cholinergic neurons. It only acts on neurons expressing NGF receptors (NGFR). In this study, the extent of colocalization of NGFR and the cholinergic marker, choline acetyltransferase (ChAT), was examined in the basal forebrain of adult rats. Simultaneous labelling for NGFR and ChAT was accomplished by a specific double-immunofluorescence method. An almost complete colocalization of the two antigens was observed in the regions studied. The extent of double-stained neurons ranged from 89.2% (basal nucleus) and 96.9% (horizontal diagonal band) to 99% (vertical diagonal band) and 100% (medial septum). The remaining single labelled cells were immunopositive for ChAT, and only a negligible fraction of them, 0.2% (basal nucleus) and 0.4% (horizontal diagonal band), displayed NGFR immunoreactivity alone. This result emphasizes the specific relationship between NGF and cholinergic neurons in the basal forebrain. These neurons are projecting to hippocampal and cortical targets and are involved in cognition and memory. Investigations evaluating the applicability of NGF treatment to prevent neuronal degeneration may be encouraged by the finding that NGF obviously plays a very specific role in this system.
Serotonergic Modulation of Cholinergic Systems Involved in Learning and Memory in Rats
Authors: Santucci Anthony C. , Kanof Philip D. , Haroutunian Vahram
Published: August 2007

Rats received either N-methyl-D-aspartic-acid-induced bilateral lesions (50 nmol/l µl/side) of a major forebrain cholinergic nucleus (nucleus basalis of Meynert, nbM) or sham operations. After an approximate 1-month recovery period, all subjects were trained and tested on a one-trial passive avoidance task. Thirty minutes prior to training, half of the subjects in each surgical condition were injected with the serotonergic releasing/depleting agent p-chloroamphetamine (2.5 mg/kg), while the other half of subjects received saline injections. Immediately after training, half of the p-chloroamphetamine-injected and saline-injected subjects in each surgical condition were injected with the cholinesterase inhibitor physostigmine (0.06 mg/kg), while the other half were injected with saline. All animals were tested for retention 72 h following training. Disruption of test performance was seen in (1) saline-injected nbM-lesioned animals; (2) sham animals treated with physostigmine alone, and (3) sham and nbM-lesioned animals treated with either p-chloroamphetamine alone, or with p-chloroamphetamine plus physostigmine. Only nbM-lesioned subjects injected with physostigmine alone exhibited enhanced test performance. Lesions of the nbM produced stern depletions in cortical cholinergic enzyme markers (choline acetyltransferase, CAT, and acetylcholinesterase, AChE). Interestingly, p-chloroamphetamine exaggerated both the CAT and AChE depletions in nbM-lesioned animals. These data were interpreted as providing further evidence in support of the view that the cholinergic and serotonergic systems interact at a cognitive and at a neurochemical level. Implications for the therapeutics of Alzheimer''s disease are discussed.
Vascular Dementia
Authors: Loeb Carlo
Published: August 2007

The current assessment of dementia due to vascular causes in terms of terminology, classification, clinical features and diagnostic criteria, neuropathological lesions, risk factors, and possible treatment is reported. The term vascular dementia (VD) covers all syndromes with dementia of vascular origin. The clinical workout may reach a diagnostic sensitivity ranging from 70 to 85%. Verified ischemic lesions associated with dementia include multiple large and small infarctions, multiple lacunes, and, less frequently, watershed infarctions and other vascular diseases. However, the pathological evidence of infarction does not necessarily mean that cerebral vascular lesions are responsible for a state of dementia. The mixed forms (degenerative and vascular dementia) are difficult to assess both from the diagnostic and neuropathological point of view. The etiology of VD is multifactorial.
Monoamine Levels and Functional Indices in Basal Forebrain Nuclei of Aged Rats
Authors: Luine Victoria , Milio Christine
Published: August 2007

