Evaluation of CSF-Chlamydia pneumoniae,CSF-tau,and CSF-Abeta42 in Alzheimer’s disease and vascular dementia

The potential role of microbiological factors such as Chlamydia pneumoniae (ChP) in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease (AD) and vascular dementia (VD), has been suggested, but the correctness of this hypothesis still needs to be tested. In this study the appearance of ChP in the cerebrospinal fluid (CSF) of 57 AD and 21 VD patients and in 47 controls (CG) as well as the influence of ChP on the levels of tau protein and Abeta42 were investigated. The frequency of ChP occurrence in the AD patient group (43.9%) was significantly higher (p < 0.001) than in the control group (10.6%). In the case of VD patients, 9.5% of this group was positive for ChP. The presence of ChP DNA in the CSF of patients with AD significantly increases the occurrence of this disease (odds ratio = 7.21). Cerebrospinal fluid Abeta42 levels were significantly lower in patients with AD than in the CG (p < 0.001). Cerebrospinal tau protein was significantly higher in AD vs. CG (p = 0.007). However, no relationships between the presence of the bacterium in CSF and the level of either tau or Abeta42 protein were observed. In conclusion, we may suspect that testing for the presence of ChP in CSF, along with the tau and Abeta42 markers, may be used in the clinic diagnosis of AD.     

Temporally graded activation of neocortical regions in response to memories of different ages

The temporally graded memory impairment seen in many neurobehavioral disorders implies different neuroanatomical pathways and/or cognitive mechanisms involved in storage and retrieval of memories of different ages. A dynamic interaction between medial-temporal and neocortical brain regions has been proposed to account for memory's greater permanence with time. Despite considerable debate concerning its time-dependent role in memory retrieval, medial-temporal lobe activity has been well studied. However, the relative participation of neocortical regions in recent and remote memory retrieval has received much less attention. Using functional magnetic resonance imaging, we demonstrate robust, temporally graded signal differences in posterior cingulate, right middle frontal, right fusiform, and left middle temporal regions in healthy older adults during famous name identification from two disparate time epochs. Importantly, no neocortical regions demonstrated greater response to older than to recent stimuli. Our results suggest a possible role of these neocortical regions in temporally dating items in memory and in establishing and maintaining memory traces throughout the lifespan. Theoretical implications of these findings for the two dominant models of remote memory functioning (Consolidation Theory and Multiple Trace Theory) are discussed.     

Sensory learning-induced enhancement of inhibitory synaptic transmission in the barrel cortex of the mouse

In adult mice, repetitive pairing of stimulation of mystacial vibrissae with an electrical shock to the tail induces expansion of the cortical representation of stimulated vibrissae accompanied by elevation of the GABAergic markers. Here, we show that this associative learning paradigm results in a selective increase in the frequency of spontaneous inhibitory postsynaptic currents in layer IV excitatory neurons located within the barrel representing stimulated vibrissae, evident 24 h after the end of training. The mean amplitude of spontaneous inhibitory postsynaptic potentials recorded from excitatory neurons was unchanged. Recordings from layer IV excitatory and fast spiking neurons showed that the training induced changes neither in the mean frequency nor it the mean amplitude of spontaneous excitatory postsynaptic currents. On the other hand, the mean amplitude of field potentials evoked by the stimulation of layer VI and recorded in layer IV was significantly reduced. These data indicate that aversive training results in a selective and long-lasting enhancement of GABAergic transmission within the cortical representation of stimulated vibrissae, which may result in a decrease in layer VI-evoked field responses.     

Giant cell ependymoma: a case report

Ependymomas account for 3-9% of all neuroepithelial tumors. A peculiar variant of ependymoma known as "giant cell ependymoma" ("GCE") is especially rarely reported, it may pose some difficulties for the diagnosing neuropathologist. Here we present a case of a giant cell ependymoma occuring in a 17-year-old patient with the history of 2-year recurrent headaches and a 1-month history of vision impairment. CT scanning demonstrated a mass in the left occipital lobe, arising from the occipital horn of the lateral ventricle. Histological, immunohistochemical and electron microscopic findings were consistent with high-grade ependymoma. Especially striking was the presence of bizzare pleomorphic giant cells which predominated in the tumor tissue. As a result the diagnosis of GCE was established. This type of neoplasm necessitates, at least in theory, differentiation with anaplastic oligodendroglioma, clear cell ependymoma, pleomorphic xanthoastrocytoma, giant cell glioblastoma, and subependymal giant cell astrocytoma. To date giant cell ependymomas (GCEs) were reported in seven cases in the literature. To the best of our knowledge this is the 8th case in the literature. In spite of apparently "worrisome" histology GCE seems to be a neoplasm with a relatively good prognosis.     

Sensorimotor tongue representation in individuals with unilateral upper limb amelia

The purpose of the present study was to examine the impact of the congenital absence of one hand on cortical organization of the sensorimotor cortex (S1/M1). We investigated the tongue representation in S1/M1 in nine participants with normally developed limbs, comprising the control group, and in eight persons with a congenitally completely missing hand (i.e. unilateral hand amelia). All participants were examined by fMRI while performing horizontal tongue movements. The significantly activated clusters covering S1/M1 in both hemispheres were analyzed with respect to the number and intensity of activated voxels, as well as the location of the activation. In the right-handed control group, the number of activated voxels was significantly higher in the left as compared to the right hemisphere demonstrating a clear left hemispheric motor dominance for horizontal tongue movements. In the amelic individuals, no such hemispheric lateralization effect was observed. The neural activation pattern underlying tongue movement, however, was enlarged and displaced in the hemisphere contralateral to the missing limb when compared to the respective motor non-dominant, right hemisphere of the control group participants. The present findings suggest that congenital absence of one hand leads to an appreciably altered topological organization of S1/M1 consisting of an enlargement of the tongue representation and a shift towards the "hand" area which, however, had never received any input from a hand.     

