Lateral ventricle differences between first-episode schizophrenia and first-episode psychotic bipolar disorder: A population-based morphometric MRI study

Objectives. The extent to which psychotic disorders fall into distinct diagnostic categories or can be regarded as lying on a single continuum is controversial. We compared lateral ventricle volumes between a large sample of patients with first-episode schizophrenia or bipolar disorder and a healthy control group from the same neighbourhood. Methods. Population-based MRI study with 88 first-episode psychosis (FEP) patients, grouped into those with schizophrenia/schizophreniform disorder (N = 62), bipolar disorder (N = 26) and 94 controls. Results. Right and left lateral ventricular and right temporal horn volumes were larger in FEP subjects than controls. Within the FEP sample, post-hoc tests revealed larger left lateral ventricles and larger right and left temporal horns in schizophrenia subjects relative to controls, while there was no difference between patients with bipolar disorder and controls. None of the findings was attributable to effects of antipsychotics. Conclusions. This large-sample population-based MRI study showed that neuroanatomical abnormalities in subjects with schizophrenia relative to controls from the same neighbourhood are evident at the first episode of illness, but are not detectable in bipolar disorder patients. These data are consistent with a model of psychosis in which early brain insults of neurodevelopmental origin are more relevant to schizophrenia than to bipolar disorder.

Profiles of functional deficits in mild cognitive impairment and dementia: benefits from objective measurement

The magnitude Of functional impairment that may indicate the threshold between MCI and incipient Alzheimer`s disease (AD) has not been clearly defined. The objective was to examine the pattern of functional impairment in the continuum MCI-AD. Eighty-nine older adults (32 cognitively unimpaired, 31 MCI, and 26 AD patients) were examined with the Brazilian version of the Direct Assessment of Functional Status (DAFS-BR) at a University-based memory clinic. MCI patients were sub-divided according to the progression to AD upon follow-up, and had baseline cognitive, functional and biological variables analyzed. MCI patients displayed mild deficits in functional abilities, with intermediate scores as compared to controls and AD. The DAFS-BR items that differentiated MCI from controls involved the ability to deal with finances and shopping skills. At baseline, scores obtained by MCI patients who converted to AD were not significantly different from scores of nonconverters. The magnitude of functional deficits was associated with AD-like pathological findings in the CSF. In conclusion, MCI patients present with early functional changes in complex, instrumental abilities that require the integrity of memory and executive functions. The objective measurement of the functional state may help identify older adults with increased risk of developing dementia in the MCI-AD continuum. (JINS, 2010, 16, 297-305.)

Post-transplant recurrent hepatitis C: immunohistochemical detection of hepatitis C virus core antigen and possible pathogenic implications

Introduction: The mechanisms by which severe cholestatic hepatitis develops after liver transplantation are not fully understood. Reports on immunohistochemical distribution of hepatitis C virus (HCV) antigens are still scarce, but recently, HCV immunostaining was suggested for early diagnosis of cholestatic forms of recurrent hepatitis C in liver grafts. After purification, Rb246 pab anticore (aa1-68) yielded specific, granular cytoplasmic staining in hepatocytes. Signal amplification through the Envision-Alkaline Phosphatase System avoided endogenous biotin and peroxidase. Aims/Methods: Rb246 was applied to liver samples of explants of 12 transplant recipients, six with the most severe form of post-transplantation recurrence, severe cholestatic hepatitis (group 1) and six with mild recurrence (group 2). We also assessed immuno-reactivity at two time-points post-transplantation (median 4 and 22 months) in both groups. HCV-core Ag was semiquantified from 0 to 3+ in each time point. Serum HCV-RNA was also measured on the different time points by branched DNA. Results: In the early post-transplant time point, one patient had a mild staining (1+), two patients had a moderate staining (2+) and the other three had no staining in group 1, compared with five patients with no staining (0) and one patient with mild staining (1+) in group 2. Late post-transplant liver samples were available in nine patients, and two out of four samples in group 1 showed a mild staining, compared with no staining patients in five patients in group 2. Strikingly, on the explant samples, HCV immunostaining was strongly positive in group 1, and mildly positive in group 2. Two out of five samples showed 3+ staining, and three samples showed 2+ staining in group 1; two out of five samples showed no staining, two samples showed 1+ staining and one sample showed 2+ staining in group 2. Serum HCV-RNA was significantly higher in group 1, on both time-points post-transplantation. HCV-core Ag was not directly associated with serum HCV-RNA on the different time points. Conclusion: These preliminary results suggest that strong HCV immunostaining in the explant is predictive of more severe disease recurrence.