Levels of monoamines and indices of monoaminergic function were evaluated in basal forebrain nuclei [vertical diagonal band nucleus (vDB), horizontal diagonal band nucleus (hDB), nucleus basalis (nbM), medial septal nucleus (mS)] and in other brain areas of female young (3-month-old) and aged (24-month-old) Fischer 344 rats. Concentrations of norepinephrine (NE) decreased 25–60% in the vDB, nbM, mS, and locus coeruleus (LC) of aged rats as compared to young rats. Dopamine (DA) and serotonin (5-HT) levels were unchanged in basal forebrain nuclei of aged rats. Using α-methyl-p-tyrosine, an inhibitor of tyrosine hydroxylase, to evaluate catecholaminergic function showed that NE turnover, an index of NE release over time, decreased 66% in the nbM, 40% in the mS, and 83 % in the LC of aged rats. DA turnover decreased approximately 30% in the vDB, mS, and striatum of aged rats. In contrast, the activity of 5-HT endings, assessed by 5-hydroxyindole-acetic acid (5-HIAA) levels and 5-HIAA/5-HT ratios, increased in the hDB and nbM. These results raise the possibility that age-related decreases in catecholaminergic function within basal forebrain nuclei, which are critical for memory function, may contribute to age-related cognitive impairments.
Elevated Activities of Lipases and Lysophospholipase in Alzheimer's Disease
Authors: Farooqui Akhlaq A. , Liss Leopold , Horrocks Lloyd A.
Published: August 2007

Two plasma membrane fractions were obtained from different regions of brains from patients with Alzheimer''s disease (AD) and normal aged individuals. One fraction was from synaptosomes (synaptosomal plasma membrane; SPM) and the other from glial cells and neuronal cell bodies (plasma membrane; PM). Among various regions analyzed, PM and SPM from the nucleus basalis of AD brains displayed 6- to 8-fold higher activities of mono- and diacylglycerol lipases than membranes from age-matched normal individuals. Membranes from the hippocampus region of AD brains also showed consistently higher activities of lipases than those from control brains. Similarly, the lysophospholipase activity in the cytosolic fraction of these regions also showed higher activity (4- to 6-fold) in AD than in corresponding fractions from normal human brains. The cause of increased activities of lipases and lysophospholipases in the nucleus basalis and hippocampus regions is not understood. However, marked elevations of acylhydrolases in the above regions may be due to overexpression, changes in levels of neuropeptides, intracellular calcium ions and/or lipid peroxides. All these are known to stimulate acylhydrolases. Autolytic changes which occur in the brain after death may markedly affect the activities of mono- and diacylglycerol lipases.
Slowly Progressive Apraxia without Dementia
Authors: Piccirilli Massimo , D'Alessandro Patrizia , Ferroni Angelo
Published: August 2007

A patient is described who showed slowly progressive apraxia not associated with other neuropsychological dysfunctions. The onset of symptoms began at age 60 years, and the duration of illness was 5 years. A further 12-month neuropsychological follow-up study failed to show any evolution of memory and other cognitive disorders. MRI revealed diffuse cortical atrophy with a very marked bilateral involvement of the parietal structures. The patient is considered as presenting slowly progressive apraxia without dementia, a syndrome that seems to be distinguishable from dementia of Alzheimer''s type.
Cerebrospinal Fluid Neuropeptide Y-Like Immunoreactive Levels in Dementia of Alzheimer Type and Dementia with Frontotemporal Degeneration of Non-Alzheimer Type
Authors: Minthon L. , Edvinsson L. , Ekman R. , Gustafson L.
Published: August 2007

Several neurochemical abnormalities are known in dementia of Alzheimer type (DAT). Little is known about the neurochemical changes in dementia with frontotemporal cortical degeneration of non-Alzheimer type (FTD), including Pick's disease. The present study evaluates the cerebrospinal fluid (CSF) levels of neuropeptide Y-like immunoreactivity (NPY-LI) correlated with duration of the disease. There was a significant difference between NPY-LI in DAT and FTD. NPY-LI is reduced in DAT but not in FTD. In FTD the CSF levels of NPY-LI tended to increase with the duration of the disease while in DAT the NPY-LI levels tended to decrease. This points towards a different involvement of NPY neurons in these two types of primary degenerative dementias.
Effects of Indeloxazine Administration on Neurotransmitters in the Cerebrospinal Fluid of Patients with Dementia of Alzheimer Type
Authors: Urakami K. , Takahashi K. , Adachi Y. , Matsushima E. , Sano K. , Saito H.
Published: August 2007

