finding of massively elevated GFAP blood values, within minutes after symptom onset in ICH and traumatic brain injury, re- spectively. In ICH, a strong correlation exists between ICH volume and GFAP plasma values, further underlining the above- mentioned ‘‘mechanic’’ hypothesis. [3,4] In the BE FAST trial, GFAP values of more than 100 mg/l were found in acute ICH patientswith a mean of 29 mg/l, which is vastly higher than even the patientswith the highest GFAP values in the present study.  In traumatic brain injury, the magnitude of GFAP elevation is strongly correlated to clinical severity and extent of the brain lesion. Values.7 mg/l were associated with an unfavorable outcome, while values.15 mg/l were not survived. [12–14] Three studies in the literature point to increased GFAP levelsin plasma ofpatientswith malignant glioma (glioblastoma) but not in metastasis, and suggest a potential use of this marker in the differential diagnosis ofpatientswith newly identified cerebral mass lesions. [10,11,16] Malignant glioma tend to produce large amounts of GFAP, and many of them show substantial areas of necrotic cell death. Furthermore, it is well known that the blood brain barrier is disintegrated within the tumor. Thus, a gradual release of GFAP in to the blood stream appears plausible in glioblastoma, in contrast to other brain tumors such as metastases. Apart from what was already known (i.e., elevated GFAP values in ICH, traumatic brain injury, and glioblastoma), we were not able to identify a disease or a group ofdiseasesin our widespread explorative study that was consistently associated with increased blood GFAP levels. However, a few individual values from different disease categories were found clearly elevated and need further consideration: One patient had a subarachnoid hemor- rhage with a concomitant parenchymal bleeding.  This explains the GFAP increase similar to what happens in intracerebral hemorrhage. All other patientswith
All statistics were computed using SPSS (IBM Corp. 2013 SPSS Statistics for Windows, version 22.0). The Shapiro-Wilk test in conjunction with inspection of histograms and the skewness statistic were used to test for normality of distribution. Age, NFL and BPF were all non-nor- mally distributed. Spearman’s rho was used for bivariate correlation testing. Partial rank corre- lations was used for non-parametric partial correlation testing. Linear regression was used to evaluate the relationship between age and NFL, GFAP and BPF. Wilcoxon signed rank test was used to test for inter-lab differences in NFL levels. An α-level of 0.05 was chosen for determina- tion of statistical significance. The Bonferroni-Holm method was applied to control for family- wise error rate in the significance testing of the partial correlations. One individual (specified in Fig 1) was excluded from correlation testing and regression line estimation regarding NFL on the basis of having an outlier NFL value and no other individuals of the same age was avail- able for comparison.
The mammalian brain contains two main groups of cells: the neurons and the neuroglia. Until recently the neuroglia were considered to play only a minor role in brain function, serving merely as a physical framework of support for neurons (the so-called “nerve glue” of Virchow, see Ref. 1). This concept has changed dramatically in the past decade: neuroglia are now recognized as partners with neurons in normal and abnormal brain func- tion (2,3). The neuroglia belong to three main subdivisions: the oligodendrocytes, whose main function is to provide the myelin which insulates the neuronal axons; a morphologi- cally and biochemically heterogeneous group known as the astrocytes, and the microglia which are the immune cells of the brain. Of these 3 groups the astrocytes are the most numerous and interact functionally with neu- rons. Astrocyte processes envelop synaptic structures forming “perineuronal nets” (4,5), while other processes make intimate contact with the blood capillaries through specialized structures known as “end feet”. Thus, astro- cytes provide a conduit for the transport of energy from the blood stream to the nerve terminals and recent work has demonstrated a tight coupling between synaptic activity and the uptake of glucose by the astrocytic “end feet” (6). Interestingly, astrocytes first me- tabolize glucose to lactate before supplying it as energy to neurons. Further astrocytes modulate the transmission of synaptic signals by the uptake of K + and neurotransmitters (7-
Spinal astrocyte activation contributes to the pathogenesis of paclitaxel-induced neuropathic pain (PINP) in animal models. We examined glialfibrillaryacidicprotein (GFAP; an astrocyte marker) immunoreactivity and gene expression of GFAP, glutamate transporters and receptor subunits by real time PCR in the anterior cingulate cortex (ACC) at 7 days post first administration of paclitaxel, a time point when mice had developed thermal hyperalgesia. The ACC, an area in the brain involved in pain perception and modulation, was chosen because changes in this area might contribute to the pathophysiology of PINP. GFAP transcripts levels were elevated by more than fivefold and GFAP immunoreactivity increased in the ACC of paclitaxel-treated mice. The 6 glutamate transporters (GLAST, GLT-1 EAAC1, EAAT4, VGLUT-1 and VGLUT-2) quantified were not significantly altered by paclitaxel treatment. Of the 12 ionotropic glutamate receptor subunits transcripts analysed 6 (GLuA1, GLuA3, GLuK2, GLuK3, GLuK5 and GLuN1) were significantly up-regulated, whereas GLuA2, GLuK1, GLuK4, GLuN2A and GLuN2B were not significantly altered and GLuA4 was lowly expressed. Amongst the 8 metabotropic receptor subunits analysed only mGLuR8 was significantly elevated. In conclusion, during PINP there is astrocyte activation, with no change in glutamate transporter expression and differential up-regulation of glutamate receptor subunits in the ACC. Thus, targeting astrocyte activation and the glutamatergic system might be another therapeutic avenue for management of PINP.
