Diagnostic and Prognostic Value of Plasma Gelsolin in Multiorgan Failure in Patients with Sepsis

AIM: The aim of this work is to investigate the clinical value of gelsolin plasma concentration in the diagnosis of sepsis and investigate the relationship between gelsolin plasma concentration and the severity of organ dysfunction assessed by the acute physiology and chronic health evaluation (APACHE II) and SOFA scores, and to study the mortality predictive power of gelsolin plasma concentration. METHODS: We analyzed data of patients admitted with sepsis (n = 46) for 5 days. Age- and sex-matched non-specific intensive care unit (ICU) patients (n = 18) served as controls. Septic patients were then divided according to severity of disease to patients with sepsis, severe sepsis, and septic shock. Besides plasma gelsolin (pGSN) classical laboratory parameters and clinical scores (APACHE II and SOFA) were also assessed. RESULTS: Septic patients showed significantly decreased 1st-day GSN levels (170.9 ± 74.3 mg/l) compared to non-septic critically ill patients (225.9 ± 84.5 mg/l, p < 0.05). Furthermore, patients with septic shock had lower gelsolin plasma concentration than with severe sepsis and with sepsis (p < 0.05); furthermore, non-survivors had significantly lower GSN levels compared to survivors (p < 0.05). Septic patients had higher APACHE II and SOFA scores. Lower GSN level was significantly correlated with the development of multiple organ dysfunction syndrome and fatal outcome, also, patients with lower GSN level had longer ICU stay, APACHE II, and SOFA scores. APACHE II score has shown best ability to predict mortality with AUC 0.913 followed by PCT with AUC 0.828. pGSN was the least in the ability to predict mortality with AUC only 0.378 despite significant difference between pGSN levels between survivals and non-survivals. CONCLUSIONS: pGSN might serve as efficient complementary marker in sepsis. However, the prognostic role of pGSN in mortality requires further investigation in larger studies

Vitamin C attenuates the toxic effect of nutmeg on primary visual occipital cortex in rats

Background: Nutmeg is neurotoxic in rats and possibly neurotoxic also in hu- mans. The aim of this study is to investigate the effect of nutmeg on the primary visual occipital cortex of adult male rat and to evaluate the possible protective role of vitamin C.  Materials and methods: Fifty Sprague-Dawley adults male rats were randomly divided into three main groups; control, nutmeg-treated (500 and 1000 mg/kg/ /day) and protected groups (nutmeg + vitamin C [500 mg/kg/day]). All rats were treated orally by gavage for 5 days per week for 6 weeks. At the end of the experiment, primary visual occipital cerebral cortex was subjected to histological, immunohistochemical and genetic analyses.  Results: Our results revealed toxic effects of nutmeg on the primary visual occipital cerebral cortex in adult male albino rat. This was indicated by histopathological alterations, including pyknotic nuclei surrounded with vacuolations by light micro- scopic studies and degenerations of organelles by electron microscopic studies. In addition, we detected an increase in immunoreactivity for GFAP and caspase-3 by immunohistochemical assessments. Apoptotic bands appeared in genetic studies. Co-administration of vitamin C ameliorated nutmeg-induced toxic alterations on the primary visual occipital cerebral cortex.  Conclusions: Nutmeg administration caused histopathological and genetic changes in the primary visual occipital cerebral cortex in adult male albino rats. These changes were improved by co-administration of vitamin C.

Transplantation of bone marrow-derived mesenchymal stem cells ameliorated dopamine system impairment in a D-galactose-induced brain ageing in rats

Ageing is the primary risk factor for Parkinson's disease. Progressive motor and coordination decline that occurs with ageing has been linked to nigrostriatal dysfunction. Few studies have investigated the efficacy of mesenchymal stem cells in ameliorating the structural and functional alterations in the ageing nigrostriatal system. This study is the first to evaluate the effects of intravenous injection of bone marrow-derived mesenchymal stem cells (BMMSCs) in a D-galactose-induced rat model of nigrostriatal ageing. BMMSCs were intravenously injected once every 2 weeks for 8 weeks. The transplanted cells survived, migrated to the brain, and differentiated into dopaminergic neurones and astrocytes. BMMSC transplantation improved locomotor activity, restored dopaminergic system function, preserved atrophic dopaminergic neurones in the substantia nigra, exerted antioxidative effects, and restored neurotrophic factors. Our findings demonstrate the efficacy of BMMSC injection in a nigrostriatal ageing rat model, and suggest that these cells may provide an effective therapeutic approach for the ageing nigrostriatal system

Correlations of behavioral deficits with brain pathology assessed through longitudinal MRI and histopathology in the R6/1 mouse model of huntington's disease