We administered indeloxazine hydrochloride to patients with dementia of Alzheimer type and evaluated clinical effects and changes in neurotransmitters in the cerebrospinal fluid (CSF). After the administration, homovanillic acid and somatostatin in the CSF did not decrease, but 5-hydroxyindoIeacetic acid, 3-methoxy-4-phenylethylenglycol, and acetylcholinesterase significantly decreased. Improvement of emotional function in Gottfries, BrÅne and Steen scale may correlate with the decrease in the CSF.
Potential Applications for Monoamine Oxidase B Inhibitors. pp 323–334
Authors: Kabins Darryl , Gershon Samuel
Published: August 2007

Monoamine oxidase inhibitors (MAOIs) are not only effective antidepressants, but also have several other applications. Yet, they are infrequently used as a result of their potential to cause toxic side effects such as tyramine-induced hypertensive crisis (cheese effect). A resurgence of interest in MAOIs followed the finding of two forms of MAO. This resulted from the development of drugs that selectively inhibit the metabolism of serotonin and norepinephrine (MAO-A) or dopamine and phenethylamine (MAO-B). MAO-B is the predominant MAO found in the human brain. Theoretically, selective MAO-B inhibition can enhance brain MAO levels while leaving intestinal MAO-A intact, thus bypassing the cheese effect, L-deprenyl is the most extensively studied MAO-B inhibitor. At low doses, it is very selective for MAO-B and is not associated with the cheese effect. At higher doses, it is virtually nonselective. L-deprenyl enhances the effect of L-dopa on Parkinson's disease and may retard its natural progression. Although studies have found L-deprenyl to be an effective antidepressant only at nonselective doses, certain subtypes of depression may respond to selective doses. Also, evidence suggests that L-deprenyl has a positive effect on the general function and cognitive abilities of Alzheimer patients. Studies to date, including those showing a significant increase in the life span of rats following L-deprenyl use have led to the speculation that L-deprenyl may not only treat or retard degenerative diseases and acute brain insults, but may prove to be the first antiaging medication. Several other potential applications of MAO-B inhibitors include panic, ADHD, sexual dysfunction, and PTSD. It remains unclear what role MAO-B inhibition plays in the various therapeutic effects of L-deprenyl. Other potential mechanisms are discussed.
Cerebrospinal Fluid Cytology in Alzheimer's Disease
Authors: Blennow Kaj , Rybo Elisabeth , Wallin Anders , Gottfries Carl-Gerhard , Svennerholm Lars
Published: August 2007

Cerebrospinal fluid (CSF) of 70 patients with Alzheimer''s disease (AD) and 36 age-matched healthy controls was examined for signs of immunological abnormality. In healthy adults, the CSF cytological picture was dominated by small lymphocytes and monocytes, together accounting for about 98% of cells. There were no changes related to sex or age in the cell composition. In the AD group, there was an increased percentage of monocytes compared with controls, but with great overlap between groups. Five AD patients displayed intrathecal synthesis of IgG, without a concomitant increase in the number of leukocytes, or a change in the cytological picture. This study shows that there is no major change in the cell-mediated immune system in AD. The discrete disturbance in the CSF cytological picture in AD may be a secondary phenomenon related to the cerebral degeneration.
Abnormal Cerebral Ventricular Change in Alzheimer's Disease Recorded with Cardiac Gated MRI: A Preliminary Report
Authors: Powell Artiss L. , Mezrich Reuben S. , Wang Jin-zhao
Published: August 2007

We compare high-resolution cardiac gated brain magnetic resonance imaging of 19 young healthy subjects with a small group of demented subjects - mainly probable senile dementia of the Alzheimer type (SDAT) - with varying degrees of ventricular enlargement. Computer-measured ventricular volume demonstrated cyclic ventricular size variations in all subjects. During cardiac systole, the lateral ventricles vary in size, an average of 10% in the young cohort (0.109 ± 0.061); the lateral ventricles enlarge, often after an initial decrease in size. A later volume expansion may occur, but the amount varies between subjects. One healthy 60-year-old subject, whose ventricles were slightly larger than those of the younger individuals, and all of the demented subjects, had less enlargement when compared to the average young subject. Two demented subjects with ventriculomegaly had small fluctuations: one had only 6.9% variation, the other subject with larger ventricles had no enlargement. One individual with SDAT had more than a 24% volume change while another subject''s increase was delayed. Our results suggest a complex interplay between blood flow, brain compliance and CSF outflow resistance. This small study further suggests that the choroid plexus plays an important role in systole-related lateral ventricular changes, that changes in choroid plexus function may occur in hydrocephalus and that CSF dynamics may be impaired in SDAT disease.
Relationship between Hypertension and Early Indicators of Cognitive Decline
Authors: Fioravanti Mario , Agazzani Daniela , D'Ilario Daniele , Di Veroli Claudio , Turchetti Gian Franco
Published: August 2007