Diagnostic potential of oxidative stress markers in children and adolescents with type 1 diabetes

OBJECTIVES: To validate the diagnostic utility of oxidative stress markers in the evaluation of young type 1 diabetics, as suggested elsewhere. DESIGN: Advanced oxidation protein products (AOPP), thiobarbituric acid-reactive substances (TBARS) and total antioxidant status (TAS) were measured in sera from diabetics, their siblings and controls, with diagnostic potential evaluated by ROC analysis, and related to diabetes clinical parameters. RESULTS: In diabetics AOPP and TBARS were elevated, TAS decreased. Similar alterations were observed for AOPP and TAS in their siblings. AOPP and TAS were good indicators of diabetes. AOPP and TBARS correlated with HbA1C (independent predictor), but were poor markers of non-adequate glycemic control. The cardiovascular disease risk factors were independent predictors of TBARS concentrations. CONCLUSIONS: AOPP accumulation and TAS reduction seem to precede diabetes and might be considered as susceptibility indicators in relatives, but not as diabetes markers in general population (no diabetes specificity has been shown). Application in monitoring of metabolic control is not validated.     

Evaluation of 8-hydroxydeoxyguanosine, thiobarbituric acid-reactive substances and total antioxidant status as possible disease markers in oesophageal malignancies

ObjectivesEvaluation of oxidative stress and diagnostic utility of its markers in oesophageal squamous cell carcinoma (OSCC).DesignSerum 8-hydroxydeoxyguanosine, thiobarbituric acid-reactive substances (TBARS) and total antioxidant status (TAS) were measured in OSCC (n = 75), non-malignant oesophageal diseases (n = 30), and healthy subjects (n = 79). Three months following oesophagectomy the measurements were repeated.ResultsExclusively in OSCC, 8-hydroxydeoxyguanosine and TBARS were elevated. TAS was reduced in non-malignancies compared to controls, and in OSCC compared to non-malignancies and controls. Only 8-hydroxydeoxyguanosine was associated with disease progression, lymph node involvement in particular. All indices were good indicators of cancer presence (ROC analysis) and normalized following oesophagectomy. A positive linear relationship between 8-hydroxydeoxyguanosine and TBARS, and negative non-linear between TAS and both 8-hydroxydeoxyguanosine and TBARS was demonstrated.ConclusionOSCC is associated with oxidative stress, attenuated following oesophagectomy. Consumption of serum antioxidants prevents accumulation of oxidatively modified molecules in non-malignancies. High accuracy of oxidative stress markers in indicating cancer presence warrants further investigation on their possible application as discriminatory markers and in monitoring treatment efficacy.     

Initial evaluation of new 99mTc(CO)3 renal imaging agents having carboxyl-rich thioether ligands and chemical characterization of ReCO3 analogues

INTRODUCTION: The first human studies of a characterized radiopharmaceutical containing a {(99m)Tc(CO)(3)}(+) core, Na[(99m)Tc(CO)(3)(LAN)], demonstrated that Na[(99m)Tc(CO)(3)(LAN)] was an excellent renal imaging agent; however, its clearance was less than that of (131)I-orthoiodohippurate ((131)I-OIH), and it did not provide a direct measure of effective renal plasma flow. In order to develop a (99m)Tc renal agent with pharmacokinetic properties equivalent to those of (131)I-OIH, we investigated the (99m)Tc(CO)(3)/Re(CO)(3) complexes formed from carboxymethylmercaptosuccinic acid (CMSAH(3)) and thiodisuccinic acid (TDSAH(4)). Once the ligand is bound to (99m)Tc(CO)(3) through a thioether and two carboxyl groups, the complexes have at least one unbound carboxyl group, essential for the interaction with the renal tubular transporter. METHODS: X-ray crystal structural analysis of [NMe(4)][Re(CO)(3)(CMSAH)] was performed to interpret the nature of (99m)Tc tracers. CMSAH(3) and TDSAH(4) were radiolabeled by incubating each ligand and the precursor [(99m)Tc(CO)(3)(H(2)O)(3)](+) at 70 degrees C (pH 7) for 30 min. The products were purified by reversed-phase high-performance liquid chromatography, and biodistribution studies were performed in Sprague-Dawley rats, with (131)I-OIH as an internal control at 10 and 60 min. RESULTS: Radiolabeling CMSAH(3) and TDSAH(4) with the [(99m)Tc(CO)(3)(H(2)O)(3)](+) precursor gave products quantitatively. Analysis of the Re(CO)(3) complexes with the CMSAH(3) and TDSAH(4) ligands demonstrates that ligands are bound in (99m)Tc/Re(CO)(3) complexes through a thioether and two deprotonated carboxyl groups (forming tridentate dianionic moieties, generally with two 5-membered chelate rings). Renal excretion at 60 min (activity in the urine as a percentage of (131)I-OIH) was 68+/-1% for Na(3)[(99m)Tc(CO)(3)(TDSA)] but was 98+/-1% for Na(2)[(99m)Tc(CO)(3)(CMSA)]. CONCLUSION: In rats, Na(2)[(99m)Tc(CO)(3)(CMSA)] is extracted by the kidneys and eliminated in the urine almost as rapidly as (131)I-OIH; consequently, Na(2)[(99m)Tc(CO)(3)(CMSA)] may provide a direct measure of effective renal plasma flow, and further evaluation in humans is warranted.