Acromegaly: correlation between expression of somatostatin receptor subtypes and response to octreotide-lar treatment

About one-third of acromegalics are resistant to the clinically available somatostatin analogs (SA). The resistance is related to density reduction or different expression of somatostatin receptor subtypes (SSTR). This study analyzes SSTR`s expression in somatotrophinomas, comparing to SA response, hormonal levels, and tumor volume. We analyzed 39 somatotrophinomas; 49% were treated with SA. The most expressed SSTR was SSTR5, SSTR3, SSTR2, SSTR1, and SSTR4, respectively. SSTR1 and SSTR2 had higher expression in patients that had normalized GH and IGF-I. SSTR3 was more expressed in patients with tumor reduction. There was a positive correlation between the percentage of tumor reduction and SSTR1, SSTR2 and SSTR3 expression. Also, a positive correlation between SSTR2 mRNA expression and the immunohistochemical reactivity of SSTR2 was found. Our study confirmed the association between the SA response to GH and IGF-I and the SSTR2. Additionally, this finding was also demonstrated in relation to SSTR1.

Inhibition of phospholipase A(2) in rat brain decreases the levels of total Tau protein

The microtubule-associated protein Tau promotes the assembly and stability of microtubules in neuronal cells. Six Tau isoforms are expressed in adult human brain. All six isoforms become abnormally hyperphosphorylated and form neurofibrillary tangles in Alzheimer disease (AD) brains. In AD, reduced activity of phospholipase A(2) (PLA(2)), specifically of calcium-dependent cytosolic PLA(2) (cPLA(2)) and calcium-independent intracellular PLA(2) (iPLA(2)), was reported in the cerebral cortex and hippocampus, which positively correlated with the density of neurofibrillary tangles. We previously demonstrated that treatment of cultured neurons with a dual cPLA(2) and iPLA(2) inhibitor, methyl arachidonyl fluorophosphonate (MAFP), decreased total Tau levels and increased Tau phosphorylation at Ser(214) site. The aim of this study was to conduct a preliminary investigation into the effects of in vivo infusion of MAFP into rat brain on PLA(2) activity and total Tau levels in the postmortem frontal cortex and dorsal hippocampus. PLA(2) activity was measured by radioenzymatic assay and Tau levels were determined by Western blotting using the anti-Tau 6 isoforms antibody. MAFP significantly inhibited PLA(2) activity in the frontal cortex and hippocampus. The reactivity to the antibody revealed three Tau protein bands with apparent molecular weight of close to 40, 43 and 46 kDa in both brain areas. MAFP decreased the 46 kDa band intensity in the frontal cortex, and the 43 and 46 kDa band intensities in the hippocampus. The results indicate that in vivo PLA(2) inhibition in rat brain decreases the levels of total (nonphosphorylated plus phosphorylated) Tau protein and corroborate our previous in vitro findings.

Effect of brain-derived neurotrophic factor Val66Met polymorphism and serum levels on the progression of mild cognitive impairment