In patients with cerebrovascular disease the identification of risk factors might be hypothesized as being associated with the beginning of the process leading, in some of cases, to dementia. The studies described in this paper were designed to verify this hypothesis. The first study showed that specific signs of memory and attention impairment can be identified when hypertensives are compared to normal subjects of the same age. The second study demonstrated that these cognitive deficits are not evenly distributed among hypertensives (about one half of the patients do not show signs of these deficits) and that when signs are present they are independent of interference from emotional problems.
Inoculation Study of Alzheimer Buffy Coat into Hamster Brain
Authors: Takeda Masatoshi , Nishimura Tsuyoshi , Tada Kunitoshi , Kudo Takashi , Tanimukai Satoshi
Published: August 2007

Buffy coats from 4 members of a family with Alzheimer''s disease and 2 genetically unrelated healthy subjects were inoculated into the hamster brain. Eighteen months after the inoculation, the brains were studied by immunostaining with antibodies against neurofilaments, tau, ubiquitin, and paired-helical filaments (PHF) as well as by electron microscopy. Vacuolar or spongioform degeneration was minimum. Intense positive staining by antibodies against neurofilament 200K protein was demonstrated in neuronal perikarya of the lower brain stem nucleus in the hamster inoculated with the buffy coats from the 2 patients with Alzheimer''s disease and 2 children of the patient, which was not observed in the hamster brain inoculated with the buffy coat from the control subjects. Electron microscopy revealed intracytoplasmic accumulation of 10-nm neurofilament-like fibers. The accumulated neurofilaments were positively stained by antitau and antiubiquitin, but not by anti-PHF. The neurons containing massive intracytoplasmic neurofilament accumulation resembled ballooned neurons in some degenerative diseases including Alzheimer''s disease. The results indicate that the buffy coat obtained from the patients and members of a family with Alzheimer''s disease contains a factor which produces intracytoplasmic accumulation of neurofilament-like fibers in neurons of the lower brain stem nuclei.
Preservation of Somatostatin Receptors Coupled to the Inhibition of Adenylate Cyclase in the Cortex and Hippocampus in Senile Dementia of the Alzheimer Type
Authors: Slama A. , Heidet V. , Cervera P. , Hirsch E. , Javoy-Agid F. , Epelbaum J.
Published: August 2007

The distribution and the density of 125I-Tyr0-DTrp8-somatostatin (125I-SRIF) binding sites were compared by quantitative radioautography in the hippocampi and entorhinal cortices from normal humans and patients with senile dementia of the Alzheimer type (SDAT). In SDAT, entorhinal cortex concentrations of choline acetyl transferase and SRIF were significantly decreased as compared to controls. The neuroanatomical distribution of I25I-SRIF binding sites was similar in control and SDAT hippocampus and entorhinal cortex, being high in molecular layers of the dentate gyrus and stratum oriens of the CA1 and deeper cortical layers (V-VI), intermediate in superficial (II—III) cortical layers and low in subiculum, hilus of the dentate gyrus and cortical layer I and IV. Competition curves with SMS 201995 to displace 125I-SRIF binding allowed to differentiate between high (SS-A)-and low (SS-B)-affinity somatostatin binding sites. In control brains, SS A (Kd A = 0.06 ± 0.02 nM) represented 23–33% of the binding while SS B (KdB = 23.5 ± 2.8 nM) accounted for 67–77% of total specific binding, depending on the regions. In dentate gyrus and CA1, the proportion of SS-A was significantly reduced in SDAT as compared to controls. The reduction did not reach significance in the entorhinal cortex, and inhibition of adenylate cyclase activity by SRIF was equivalent in SDAT and controls. It is concluded from these data that the number of SS-A decreases in SDAT hippocampus but that SS-B and negative coupling to adenylate cyclase are preserved.
Galanin Tuberomammillary Neurons in the Hypothalamus in Normal Patients and in Senile Dementia of the Alzheimer Type
Authors: Chan-Palay V. , Jentsch B.
Published: August 2007

