Sochocka M.,Polish Academy of Sciences |
Koutsouraki E.S.,Aristotelian University |
Gasiorowski K.,Wroclaw Medical University |
Leszek J.,Wrocław University
CNS and Neurological Disorders - Drug Targets | Year: 2013
Vascular and metabolic dysfunctions and mitochondrial failure are now believed to be contributors to Alzheimer's disease (AD) pathogenesis. Vascular dysfunction includes reduced cerebral blood flow (CBF), blood-brain barrier (BBB) disturbances and cerebral amyloid angiopathy (CAA). Mitochondrial failure results in deregulation of Ca2+ homeostasis and elevated reactive oxygen species (ROS) generation, both of which are linked to neurotoxicity. Increased levels of ROS stimulate proinflammatory gene transcription and release of cytokines, such as IL-1, IL-6, and TNF-α, and chemokines, thereby inducing neuroinflammation. Conversely, inflammatory reactions activate microglia and astrocytes to generate large amounts of ROS, so neuroinflammation could be perceived as a cause and a consequence of chronic oxidative stress. The interaction between oxidative stress and neuroinflammation leads to amyloid-β (Aβ) generation. The deposition of Aβ peptide in the brain generates a cascade of pathological events, including the formation of neurofibrillary tangles (NFTs), inflammatory reactions, increased oxidative stress and mitochondrial dysfunction, which are causative factors of cell death and dementia. The purpose of this paper is to provide current evidence on vascular dysfunction and mitochondrial failure, both in neurons and glia and in brain vascular wall cells in the context of potential application for treatment of AD and other neurodegenerations. © 2013 Bentham Science Publishers.
Dotsikas Y.,National and Kapodistrian University of Athens |
Markopoulou C.K.,Aristotelian University |
Koundourellis J.E.,Aristotelian University |
Loukas Y.L.,National and Kapodistrian University of Athens
Journal of Separation Science | Year: 2011
A liquid chromatography/tandem mass spectrometry (LC-MS/MS) method, characterized by complete automation and high-throughput, was developed for the determination of colistin A and B in human plasma. All sample preparation procedures were performed by using 2.2 mL 96-deep-well plates, whereas robotic liquid-handling workstations were utilized for all liquid transfer steps, including solid-phase extraction (SPE). The whole preparation procedure was very rapid, whereas the method had a very short chromatographic run time of just 2 min. Sample analysis was performed by reversed phase LC-MS/MS, with positive electrospray ionization, using multiple reaction monitoring. The absence of available purified colistin A and B standards led to the development of a novel LC method with evaporative light-scattering detector for the determination of their stoichiometries in the standard mixture, along with its purity. The proposed bioanalytical method was fully validated and it was proven to be selective, accurate, precise, reproducible and suitable for the determination of colistin A and B in human plasma. It was applied successfully to a pharmacokinetic study for the determination of both analytes in samples of patients. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Athyros V.G.,Aristotelian University |
Tziomalos K.,Aristotelian University |
Karagiannis A.,Aristotelian University |
Mikhailidis D.P.,University College London
Obesity Reviews | Year: 2011
Morbid obesity is associated with increased morbidity and represents a major healthcare problem with increasing incidence worldwide. Bariatric surgery is considered an effective option for the management of morbid obesity. We searched MEDLINE, Current Contents and the Cochrane Library for papers published on bariatric surgery in English from 1 January 1990 to 20 July 2010. We also manually checked the references of retrieved articles for any pertinent material. Bariatric surgery results in resolution of major comorbidities including type 2 diabetes mellitus, hypertension, dyslipidemia, metabolic syndrome, non-alcoholic fatty liver disease, nephropathy, left ventricular hypertrophy and obstructive sleep apnea in the majority of morbidly obese patients. Through these effects and possibly other independent mechanisms bariatric surgery appears to reduce cardiovascular morbidity and mortality. Laparoscopic Roux-en-Y gastric bypass (LRYGB) appears to be more effective than laparoscopic adjustable gastric banding (LAGB) in terms of weight loss and resolution of comorbidities. Operation-associated mortality rates after bariatric surgery are low and LAGB is safer than LRYGB. In morbidly obese patients bariatric surgery is safe and appears to reduce cardiovascular morbidity and mortality. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.