Objectives. Abnormalities in neurotrophic systems have been reported in Alzheimer`s disease (AD), as shown by decreased serum brain-derived neurotrophic factor (BDNF) levels and association with BDNF genetic polymorphisms. In this study, we investigate whether these findings can be detected in patients with mild cognitive impairment (MCI), which is recognized as a high risk condition for AD. We also address the impact of these variables on the progression of cognitive deficits within the MCI-AD continuum. Methods. One hundred and sixty older adults with varying degrees of cognitive impairment (30 patients with AD, 71 with MCI, and 59 healthy controls) were longitudinally assessed for up to 60 months. Baseline serum BDNF levels were determined by sandwich ELISA, and the presence of polymorphisms of BDNF and apolipoprotein E (Val66Met and APOE*E4, respectively) was determined by allelic discrimination analysis on real time PCR. Modifications of cognitive state were ascertained for non-demented subjects. Results. Mean serum BDNF levels were reduced in patients with MCI and AD, as compared to controls (509.2 +/- 210.5; 581.9 +/- 379.4; and 777.5 +/- 467.8 pg/l respectively; P < 0.001). Baseline serum BDNF levels were not associated with the progression of cognitive impairment upon follow-up in patients with MCI (progressive MCI, 750.8 +/- 463.0; stable MCI, 724.0 +/- 343.4; P = 0.8), nor with the conversion to AD. Although Val66Met polymorphisms were not associated with the cross-sectional diagnoses of MCI or AD, the presence of Met-BDNF allele was associated with a higher risk of disease-progression in patients with MCI (OR = 3.0 CI(95%) [1.2-7.8], P = 0.02). We also found a significant interaction between the APOE*E4 and Met-BDNF allele increasing the risk of progression of cognitive impairment in MCI patients (OR = 4.4 CI(95%) [1.6-12.1], P = 0.004). Conclusion. Decreased neurotrophic support, as indicated by a reduced systemic availability of BDNF, may play role in the neurodegenerative processes that underlie the continuum from MCI to AD. The presence of Met-BDNF allele, particularly in association with APOE*E4, may predict a worse cognitive outcome in patients with MCI.

Increased Serum IL-1 beta Level in Alzheimer`s Disease and Mild Cognitive Impairment

Background/Aims: Abnormal inflammatory response has been associated to the pathogenesis of Alzheimer`s disease (AD) and may be a marker of an ongoing neurodegenerative process. The aim of this study was to evaluate the serum levels of interleukin-1 beta (IL-1 beta) in patients with mild cognitive impairment (MCI) and AD. Methods: One hundred and sixty-three older adults ( 58 with mild to moderate AD, 74 with MCI and 31 healthy controls) were recruited for this study. Serum IL-1 beta levels were measured by ELISA. Patients with MCI were subcategorized in single-domain amnestic (aMCI), nonamnestic (naMCI), and multiple-domain (mdMCI) subtypes. Results: Patients with AD and MCI ( all subtypes) had a significant increase in serum IL-1 beta levels as compared to controls (p = 0.03). Patients with mdMCI had serum IL-1 beta levels comparable to those with AD, and significantly higher than those observed in aMCI and naMCI ( p = 0.02). Discussion: The present study provides evidence that inflammatory mechanisms, represented by elevated IL-1 beta, are observed in patients with MCI, specifically in those with impairment in multiple cognitive domains. As these patients are at higher risk of conversion to dementia, we propose that an increased serum IL-1 beta level is a stage marker of the ongoing brain neurodegeneration in the continuum between normal ageing and AD. Copyright (C) 2009 S. Karger AG, Basel

Antibody Response from Whole-Cell Pertussis Vaccine Immunized Brazilian Children against Different Strains of Bordetella pertussis

Bordetella pertussis is a gram-negative bacillus that causes the highly contagious disease known as pertussis or whooping cough. Antibody response in children may vary depending on the vaccination schedule and the product used. In this study, we have analyzed the antibody response of cellular pertussis vaccinated children against B. pertussis strains and their virulence factors, such as pertussis toxin, pertactin, and filamentous hemagglutinin. After the completion of the immunization process, according to the Brazilian vaccination program, children serum samples were collected at different periods of time, and tested for the presence of specific antibodies and antigenic cross-reactivity. Results obtained show that children immunized with three doses of the Brazilian whole-cell pertussis vaccine present high levels of serum antibodies capable of recognizing the majority of the components present in vaccinal and non-vaccinal B. pertussis strains and their virulence factors for at least 2 years after the completion of the immunization procedure.