The galanin immunoreactive neurons of the tuberomammillary nuclei of the hypothalamus in the human brain were studied in controls and in patients with senile dementia of the Alzheimer type. Galanin neurons are found in compact groups and loosely distributed in distinct locations throughout this nucleus. The nuclear topography is described by the reconstruction of serial sections and displayed in computer generated displays in the third dimension. There are cellular changes and cell loss in the galanin neurons in Alzheimer''s disease, however these changes are not consistent and individual variation is high. The most consistent changes are found in cell loss with increasing age.
Altered EEG Dynamical Responsivity Associated with Normal Aging and Probable Alzheimer's Disease
Authors: Pritchard Walter S. , Duke Dennis W. , Coburn Kerry L.
Published: August 2007

The Takens-Ellner method was employed to estimate the dimensional complexity of topographic EEG data (resting, eyes-closed and eyes-open) in 3 subject groups: normal young, normal elderly, and elderly probable Alzheimer''s (PA) patients. Similar overall dimensional complexity levels as well as similar patterns of variation across the scalp were found in all 3 groups. In the normal young group, eyes-open dimensional complexity was markedly higher than eyes-closed dimensional complexity. A similar but somewhat weaker pattern was seen in the normal elderly group. In the PA patients, eyes-open dimensional complexity did not differ from eyes-closed dimensional complexity. It is concluded that Alzheimer''s disease may be associated with a loss of dynamical brain responsivity to the environment rather than a global loss of dimension.
Dementia: Nosology and Brain-Behavior Relationships
Authors: Chatterjee Anjan , Mack James , Whitehouse Peter J.
Published: August 2007

This paper is an analysis of some conceptual difficulties involved in diagnosing dementia with particular reference to the question of the existence of dementia subtypes. Investigators have attempted to elucidate clinico-pathologic correlations underlying dementia by introducing the categories of cortical and subcortical dementias. Before the results of neuropathology and neuropsychologic data can be interpreted, however, one must consider the definitional nature of dementia itself. It may be an oversimplification to assign all dementias to one or the other of these superordinate categories. A closer look at the nosology of dementia reveals the inherent ambiguity of definitions used. As a consequence of this ambiguity, qualitatively different disorders have been compared as if they were quantitatively different. A framework for rational comparisons is provided by which dementing syndromes may be used to further our understanding of brain-behavior relationships.
Neurofibrillary Pathology in Subacute Sclerosing Panencephalitis
Authors: Wisniewski Henryk M. , Dymecki Jerzy , Wegiel Jerzy , Kulczycki Jerzy , Schmidt-Sidor Bogna , Grundke-Iqbal Inge , Strojny Pawel
Published: August 2007

Neurofibrillary changes are characteristic of the brains of individuals with Alzheimer''s disease (AD) and of those with Down syndrome. Neurofibrillary tangles (NFT) are also seen in small numbers in the brains of normal old people. They also occur in subacute sclerosing panencephalitis (SSPE), a fatal inflammatory disease induced by measles virus. The aim of this study of 44 autopsy cases of SSPE was to estimate the frequency of NFT in this subpopulation, their topography and distribution, as well as the stage of NFT maturation. Nine specimens from the cortex, hippocampus, mesencephalon, and pons of 38 brains and 6 specimens from the cortex of six other brains were used. We used silver impregnation (Bodian-PAS and Bielschowsky techniques), thioflavine S, and immunoreactivity with monoclonal antibodies (mAbs) to tau-1, paired helical filaments (PHF)/ubiquitin 3–39, GFAP, and beta-amyloid protein 4G8. NFT were found in 8 cases (18.2%). Their number was extremely variable individually. In 5 cases, morphometric studies were performed. The average number of pretangle- and NFT -positive neurons in the brain structures examined ranged from 1.1/mm2 in the case with the shortest duration of disease (27 months) to 43.8/mm2 in the case with the longest duration (14 years). In spite of the young age (9–31 years) of the patients with SSPE, the number of NFT in some cases was comparable to the number observed in AD. In 5 cases, NFT were present in the hippocampus as well as in the entorhinal, temporal, and insular cortices. In 6 cases, the frontal, and in 4 cases, the parietal and occipital cortices were involved. About 25% (SE= 4.42) of the abnormal neurons in the cortex constituted pretangle neurons with granular, argentophilic material that is tau-1 positive, but PHF/ubiquitin 3–39 negative. Another 27.4% were early tangles (stage 1) (SE = 0.82). Mature tangles (stage 2) were more numerous and constituted 47.55% (SE = 3.93) of all tangles. Ghost tangles (stage 3) were not found.
Detection of Visual Memory and Learning Deficits in Alzheimer's Disease Using the Cambridge Neuropsychological Test Automated Battery
Authors: Sahgal Arjun , Sahakian Barbara J. , Robbins Trevor W. , Wray Catherine J. , Lloyd Stephen , Cook Julia H. , McKeith Ian G. , Disley Jennifer C.A. , Eagger Sarah , Boddington Stephen , Edwardson James A.
Published: August 2007