Veloukas T.,Aristotelian University |
Leroch M.,University of Kaiserslautern |
Hahn M.,University of Kaiserslautern |
Karaoglanidis G.S.,Aristotelian University
Plant Disease | Year: 2011
Botrytis cinerea isolates (n = 122) were collected from strawberry fields located in northern Greece during a 3-year period (2008-10) and tested for their sensitivity to the succinate dehydrogenase inhibitor boscalid. Sensitivity measurements showed three distinct phenotypes consisting of isolates highly sensitive (fungicide concentration causing inhibition of germ tube growth by 50% [EC 50 values] of 0.05 to 0.21 μg ml -1), moderately resistant (EC 50 values of 1.37 to 7.79 μg ml -1), or highly resistant (EC 50 values of >50 μg ml -1) to boscalid. Sequence analysis of the sdhB gene revealed five mutations leading to amino acid substitutions in the SdhB subunit in isolates moderately resistant and highly resistant to boscalid. Three moderately resistant isolates showed a nucleotide change from A to T at codon 230, resulting in an asparagine to isoleucine (N230I) substitution. Several moderately resistant isolates showed a nucleotide change from C to T at codon 272, resulting in a substitution from histidine to arginine (H272R) whereas, in another set of isolates, a nucleotide change from A to G was found at the same codon, leading to a substitution from histidine to tyrosine (H272Y). One highly resistant isolate had a nucleotide change from A to T at codon 272, leading to a substitution from histidine to leucine (H272L), whereas, in three other highly resistant isolates, a double nucleotide change from CC to TT was observed at codon 225, resulting in a substitution from proline to phenylalanine (P225F). To facilitate rapid detection of these mutations associated with resistance to boscalid, a primer-introduced restriction analysis polymerase chain reaction was developed. The method was successfully applied to the moderately and highly resistant subpopulations and showed that the H272R mutation was predominant with relative frequencies of 28.5, 37.5, and 30% during 2008, 2009, and 2010, respectively. In contrast, the H272L mutation was detected at a frequency of 2.5% only in the 2009 population, whereas the P225F mutation was detected at a frequency of 7.5% only in the 2010 population. © 2011 The American Phytopathological Society.
Markopoulou C.K.,Aristotelian University |
Kouskoura M.G.,Aristotelian University |
Koundourellis J.E.,Aristotelian University
Journal of Separation Science | Year: 2011
Twenty-five descriptors and 61 structurally different analytes have been used on a partial least squares (PLS) to latent structure technique in order to study chromatographically their interaction mechanism on a phenyl column. According to the model, 240 different retention times of the analytes, expressed as Y variable (log k), at different % MeOH mobile-phase concentrations have been correlated with their theoretical most important structural or molecular descriptors. The goodness-of-fit was estimated by the coefficient of multiple determinations r2 (0.919), and the root mean square error of estimation (RMSEE=0.1283) values with a predictive ability (Q2) of 0.901. The model was further validated using cross-validation (CV), validated by 20 response permutations r2 (0.0, 0.0146), Q2 (0.0, -0.136) and validated by external prediction. The contribution of certain mechanism interactions between the analytes, the mobile phase and the column, proportional or counterbalancing is also studied. Trying to evaluate the influence on Y of every variable in a PLS model, VIP (variables importance in the projection) plot provides evidence that lipophilicity (expressed as Log D, Log P), polarizability, refractivity and the eluting power of the mobile phase are dominant in the retention mechanism on a phenyl column. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Tzanavaras P.D.,Aristotelian University
Current Organic Chemistry | Year: 2010
Impurity profiling of active pharmaceutical ingredients is a critical quality control parameter during all stages of the development, production and stability testing of pharmaceutical formulations. Literature on this is continuously increasing, it is therefore important to keep track on the latest achievements and applications. This review presents an overview of the most recently published results on the analysis of organic impurities in pharmaceutical samples and active ingredients. Special attention is given to the most widely used techniques, such as liquid chromatography, capillary electrophoresis and mass spectrometry. © 2010 Bentham Science Publishers Ltd.
