Use of acute-phase proteins (APPs) for assessment of health and disease in animals has increased greatly within the last decade. The objective was to determine the normal concentration of APPs in the serum and cerebrospinalfluid (CSF) of healthy cattle by polyacrylamide gel electrophoresis. Fifty crossbred animals (350±70kg of BW and 18±1.2 months of age), 25 heifers and 25 steers were used. CSF samples were collected from atlanto-occipital (AO) site and blood samples were obtained from the jugular vein. CSF and serum protein electrophoresis were performed by means of sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Thirty-seven proteins with molecular weights ranging from 7 and 37kDa were identified in CSF of all animals. These eight were nominally identified with immunoglobulin A and G, celuloplasmin, transferrin, albumin, α 1 -antitripsin, acidic glycoprotein, and haptoglobin.
Patients with consciousness impairment are frequently seen in the emergency room. In this setting, a detailed medical history, concerning mode of onset, previous diseases, associated symptoms, history of medications, drug exposure or abuse is essential, but not ever obtainable. So, the diagnosis may become based upon physical examination and sometimes extensive laboratorial and image tests, such as computed tomography (CT) scan, electroencephalogram and cerebrospinalfluid (CSF) examination.
The aim of this study was to determine whether the improvement of cerebrospinalfluid (CSF) flow dynamics by CSF shunting, can suppress the oligomerization of amyloid β-pep- tide (Aβ), by measuring the levels of Alzheimer’s disease (AD)-related proteins in the CSF before and after lumboperitoneal shunting. Lumbar CSF from 32 patients with idiopathic normal pressure hydrocephalus (iNPH) (samples were obtained before and 1 year after shunting), 15 patients with AD, and 12 normal controls was analyzed for AD-related proteins and APLP1-derived Aβ-like peptides (APL1β) (a surrogate marker for Aβ). We found that before shunting, individuals with iNPH had significantly lower levels of soluble amyloid pre- cursor proteins (sAPP) and Aβ38 compared to patients with AD and normal controls. We di- vided the patients with iNPH into patients with favorable (improvement 1 on the modified Rankin Scale) and unfavorable (no improvement on the modified Rankin Scale) outcomes. Compared to the unfavorable outcome group, the favorable outcome group showed signifi- cant increases in Aβ38, 40, 42, and phosphorylated-tau levels after shunting. In contrast, there were no significant changes in the levels of APL1β25, 27, and 28 after shunting. After shunting, we observed positive correlations between sAPPα and sAPPβ, Aβ38 and 42, and APL1β25 and 28, with shifts from sAPPβ to sAPPα, from APL1β28 to 25, and from Aβ42 to 38 in all patients with iNPH. Our results suggest that Aβ production remained unchanged by the shunt procedure because the levels of sAPP and APL1β were unchanged. Moreover, the shift of Aβ from oligomer to monomer due to the shift of Aβ42 (easy to aggregate) to Aβ38 (difficult to aggregate), and the improvement of interstitial-fluid flow, could lead to in- creased Aβ levels in the CSF. Our findings suggest that the shunting procedure can delay intracerebral deposition of Aβ in patients with iNPH.
Despite the high lethality rate, natural and experimental BoHV-5 infections have shown that the disease is not always lethal (Elias et al., 2004; Rissi et al., 2006; Spilki et al., 2006). Auxiliary methods for ante-mortem diagnosis of BoHV-5 infection, such as blood cell count and cerebrospinalfluid (CSF) analysis, are particularly important in animals presenting discrete and transitory dysfunctions. In addition, the results of these tests can lead to a preliminary differential diagnosis among other causes of encephalopathy in cattle.
tigens or antibodies in different assays such as enzyme-linked immunosorbent assay (ELISA) competition (14), immunora- diometric assay (10), immunoelectrophoresis-immunodiffusion (15), counterimmunoelectrophoresis (32), passive hemaggluti- nation inhibition (20), inverted linear immunoelectrophoresis (19), and immunoblotting (26). Gome´z et al. (16) were the first investigators to use monoclonal antibodies for the detection of an 87-kDa circulating antigen in PCM with 80.4% sensitivity. Since gp43 represents the most important antigen of the P. brasiliensis system and elicits antibodies that are useful both for diagnosis and for monitoring patients undergoing treatment, we report here the standardization of an alternative inhibition- ELISA (inh-ELISA) for the detection of specific gp43 antigen in serum, cerebrospinalfluid (CSF) and bronchoalveolar la- vage (BAL) fluid using a monoclonal anti-gp43 antibody.