Alzheimer''s disease (AD) is characterized by marked cognitive and especially mnemonic decline. Microcomputer controlled tests offer a powerful method for assessing these impairments, since precise control over stimulus presentation and responding can be achieved. The recently described CANTAB© (Cambridge Neuropsychological Test Automated Battery) procedure includes a number of visual tasks which can help to pinpoint these deficiencies with accuracy. Using some of the tests available, we describe impairments in nonverbal visual recognition, memory and learning seen in AD.
GH Response to GH-Releasing Factor in Dementia and Its Relation with TSH Response to TSH-Releasing Factor
Authors: Gómez Sáez J.M. , Aguilar Barberá M.
Published: August 2007

We have studied the GH response to GH-releasing factor (GRF) and the TSH response to TSH-releasing factor (TRH) in two groups of patients with dementia. A group of 28 patients with Alzheimer''s disease (AD) and another group of 28 patients with dementia of vascular origin (VD). The GH response to GRF exhibited no difference between AD and VD patients (12.2 ± 2.05 vs. 9.96 ± 1.44 µg/ml) and there was no correlation between the response of GH to GRF and sex, stage of the disease and cerebral atrophy. The numbers of cases with exaggerated, normal or without response were similar in AD and VD patients. The TSH response to TRH exhibited no difference between AD and VD patients (9.18 ± 0.9 vs. 10.35 ± 1.2 mU/ml). There was no correlation between TSH response to TRH and sex, stage of the disease, cerebral atrophy and response of GH to GRF. The number of cases with exaggerated, normal or without response were similar in AD and VD patients. It would appear that the response of GH to GRF is not useful as a diagnostic aid in AD patients, because the response is similar in VD patients.
Tetrahydroaminoacridine in Alzheimer's Disease: A Review of Its Safety and Its Effectivness
Authors: Chatellier Gilles , Lacomblez Lucette , Derouesne Christian
Published: August 2007

Tetrahydroaminoacridine (THA) is a potent centrally acting anticholinesterase which has been used by anesthesiologists since the 1940s. The report by Summers et al. of encouraging results with this compound in Alzheimer''s disease was greeted with enthusiasm by both the general public and the media. Since this first publication, two relatively large clinical trials and many small-sized trials evaluating THA in Alzheimer''s disease have been published. The two larger trials had sufficient power to detect effects of the magnitude reported in the original study by Summers et al. Two conclusions can be drawn from these trials. First, THA causes substantial elevations of liver enzymes in a sizable fraction of patients. Second, the cognitive effect of THA is probably small. We conclude that, until the American multiclinical trial is completed, THA must remain a research drug used in therapeutic trials.
Parallel Group Analysis of the Effects of Tacrine versus Placebo in Alzheimer's Disease
Authors: Eagger Sarah A. , Morant Nicola J. , Levy Raymond
Published: August 2007

In the light of prevailing views about the difficulty of analysing data from cross-over trials in Alzheimer''s disease and the increasing emphasis being placed on the possible clinical relevance of statistically significant changes in test scores we have examined the results of a recently reported clinical trial of tacrine. For this purpose we have analysed the first half of our cross-over trial as a parallel group study involving 73 patients. The previously reported significant changes in MMSE in drug versus placebo groups was held up in this analysis (p < 0.001). We have also extracted clinician and carers'' comments from the case notes. These comments were rated blindly by two independent psychologists on a 5-point scale. These retrospective ratings clearly favoured the tacrine group (p = 0.0004) although they have to be viewed critically in view of the post-hoc nature of the procedure. It is concluded that tacrine did indeed appear to produce clinically relevant improvements when compared to placebo and that these were evident in parallel groups as well as in our previous cross-over trial. They could not be attributed to changes in mood.
βA4 Amyloid Protein Deposition in the Cerebellum in Alzheimer's Disease and Down's Syndrome
Authors: Mackenzie I.R.A. , McKelvie P.A. , Beyreuther K. , Masters C.L.
Published: August 2007