Rheumatoid arthritis (RA) is a chronic, autoimmune and inflammatory joint disease with a poorly understood etiology. Despite widespread diagnostic use of anti-citrullinated protein antibodies and rheumatoid factor proteins there is a strong demand for novel serological biomarkers to improve the diagnosis this disease. The present study was aimed to identify novel autoantigens involved in rheumatoid arthritis (RA) pathogenesis through immune-proteomic strategy. Synovial fluid samples from clinically diagnosed RA patients were separated on two-dimensional gel electrophoresis (2-DE). Samples from patientswith non-RA rheumatisms (osteoarthritis and trauma) were used as controls. Immunoreactive proteins were spotted by Western blotting followed by identification through Q-TOF mass spectrometer analysis. Forty Western blots were generated using plasma from ten individual RA patients and 33 reactive spots were identified, 20 from the high molecular weight (HMW) gel and 13 from the low molecular weight (LMW) gel. Among the 33 common immunogenic spots, 18 distinct autoantigens were identified, out of which 14 are novel proteins in this context. Expression analysis of five important proteins, vimentin, gelsolin, alpha 2 HS glycoprotein (AHSG), glialfibrillaryacidicprotein (GFAP), and a1B- glycoprotein (A1BG) by Western blot analysis using their specific antibodies revealed their higher expression in RA synovial fluid as compared to non-RA samples. Recombinantly expressed GFAP and A1BG protein were used to develop an in-house ELISA to quantify the amount of autoantibodies in the RA patients. RA patients revealed an increase in the expression of GFAP and A1BG in the plasma as compared to osteoarthritis patients. Therefore, GFAP and A1BG can be proposed as potential new autoantigens of diagnostic importance for RA subjects. Further characterization of these proteins in rheumatoid arthritis will be helpful in understanding the role of these proteins in the disease pathogenesis providing new diagnostic tool with better specificity and accurate detection of the disease.
Brain magnetic resonance imaging after the cardiac arrest showed only old ischemic areas compatible with her previous strokes (Figure 1). A computerized tomography angiography revealed severe stenosis of the left cervical internal carotid artery and occlusion of the right cervical internal carotid artery (Figure 2). TCD showed symmetric but decreased blood
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the human central nervous system. Although its etiology is unknown, the accumulation and activation of mononuclear cells in the central nervous system are crucial to its pathogenesis. Chemokines have been proposed to play a major role in the recruitment and activation of leukocytes in inflammatory sites. They are divided into subfamilies on the basis of the location of conserved cysteine residues. We determined the levelsof some CC and CXC chemokines in the cerebrospinal fluid (CSF) of 23 relapsing-remitting MS patients under interferon-ß-1a therapy and 16 control subjects using ELISA. MS patients were categorized as having active or stable disease. CXCL10 was significantly increased in the CSF of active MS patients (mean ± SEM, 369.5 ± 69.3 pg/mL) when compared with controls (178.5 ± 29.1 pg/mL, P < 0.05). CSF levelsof CCL2 were significantly lower in active MS (144.7 ± 14.4 pg/mL) than in controls (237.1 ± 16.4 pg/ mL, P < 0.01). There was no difference in the concentration of CCL2 and CXCL10 between patientswith stable MS and controls. CCL5 was not detectable in the CSF of most patients or controls. The qualitative and quantitative differences of chemokines in CSF during relapses of MS suggest that they may be useful as a marker of disease activity and of the mechanisms involved in the pathogenesis of the disease.