In two recent studies, we investigated the applicability of cerebrospinalfluid (CSF) biomark- ers to study neurodegenerative processes in bipolar disorder [15, 16]. We found decreased con- centrations of the soluble forms amyloid precursor protein (APP)—sAPPα and sAPPβ - and higher ratios of amyloid β (Aβ) 42/40 and Aβ42/38 in persons with bipolar disorder compared with healthy controls . The physiological role of APP is not fully understood, but it has been linked to synaptic formation and repair as well as axonal regeneration . APP has also been suggested to be important for neural connectivity, plasticity, and activity, as well as for memory functions. We found no group difference between bipolar disorder patients and con- trols with respect to total or phosphorylated tau (T-tau/P-tau) that reflect axonal damage and neurofibrillary degeneration , or Aβ1–42 that indicate plaque deposition . In the subse- quent study, however, we found higher mean CSF concentrations of neurofilament light chain protein (NFL) in persons with bipolar disorder compared to controls . NFL is a cytoskeletal constituent of intermediate filaments. Increased CSF NFL is considered to reflect neuronal and axonal degeneration and loss . Taken together, these previous studies suggested that altered APP metabolism and axonal injury might occur in bipolar disorder.
Visceral leishmaniasis in Brazil is caused by Leishmania (Leishma- nia) chagasi and the dog is its most important reservoir. The clinical features in dogs include loss of weight, lymphadenopathy, renal failure, skin lesions, fever, hypergammaglobulinemia, hepatospleno- megaly, anemia, and, rarely, neurological symptoms. Most infected animals develop active disease, characterized by high anti-leishmania antibody titers and depressed lymphoproliferative ability. Antibody production is not primarily important for protection but might be involved in the pathogenesis of tissue lesions. An ELISA test was used to determine if there is an association between neurological symptoms and the presence of anti-L. chagasi antibodies in cerebrospinalfluid (CSF). Thirty serum and CSF samples from symptomatic mixed breed dogs (three with neurological symptoms) from a region of high incidence of visceral leishmaniasis in Brazil were examined for anti- body using total parasite antigen and anti-dog IgG peroxidase conju- gate. A high level of L. chagasi antibodies was observed in sera (mean absorbance ± SD, 1.939 ± 0.405; negative control, N = 20, 0.154 ± 0.074) and CSF (1.571 ± 0.532; negative control, N = 10, 0.0195 ± 0.040) from all animals studied. This observation suggests that L. chagasi can cause breakdown of filtration barriers and the transfer of antibodies and antigens from the blood to the CSF compartment. No correlation was observed between antibody titer in CSF and neuro- logical symptoms.
Abstract We reviewed the cerebrospinalfluid (CSF) syndromes of 100 consecutive HIV-positive patients presenting acute consciousness compromise in emergency rooms, and correlated them with clinical data. The most frequent CSF syndromes were: absolute protein-cytological dissociation (21), viral (19), neurocryptococcosis (7), relative protein-cytological dissociation (6) and septic (4), moderate hypoglycorrachia (4), severe hypoglycorrachia (4) and hydroelectrolytic disturbance (3). One fifth of the patients had CSF syndromes considered sufficient for diagnosis or an immediate clinical decision. The most common clinical data were infective and neurological. There was little correlation between the clinical data and the CSF syndromes. We conclude that in HIV-positive individuals presenting acute consciousness disturbances there are frequently non-specific results in the CSF analysis that must be weighed against a detailed history and thorough physical examination. Taking this into account, in about one fifth of cases the CSF analysis can offer useful information for treatment.
Proposed mechanisms behind IIH include brain parenchymal edema, increased cerebral blood volume, excessive CSF production, venous outflow obstruction and compromised CSF resorption. In recent years, more details about epidemiology and phenotypical presentation have been published along with a proposal of possible contribution of inflammatory factors [13–21]. For a review on analyses of CSF composition in patients with IIH, see Baykan . In this study we investigated the possibility of excess CSF production. It has been shown that overweight is associated with changes in protein composition of the cerebrospinalfluid (CSF), as some proteins were shown to be differentially expressed in the CSF of overweight patients . Thus CSF composition might be changed in patients with IIH. As various CSF compo- nents, such as sodium and proteins, are osmotically active, an altered CSF composition would be indicated by changes in CSF osmolality. It is an emerging hypothesis that derangements of the hypothalamic-pituitary-adrenal axis may lead to the development of elevated ICP in IIH via activation of mineralocorticoid receptors in the choroid plexus epithelial cells and subse- quent increase of CSF secretion into the ventricles [15, 23, 24]. Fat is an active endocrine tissue that secretes mineralocorticoid-releasing factors, providing a possible link to elevated ICP in overweight patients by an alteration of the renin-aldosterone axis and subsequent increased secretion of sodium into the CSF. In addition increased body height might be associated with higher CSF pressure, although the underlying mechanisms are unknown .