Baloyannis S.J.,Aristotelian University
Journal of Alzheimer's Disease | Year: 2014
Alzheimer's disease (AD) is a progressive degeneration of the brain, inducing memory decline, inability in learning, and behavioral alterations, resulting progressively in a marked deterioration of all mental activities and eventually a vegetative state. The main causative factor, however, is still unclear. The implication of amyloid-β, AβPP, tau protein, the selective loss of neurons, the alteration of the synapses, the cytoskeletal changes, and the morphological alterations of the brain capillaries contribute substantially to the pathogenetic profile of the disease, without sufficiently enlightening the initial steps of the pathological procedures. The ultrastructure of the neuronal organelles as well as histochemical studies revealed substantial alterations, primarily concerning mitochondria. In this study, the morphological and morphometric alterations of the Golgi apparatus (GA) are described in the Purkinje cells of the cerebellum in twenty AD brains, studied with electron microscopy. As it is well established, GA has a very important role to play in many procedures such as glycosylation, sulfation, and proteolysis of protein systems, which are synthesized in the endoplasmic reticulum of nerve cells and glia. GA may also play a crucial role in protein trafficking and in misfolding of protein aggregates. In addition, the hyperphosphorylation of tau protein is closely related with the pathology of GA. In AD cases, described in this study, an obvious fragmentation of the cisternae of GA was observed in the Purkinje cells of the vermis and the cerebellar hemispheres. This alteration of GA may be associated with alterations of microtubules, impaired protein trafficking, and dendritic, spinal, and synaptic pathology, since protein trafficking plays an essential role in the three dimensional organization of the dendritic arbor and in the integrity of the synaptic components. © 2014 IOS Press.
Baloyannis S.J.,Aristotelian University |
Baloyannis I.S.,Aristotelian University
Journal of the Neurological Sciences | Year: 2012
Although the etiopathological background of Alzheimer's disease (AD) is mostly associated with the deposition of Αβ-peptide, the hyperphosphorylation of τ protein, the synaptic pathology and the mitochondrial alterations, the vascular factor may play substantial role in plotting the multifactorial pattern of the disease. We attempted to study the blood capillaries in the hippocampus, the acoustic, the visual and the parietal cortex in twelve early cases of Alzheimer's disease. Samples were processed for Golgi silver impregnation technique and electron microscopy. The morphological findings were compared with normal controls. The study of the brain capillaries in cases of AD, revealed numerous fusiform dilatations, tortuosities, abnormal branching and fusion, though the morphometric estimation revealed a decrease of the number of capillaries per mm3 in comparison with normal control brains. The ultrastructural study revealed mitochondrial abnormalities in the endothelial cells of a substantial number of capillaries and marked degeneration of the pericytes. Perivascular microglial proliferation was also prominent in the hippocampus and the parietal lobe. Our findings both in Golgi staining and electron microscopy plead in favor of the essential role that the microvascular alterations may play in the broad pathogenetic spectrum of AD. © 2012 Elsevier B.V.
Koutsouraki E.,Aristotelian University |
Costa V.,Aristotelian University |
Baloyannis S.,Aristotelian University
International Review of Psychiatry | Year: 2010
Multiple sclerosis (MS) is a progressive demyelinating and degenerative disease of the CNS with symptoms dependent on the type of the disease and the site of lesions. During the progression of the disease, symptoms become more permanent and progressive disability ensues. MS is a disease characterized by wide variations between patients, thus making categorization difficult. The aim of the current study was to review the existing epidemiological data of MS in Europe published during the last decade (20002009), using PubMed. Findings revealed an increasing incidence of MS during the last decade. Recent data indicate that latitude does not play a key role in determining the onset of the disease. MS has a significant impact on the quality of life for most patients over many years. The disease is twice as common in women than in men, and is at its peak in the most economically productive years of life. Pregnancy, postpartum status and vaccines may influence the onset and the course of the disease. Only one of the reviewed papers provides a view of progression from onset to death. © 2010 Institute of Psychiatry.
Baloyannis S.J.,Aristotelian University
Future Neurology | Year: 2015
Electron microscopy has enlarged the visual horizons of the morphological alterations in Alzheimer's disease (AD). Study of the mitochondria and Golgi apparatus in early cases of AD revealed the principal role that these important organelles play in the drama of pathogenic dialog of AD, substantially affecting energy production and supply, and protein trafficking in neurons and glia. In addition, study of the morphological alterations of the dendritic arbor, dendritic spines and neuronal synapses, which are associated with mitochondrial damage, may reasonably interpret the clinical phenomena of the irreversible decline of the mental faculties and an individual's personality changes. Electron microscopy also reveals the involvement of microvascular alterations in the etiopathogenic background of AD. © 2015 Future Medicine Ltd.