Although not the only factor responsible for cardiac involvement in acromegaly, the coexistence of high blood pressure levels worsens the effects of acromega- lic cardiomyopathy (10), as previously observed (11). There were no differences between hypertensive and normotensive acromegalic patients regarding GH and IGF-1 levels; patient with active acromegaly were less frequently hypertensive than those with cured/con- trolled disease. The presence of younger patientswith active acromegaly and older patientswith controlled acromegaly could explain this inding. However, inpatientswith active acromegaly, IGF-1 was a predictor of systolic blood pressure levels and albuminuria was a possible mediator, while inpatientswith controlled disease, other factors were associated withblood pres- sure levels, including metabolic syndrome components, such as triglycerides and abdominal obesity.
Few treatments in psychiatry were discovered and developed based on a previously developed theory. The therapeutic effects of the irst antidepressant and antipsychotic drugs, for example, were serendipitously observed before a theory on how they work was described. By contrast, convulsive therapy was developed in Budapest by Dr. Lazlo Meduna based on facts that led him to foresee its possible clini- cal utility. His experience and interest in microscopically studying glial cells and his clinical psychiatric experience led him to describe a reduction inglial density in the brains ofpatientswith schizophrenia and a rise ofglial cells in the brains ofpatientswith epilepsy. Other ideas were later added to this initial insight. However, this glial reduction was never conirmed in the brains ofpatientswith schizophrenia. 1 The theory was abandoned; however, the
this respect, it is important to recognize the potential for a central nervous system or subarachnoid space connection, and to search carefully for evidence of such a connection during diagnostic procedures and before initiating treatment. 2–4,7–9,11 Therefore, the evaluation of a congenital midline mass must always include either a computed tomography (CT) or magnetic resonance imaging (MRI) scan to rule out intracra- nial extension. MRI offers superior soft-tissue contrast, aid- ing in the planning of the surgical approach, with the additional advantage of saving the child from being exposed 1225
In conclusion, it seems that many patientswith PKU with all types of disorder severity tolerate more NP than prescribed, and in some cases the increase was at least 50%. This extra NP may positively influence a patient’s nutritional status and quality of life, as eating more natural food is likely to positively affect the general health status of the patient. It is clear that most of our patients were over-restricted in NP allowance. Therefore, it is beneficial to assess maximum NP tolerance at periodic intervals in clinical care, as different variables may affect tolerance. There is very little information on how Phe tolerance changes with increasing age, so more data is needed to clearly show how NP tolerance changes from childhood until adulthood.
A propentoilina é uma xantina que deprime a ativação das células gliais, cujas respostas contribuem para o dano neural durante inlamação. A injeção de brometo de etídio no sistema nervoso central induz a perda oligodendroglial e astrocitária, resultando em desmielinização, neuroinlamação e ruptura da barreira hematoencefálica. Os astrócitos sobreviventes apresentam vigorosa reação ao redor da lesão com aumento da imunorreatividade à proteína glial ibrilar ácida (GFAP). Objetivo: Este estudo objetivou avaliar o efeito da propentoilina sobre a resposta astrocitária após injúria gliotóxica. Método: Ratos Wistar foram injetados com brometo de etídio na cisterna basal e tratados ou não com propentoilina (12.5mg/kg/dia, intraperitoneal). Amostras do tronco encefálico foram coletadas dos 15 aos 31 dias pós-injeção do gliotóxico e processadas para estudo ultraestrutural e imuno-histoquímico para GFAP. Resultados e Conclusão: Os resultados demonstram que a propentoilina reduziu a ativação astrocitária até o 21 o dia, sugerindo que essa droga pode
Purpose: We evaluated dynamic thiol/disulfide homeostasis (TDH), malondial- dehyde (MDA) levels, and catalase (CAT ) activity inpatientswith age-related macular degeneration (AMD). All analyzes were conducted on plasma samples. Methods: Thirty-two patientswith AMD and 38 age-matched healthy con- trols were included. Native thiol, total thiol, and disulfide levels and TDH status were determined using a novel, automated assay. MDA levels and CAT activity were determined. Percentages were compared using the chi-squared test. The Student’s t-test and Mann-Whitney U-test were used to compare quantitative variables.