The clinical manifestations of neurocysticercosis (NC) are varied and depend on the number and location of cysts, as well as on the host immune response. Symptoms usually occur in NC when cysticerci enter a degenerative course associated with an inflammatory response. The expression of brain damage markers may be expected to increase during this phase. S100B is a calcium-binding protein produced and released predominantly by astrocytes that has been used as a marker of reactive gliosis and astrocytic death in many pathological conditions. The aim of the present study was to investigate the levels of S100B in patients in different phases of NC evolution. Cerebrospinalfluid and serum S100B concentrations were measured in 25 patients with NC: 14 patients with degenerative cysts (D), 8 patients with viable cysts (V) and 3 patients with inactive cysts. All NC patients, except 1, had five or less cysts. In most of them, symptoms had been present for at least 1 month before sample collection. Samples from 8 normal controls (C) were also assayed. The albumin quotient was used to estimate the blood-brain barrier permeability. There were no signifi- cant differences in serum (P = 0.5) or cerebrospinalfluid (P = 0.91) S100B levels among the V, D, and C groups. These findings suggest that parenchymal changes associated with a relatively small number of degenerating cysts probably have a negligible impact on glial tissue.
Knowledge of the entire protein content, the proteome, of normal human cerebrospinalfluid (CSF) would provide a critical standard to allow meaningful comparisons with and between neurologic and psychiatric disorders. CSF contains both cellular and soluble components providing insights into processes occur- ring in the central nervous system (CNS). As much as 30 to 40% of CSF is formed by the extracellular fluid of the brain and spinal cord. CSF contains both normal and disease specific components, and provides an accessible liquid window into the brain. In fact, recent data suggest CSF may provide more relevant evidence for initial or propagating pathology than the brain parenchyma itself in certain neuropsychiatric diseases. Comprehensive character- ization of the normal CSF proteome would facilitate identification of disease-specific markers. Knowledge of which proteins are present, absent, or of changed concentrations may lead to
Melancholic depression is a biologically homogeneous clinical entity in which structural brain alterations have been described. Interestingly, reports of structural alterations in melancholia include volume increases in Cerebro-Spinal Fluid (CSF) spaces. However, there are no previous reports of CSF volume alterations using automated whole-brain voxel-wise approaches, as tissue classification algorithms have been traditionally regarded as less reliable for CSF segmentation. Here we aimed to assess CSF volumetric alterations in melancholic depression and their clinical correlates by means of a novel segmentation algorithm (‘new segment’, as implemented in the software Statistical Parametric Mapping-SPM8), incorporating specific features that may improve CSF segmentation. A three-dimensional Magnetic Resonance Image (MRI) was obtained from seventy patients with melancholic depression and forty healthy control subjects. Although imaging data were pre-processed with the ‘new segment’ algorithm, in order to obtain a comparison with previous segmentation approaches, tissue segmentation was also performed with the ‘unified segmentation’ approach. Melancholic patients showed a CSF volume increase in the region of the left Sylvian fissure, and a CSF volume decrease in the subarachnoid spaces surrounding medial and lateral parietal cortices. Furthermore, CSF increases in the left Sylvian fissure were negatively correlated with the reduction percentage of depressive symptoms at discharge. None of these results were replicated with the ‘unified segmentation’ approach. By contrast, between-group differences in the left Sylvian fissure were replicated with a non-automated quantification of the CSF content of this region. Left Sylvian fissure alterations reported here are in agreement with previous findings from non-automated CSF assessments, and also with other reports of gray and white matter insular alterations in depressive samples using automated approaches. The reliable characterization of CSF alterations may help in the comprehensive characterization of brain structural abnormalities in psychiatric samples and in the development of etiopathogenic hypotheses relating to the disorders.
Statistics. Experimental results are expressed as means ⫾ SE of 4 –7 individual tissues or fluid samples. To determine differences between the composition of plasma and CSF, a Student’s t-test was used. For comparison between two sets of data showing transport function, the hypothesis that two values recorded in the same tissue at 60 min after exposure to each treatment were identical was tested using a paired t-test. The same method was used for the analysis of TER data. Values were considered different at a 95% confidence level. Statistical analyses were done using SigmaStat 3.0 (SYSTAT Software).
In our study, we evaluated HIV-positive individuals who attended the São Paulo Hospital emergency room as well as patients who were admitted to the São Paulo State AIDS/STD Reference & Training Center with signs and symptoms that suggested focal brain damage. These patients underwent neuroradiological examination and were admitted to the hospital due to suspected encephalic toxoplasmosis. Fluid punction was performed soon after admission. The presumptive diagnosis of these 16 patients was then confirmed as prescribed by the Centers for Disease Control and Prevention .
A salient question is whether the CSF raltegravir concentrations are sufficient to directly inhibit local CNS HIV-1 replication. Here again, one must consider the estimated free and bound raltegravir in CSF, and the extracellular concentrations to achieve inhibition of viral replication. Furthermore, treatment of HIVE that is sustained in perivascular and parenchymal macrophages and microglia relies on the drug concentration in brain extracellular fluid surrounding these infected cells which may differ from CSF concentration. Current estimates of inhibitory concentrations depend largely on cell culture experiments using varying amounts of human or fetal serum that bind raltegravir. Published values for the IC 95 are 15.0 ng/ml (33 nM) obtained in the presence of 50%