Huntington's disease (HD) is caused by the expansion of a CAG repeat in the huntingtin (HTT) gene. The R6 mouse models of HD express a mutant version of exon 1 HTT and typically develop motor and cognitive impairments, a widespread huntingtin (HTT) aggregate pathology and brain atrophy. Unlike the more commonly used R6/2 mouse line, R6/1 mice have fewer CAG repeats and, subsequently, a less rapid pathological decline. Compared to the R6/2 line, fewer descriptions of the progressive pathologies exhibited by R6/1 mice exist. The association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood in many models of HD. In attempt to link these factors in the R6/1 mouse line, we have performed detailed assessments of behavior and of regional brain abnormalities determined through longitudinal, in vivo magnetic resonance imaging (MRI), as well as an end-stage, ex vivo MRI study and histological assessment. We found progressive decline in both motor and non-motor related behavioral tasks in R6/1 mice, first evident at 11 weeks of age. Regional brain volumes were generally unaffected at 9 weeks, but by 17 weeks there was significant grey matter atrophy. This age-related brain volume loss was validated using a more precise, semi-automated Tensor Based morphometry assessment. As well as these clear progressive phenotypes, mutant HTT (mHTT) protein, the hallmark of HD molecular pathology, was widely distributed throughout the R6/1 brain and was accompanied by neuronal loss. Despite these seemingly concomitant, robust pathological phenotypes, there appeared to be little correlation between the three main outcome measures: behavioral performance, MRI-detected brain atrophy and histopathology. In conclusion, R6/1 mice exhibit many features of HD, but the underlying mechanisms driving these clear behavioral disturbances and the brain volume loss, still remain unclear. © 2013 Rattray et al

Risks for public health related to the presence of furan and methylfurans in food

EFSA wishes to thank the hearing experts: Diana Doell and Ruud Woutersen and EFSA staff member: José Cortinas Abrahantes for the support provided to this scientific output. The CONTAM Panel acknowledges all European competent institutions and other stakeholders that provided occurrence data on furan and methylfurans in food, and supported the data collection for the Comprehensive European Food Consumption Database. Adopted: 20 September 2017Peer reviewedPublisher PD

Prognostic value of IL6 in young adults presenting with acute coronary syndrome

Background: Interest to evaluate the prognostic value of the inflammatory marker, IL-6 in young patients with ACS. Methods: 140 young patients (18–40 years old) with ACS, were included in this non-randomized prospective study. They were subjected to (a) full clinical evaluation (b) Laboratory evaluation (c) Standard 12 leads ECG and Echocardiography and (d) coronary angiography. The patients were divided into two groups, those with acute chest pain and positive coronary angiography (110 patients), and those with acute chest pain but with normal coronary angiography (control group, 30 patients). Results: The IL-6 level was significantly higher in patients with documented CAD compared to the control group (39.56 ± 2.5 Vs 3.83 ± 0.79 P < 0.001). IL-6 level was significantly higher in patients with significant lesions who needed to perform PCI (92 patients) than patients with non-significant atherosclerotic plaques needing just medical treatment (18 patients) (45.5 ± 23.17 Vs 9.22 ± 1.93 P < 0.001). Higher level of IL-6 in STEMI patients (63 Patients 57%) than NSTEMI (23 Patients 21%) and UA (24 Patients 22%) (49.56 ± 23 Vs 43.5 ± 17 Vs 9.5 ± 2.53 respectively with P < 0.001) was observed. The optimal cutoff value for IL-6 level to predict morbidity was 41 pg/ml with a sensitivity of 100%, specificity of 66%, and positive predictive value of 25%, negative predictive value of 100% and the diagnostic accuracy of 69%. Conclusion: The use of IL-6 as a prognostic marker for ACS may be of Value; it may predict the severity of CAD as well as the mortality and morbidity of young patients with acute coronary syndrome

Short-term effect of percutaneous coronary intervention on ischemic mitral regurgitation

Background: The effect of revascularization by PCI for acute coronary syndrome (ACS) on the severity of ischemic mitral regurge (IMR) is still unclear. Objective: To evaluate the effect of successful total revascularization by PCI for ACS on the degree of IMR. Methods: A total of 240 patients presenting with ACS for the first time were studied by this an open-label, multicenter, prospective clinical trial between July 2015 to February 2017. All patients were subjected for clinical assessment, transthoracic echocardiographic assessment and coronary angiography. The patients divided into two groups: group A; those who had undergone successful total revascularization of a significant coronary artery disease using PCI, and group B; those who had optimal medical treatment with no total revascularization, failed PCI or for CABG. Group A patients subdivided into subgroup I, patients with improvement of the IMR; and subgroup II, patients with no improvement of IMR. Results: Only 65% of the patients showed IMR and 149 of them underwent successful complete revascularization by PCI; 68% of them showed IMR improvement and 32% showed no improvement. There was a significant improvement of the IMR degree after total revascularization by PCI. Moreover, this improvement was significant in subgroup I (p < 0.001). Percutaneous coronary intervention, EF and SWMI were significant predictors of IMR improvement following successful complete revascularization. Conclusion: Successful total revascularization by early PCI improve IMR degree. Keywords: Ischemic mitral regurge, Total revascularization, Acute coronary syndrome, Percutaneous coronary intervention, Myocardial infarction, Echocardiograph