Objective: to estimate the mortality risk associated withblood sugar levelsinpatientswith septicemia in an Intensive Care Unit. Methods: this is a retrospective cohort study, performed with 263 patientswith septicemia admitted to an intensive care unit, using the hospital management system data. Results: there was a higher frequency ofpatients aged from 14 to 59 years old (52.1%), male (55.9%), white (85.9%) of clinical specialties (65.8%); the hospitalization period ranged from 2 to 132 days; 91.6% ofpatients (n=241) were hyperglycemic at the time of hospitalization. There were 37 (14.1%) deaths, more frequent inpatientswith hyperglycemia during hospitalization (1.49 deaths/1,000 patients). Conclusion: hyperglycemia was a risk factor for mortality inpatients admitted to the Intensive Care Unit.
correlation between mitral flow velocity and early ventricular filling in the restrictive syndromes. Perhaps with a greater number ofpatients these findings could be confirmed. In HCM, there was a good correlation with direct measurements of diastolic dysfunction and with indirect measurements such as left atrial size. In HCM, diastolic function is a marker of more severe heart failure, as indicated by the association with high NT pro-BNP levels. NT pro-BNP may be one more useful ancillary diagnostic method in the assessment and quantification of dysfunction in HCM patients.
Especially in rare and aggressive cancer types, such as ULMS, reliable prognostic parameters are of particular interest. Studies investigating clinical prognostic parameters such as tumor stage or histological grade inpatientswith ULMS have shown inconsistent results. On the one hand a report from Kapp et al. showed an independent influence of tumor stage and histologic grade on survival whereas Hoang et al. did not describe an influence of tumor grade on patient’s survival. Zivanovic et al. showed that FIGO stage does not perform well in terms of predicting overall survival (OS) inpatientswith ULMS [4–6]. C-reactive protein (CRP) is a readily available and cheap laboratory parameter, that is widely used in clinical routine as the most important acute phase serum protein to monitor infection. Besides being induced in the acute phase of inflammatory response, CRP has been shown to be elevated inpatientswith a variety of cancer types and an association with prognosis was found. In particular elevated CRP serum levels have been associated with impaired survival inpatients suffering from gynae- cologic malignancies including cervical, ovarian, and endometrial cancer [7–9]. In addition several studies investigated the clinical significance of CRP serum levelsin soft tissue sarcoma . Therefore, this study set out to evaluate whether pre-treatment CRP serum levels might be used as novel prognostic parameter inpatientswith ULMS.
Taking into account the lactate synthesis and clearance mecha- nisms, the collection site in critical patients may, theoretically, inter- fere with the interpretation of results and lead to inadequate manage- ment. Lactate measured in samples collected from arterial blood (Lart) would best represent the overall perfusion since such samples contain blood coming from the pulmonary veins, superior vena cava and infe- rior vena cava. Peripheral lactate (Lper) may preferentially relect the perfusion and metabolism of the compartment from which the blood was drawn (i.e. the local perfusion) but not the overall perfusion. On the other hand, although lactate measured inblood drawn from the superior vena cava (Lcen) is regarded as an overall measurement, it may not appropriately represent the perfusion in the lungs and gas- trointestinal tract. 8,9
Thirty-three subjects were selected and 22 who per- formed all procedures were included. Among the 11 pa- tients who were excluded, eight did not fulfill the criteria for acceptance of the sputum sample and three had broncho- spasm during induction, which prevented collection of the sputum sample. However, no clinical difference was ob- served between included and excluded patients. None of the patients had smoked actively for at least 6 months prior to the study; received inhaled or oral corticosteroids, or other systemic drugs including theophylline, antibiotics or nonsteroidal anti-inflammatory drugs, or reported any acute exacerbations for at least eight weeks prior to sputum induction.
335 patients aged 20 to 60 years with various parodontitis inflammatory diseases have been selected for research. all patients have been divided into four groups of different age: with rheumatism – 96 persons, with heart ischemic ill- ness – 82 persons, with arterial hypertension – 89 persons, with neurocirculatory dystonia – 68 persons. the presented results of supervision show diagnostic significant changes of pulp microflora with odontogenic infection inpatients, suffering cardiovascular diseases.
Krabbe disease (globoid cell leukodystrophy) is an inherited recessive autosomal leukodystrophy caused by deficiency of the enzyme galactocerebrosidase. The lack of this enzyme leads to the build-up of galactolipids that will promote the death of oligodendrocytes and the demyelination of the central and peripheral nervous systems. There are two clinical forms: early onset and late onset. This article reports a case of late onset Krabbe disease and discusses the importance of early diagnosis for its prognosis.