The cerebellum shows pathological changes in most cases of Alzheimer''s disease (AD). Previous reports have stressed the presence of elongated, diffuse deposits of βA4 protein in the molecular layer as the major lesion. We have examined cerebellar tissue from 20 cases of sporadic AD, 8 cases of familial AD and 2 adult Down''s syndrome (DS) patients using βA4 immunohistochemistry. As well as the molecular layer lesions, we found diffuse deposits of βA4 protein around Purkinje cells to be a common lesion and in one DS case, the only significant pathologic change. These deposits were often contiguous with the elongated deposits in the molecular layer. We propose that βA4 protein may be initially deposited in the extracellular space around Purkinje cells and then migrates by bulk flow through the molecular layer towards the pial surface.
Cerebral Amyloid Angiopathy in Alzheimer's Disease: Clinicopathological Correlations
Authors: Lopez Oscar L. , Claassen Diana
Published: August 2007

The presence of cerebral amyloid angiopathy (CAA) in capillaries and arterioles of the cerebral and cerebellar cortex of Alzheimer's disease (AD) patients may provide an opportunity to study the clinical significance of these vascular changes in AD. We reviewed the clinical and pathological features of 40 patients with AD without other CNS disease. The sections were examined by the red Congo method under a polarized light for the presence of CAA. Twenty-two (55%) had AD + CAA. CAA was seen most frequently and was of greater severity in occipital and frontal gray matter. We concluded that it is not possible to differentiate between AD patients with CAA and those without CAA in terms of demographic characteristics and neurological and psychiatric symptomatology.
Angiotensin II Immunoreactivity in the Human Striatum and Hippocampus of Elderly Controls and Patients with Senile Dementia of the Alzheimer Type and Multi-Infarct Dementia
Authors: Savaskan Egemen , Höchli Mathias , Ganten Detlev , Chan-Palay Victoria
Published: August 2007

The distribution of angiotensin II (A II) immunoreactivity in the postmortem human corpus striatum was studied in control cases and in patients with senile dementia of the Alzheimer type (SDAT) and multi-infarct dementia (MID). Additionally A II immunoreactivity was examined in the hippocampus of control and SDAT patients. A II-immunopositive cellular structures found in the striatum were the large neurons and vesiculated fibers in the globus pallidus (GP), especially in the dorsal parts, and some aspiny neurons in the putamen. Changes in the cell morphology marked the neurons in the GP of SDAT patients. In the MID cases only a few A II-immunopositive fibers and no cell somata were present in the GP. An extracellular, perivascular A II-staining pattern, which was found only in 1 control case, was common to all SDAT and MID patients. A II-immunopositive cellular structures found in the hippocampus included distorted neuronal processes and vesiculated fibers, which were partly coexisting with neuritic plaques as shown by the double labeling with thioflavin. The perivascular A II staining was also observed in the hippocampus, which was more predominant in SDAT cases. The definition of these two A II-immunopositive cell types in human corpus striatum suggests that A II may be involved in local neuronal or projection pathways. Possibly A II participates in the development of cerebrovascular pathologies in elderly control and demented brains.
Brain Damage Caused by Ischemia: Pathophysiological and Pharmacological Aspects
Authors: Rami Abdelhaq , Krieglstein Josef
Published: August 2007

The distribution of brain cell injury after ischemic challenge is remarkable because only discrete brain areas are damaged, whereas other structures exhibit a very high resistance (selective neuronal death). The calcium hypothesis, one of the hypotheses that has been formulated to explain this selective vulnerability, postulates that an increase in excitatory amino acid release and the large calcium influx during ischemia leads to insufficient energy production and to stimulation of lipases, proteases, and endonucleases. This paper reviews the experimental data concerning the relationship between cerebral blood flow, glucose consumption and hippocampal morphological damage. The neuroprotective effects of some drugs against ischemic damage have also been discussed.