Serum homocysteine level is higher in Behçet’s disease with vascular involvement

Objective Behçets disease (BD) is a multisystemic inflammatory disorder of unknown etiology that is sometimes associated with thrombosis. However, the mechanism of hypercoagulability is not known. In this study, we investigated whether hyperhomocysteinemia, being a well-known risk factor for thrombosis, is also a contributing risk factor to venous and arterial thromboses of BD.Methods Forty-five patients with BD and 40 healthy subjects were included in the study. Sixteen patients had vascular involvement. Serum homocysteine levels were determined by fluorescence polarization immunoassay.Results In male patients, the frequency of vascular involvement was significantly higher than in females (46.7% vs 13.3%, P<0.05). Serum homocysteine levels were significantly higher in patients with BD than healthy controls (P<0.01), in patients with vascular involvement than those with mucocutaneous involvement (P<0.01) and healthy controls (P=0.001), and in male patients than in female patients (P<0.001). There was no significant difference in homocysteine levels between the BD patients with mucocutaneous involvement and healthy subjects. In multiple regression analysis, serum homocysteine level was independently associated with thrombosis (odds ratio 1.29, P<0.01), but male sex was not.Conclusions This preliminary study suggests that elevated serum homocysteine levels may play some role in the development of venous and arterial thromboses in BD.     

Effects on infarct size of reperfusion and pretreatment with β-blockade and calcium antagonists

Summary The mass of tissue at risk and the myocardial infarct developed was studied in dogs subjected to either 24-h occlusion of the left anterior descending coronary artery or 2-h occlusion followed by 22-h reperfusion. The mass of tissue at risk was defined under anaesthesia at the time of occlusion using the microsphere technique. Twenty-four hours later the hearts were removed, sliced transversely and stained with 2,3,5-triphenyltetrazolium chloride to define the infarcted tissue. All myocardial tissue was mapped and cut into small pieces for weighing and radioactive counting. Radioactivity was present in all tissue, including the infarct. In the centre of the the infarct, counts remained low and then increased very rapidly with distance just beyond the edge. Tissue at risk from infarction was taken as that with less than 15% of the peak left ventricular (non-ischaemic) counts.A linear relationship was found between the mass of the left ventricular infarct and the left ventricular mass of tissue at risk. The effect of 22 hours reperfusion was examined by this method and expressed by a regression equation. There was a significant decrease in slope for the regression line of the reperfusion data, (p<0.05, analysis of covariance), indicating less infarcted tissue for each gram of underperfused tissue.None of the drug pretreatments explored had any effect on infarct size in the 24-h occlusion model. With reperfusion, propranolol and flunarizine diminished infarct size compared with reperfusion only (p <0.05 for reduced slope, the new slope being not significantly different from zero). The effect of diltiazem was not so marked. Thus infarct size can be reduced with pretreatment, as long as the myocardium is reperfused.S. Torr and M. Main were supported by grants from the Science and Engineering Research Council, UK; A.J. Drake-Holland was supported by a fellowship from the Janssen Research Foundation.M.I.M. Noble is supported by the Garfield Weston Trust as the Weston Professor of Cardiovascular Medicine.     

Quantification of Inflammatory Mediators in Stool Samples of Patients with Inflammatory Bowel Disorders and Controls

Previous studies indicated that eosinophils andmast cells accumulate and become activated ininflammatory bowel disorders. The aim of the study wasto examine the presence of eosinophil and mast cellmediators in human stool samples of patients withinflammatory bowel disorders. We measured eosinophilcationic protein (ECP), eosinophil protein ×(EPX), methylhistamine, and₁-antitrypsin in fecal samples of 136 patients (62 Crohn's 1 disease, 24ulcerative colitis, 15 intestinal food allergy, 35 othergastrointestinal diseases) and 8 healthy controls. Wefound strongly elevated levels of ECP (median: 29,range: 0.4-1783 ng/g feces) and EPX (803, 10-33,225ng/g) in all patient groups compared to controls (ECP:1.5, 0.5-55 ng/g; EPX: 235, 12-746 ng/g). Similarresults, albeit less pronounced, were obtained formethylhistamine and alpha1-antitrypsin. Particularly highconcentrations of ECP and EPX were found in patientswith active mucosal inflammation. In conclusion, thestudy presents an easy and reliable method for thedetection of fecal ECP, EPX, and methylhistamine and mayprovide a tool to gain insight into the pathogenesis ofinflammatory bowel diseases and have potential asdiagnostic test.     

Thiamine-dependent enzyme changes in temporal cortex of patients with Alzheimer's disease

Activites of thiamine-dependent enzymes [pyruvate dehydrogenase (PDHC), -ketoglutarate dehydrogenase (KGDH), and transketolase (TK)] were measured in autopsied samples of temporal cortex from six patients with Alzheimer's disease and from eight age-matched control subjects who were free from neurological or psychiatric diseases. Times from death to freezing of dissected material at –70°C were matched. Significant decreases in PDHC (decreased by 70%;P<0.01), KGDH (decreased by 70%; p<0.01), and TK (decreased by 52%;P<0.01) were observed in brain tissue from patients with Alzheimer's disease. In contrast, activities of glutamate dehydrogenase were within normal limits. These findings suggest a possible role for alterations of brain thiamine metabolism or utilization in Alzheimer's disease     

WebBioBank: A new platform for integrating clinical forms and shared neurosignal analyses to support multi-centre studies in Parkinson’s Disease

BackgroundThe web-based systems available for multi-centre clinical trials do not combine clinical data collection (Electronic Health Records, EHRs) with signal processing storage and analysis tools. However, in pathophysiological research, the correlation between clinical data and signals is crucial for uncovering the underlying neurophysiological mechanisms. A specific example is the investigation of the mechanisms of action for Deep Brain Stimulation (DBS) used for Parkinson’s Disease (PD); the neurosignals recorded from the DBS target structure and clinical data must be investigated.ObjectiveThe aim of this study is the development and testing of a new system dedicated to a multi-centre study of Parkinson’s Disease that integrates biosignal analysis tools and data collection in a shared and secure environment.MethodsWe designed a web-based platform (WebBioBank) for managing the clinical data and biosignals of PD patients treated with DBS in different clinical research centres. Homogeneous data collection was ensured in the different centres (Operative Units, OUs). The anonymity of the data was preserved using unique identifiers associated with patients (ID BAC). The patients’ personal details and their equivalent ID BACs were archived inside the corresponding OU and were not uploaded on the web-based platform; data sharing occurred using the ID BACs. The system allowed researchers to upload different signal processing functions (in a .dll extension) onto the web-based platform and to combine them to define dedicated algorithms.ResultsFour clinical research centres used WebBioBank for 1 year. The clinical data from 58 patients treated using DBS were managed, and 186 biosignals were uploaded and classified into 4 categories based on the treatment (pharmacological and/or electrical). The user’s satisfaction mean score exceeded the satisfaction threshold.ConclusionsWebBioBank enabled anonymous data sharing for a clinical study conducted at multiple centres and demonstrated the capabilities of the signal processing chain configuration as well as its effectiveness and efficiency for integrating the neurophysiological results with clinical data in multi-centre studies, which will allow the future collection of homogeneous data in large cohorts of patients.     

SUN11602, a Novel Aniline Compound,Mimics the Neuroprotective Mechanisms of Basic Fibroblast Growth Factor

{"type":"entrez-protein","attrs":{"text":"SUN11602","term_id":"1436829565"}}SUN11602) mimics the neuroprotective effects of bFGF, and thus, we examined how {"type":"entrez-protein","attrs":{"text":"SUN11602","term_id":"1436829565"}}SUN11602 exerts its actions on neurons in toxic conditions of glutamate. In primary cultures of rat cerebrocortical neurons, {"type":"entrez-protein","attrs":{"text":"SUN11602","term_id":"1436829565"}}SUN11602 and bFGF prevented glutamate-induced neuronal death. This neuroprotection, which occurred in association with the augmented phosphorylation of the bFGF receptor-1 (FGFR-1) and the extracellular signal-regulated kinase-1/2 (ERK-1/2), was abolished by pretreatment with PD166866 (a FGFR-1 tyrosine kinase-specific inhibitor) and PD98059 (a mitogen-activated protein kinase [MAPK]/[ERK-1/2] kinase [MEK] inhibitor). In addition, {"type":"entrez-protein","attrs":{"text":"SUN11602","term_id":"1436829565"}}SUN11602 and bFGF increased the levels of CALB1 gene expression in cerebrocortical neurons. Whether this neuroprotection was linked to Calb was investigated with primary cultures of cerebrocortical neurons from homozygous knockout (Calb^–/–) and wild-type (WT) mice. In WT mice, {"type":"entrez-protein","attrs":{"text":"SUN11602","term_id":"1436829565"}}SUN11602 and bFGF increased the levels of newly synthesized Calb in cerebrocortical neurons and suppressed the glutamate-induced rise in intracellular Ca²⁺. This Ca²⁺-capturing ability of Calb allowed the neurons to survive severe toxic conditions of glutamate. In contrast, Calb levels remained unchanged in Calb^–/– mice after exposure to {"type":"entrez-protein","attrs":{"text":"SUN11602","term_id":"1436829565"}}SUN11602 or bFGF, and due to a loss of function of the gene, these neurons were no longer resistant to toxic conditions of glutamate. These findings indicated that {"type":"entrez-protein","attrs":{"text":"SUN11602","term_id":"1436829565"}}SUN11602 activated a number of cellular molecules (FGFR-1, MEK/ERK intermediates, and Calb) and consequently contributed to intracellular Ca²⁺ homeostasis as observed in the case of bFGF.