Effect of cis-(Z)-flupentixol on DPPC membranes in the presence and absence of cholesterol

Cis-(Z)-flupentixol dihydrochloride (FLU), a thioxanthene drug, is used in therapy of schizophrenia as well as in anxiolytic and depressive disorders. Since the action mechanism of FLU is not completely understood, the main objective of present study is to provide a detailed evaluation of flupentixol-phospholipid membrane interactions at molecular level. FLU-dipalmitoylphosphatidylcholine (DPPC) interactions in presence and absence of cholesterol (CHO) were investigated as a function of temperature. The changes in upper part of membrane were more pronounced than those in central part of membrane, as indicated by EPR and FTIR. FLU was proposed to incorporate into phospholipid membranes with its triple ring parallel to head group and its chain toward alkyl chain of phospholipids. According to DSC results, the incorporation of 10 mol% FLU into DPPC caused a shoulder in transition peak, suggesting the occurence of a phase separation, and formation of this new phase is still observable in presence of CHO. It is well known that, structure and dynamics of lipids have significant influence on the function of membrane bound proteins, and consecutively their actions. Based upon these, it was proposed that FLU may modify membrane associated receptors and transport proteins, which would form the basis of its clinical efficiency. (C) 2016 Elsevier Ireland Ltd. All rights reserved

Investigation of neurodegenerative diseases from body fluid samples using Fourier transform infrared spectroscopy

An intriguing feature of infrared (IR) spectroscopy is its capacity to accurately identify and characterize disease morphologies. It enables identification of molecular alterations in wide variety of physiological samples, including but not limited to isolated cellular specimens, body fluid samples and tissue biopsies without the need of using any external agents. Therefore, we aimed to summarize the recent findings on the uses of Fourier Transform IR (FTIR) spectroscopy in assessing the molecular alterations associated with neurodegenerative diseases, a specific group of diseases characterized by progressive and irreversible loss of neuronal cells. In this review, we focus on two specific disease situations, Multiple Sclerosis and Alzheimer's disease, mainly due to the urgent need for identification of a reliable biomarker for their diagnosis. Body fluids, indeed, are very suitable specimens to be used in diagnosis, since they can be easily collected from patients and can accurately reflect biochemical changes. Precise identification of alterations in the molecular profile of body fluid samples from control and affected samples can enable us to identify biomarkers in the diagnosis of aforementioned diseases, and possibly as a crucial clue for developing therapeutical strategies. In this regard, we would like to present current advances in the use of FTIR spectroscopy along with various analysis tools, such as hierarchical cluster analysis (HCA), principal component analysis (PCA). Finally, we present the application of these techniques in Multiple Sclerosis and Alzheimer's disease

Relapsing-Remitting Multiple Sclerosis diagnosis from cerebrospinal fluids via Fourier transform infrared spectroscopy coupled with multivariate analysis

Abstract Multiple sclerosis (MS) is a chronic, progressive, inflammatory and degenerative disease of central nervous system. Here, we aimed to develop a method for differential diagnosis of Relapsing-Remitting MS (RRMS) and clinically isolated syndrome (CIS) patients, as well as to identify CIS patients who will progress to RRMS, from cerebrospinal fluid (CSF) by infrared (IR) spectroscopy and multivariate analysis. Spectral analyses demonstrated significant differences in the molecular contents, especially in the lipids and Z conformation of DNA of CSF from CIS, CIS to RRMS transformed (TCIS) and RRMS groups. These changes enables the discrimination of diseased groups and controls (individuals with no neurological disease) from each other using hierarchical cluster and principal component analysis. Some CIS samples were consistently clustered in RRMS class, which may indicate that these CIS patients potentially will transform to RRMS over time. Z-DNA band at 795 cm−1 that is existent only in diseased groups and significant increase in carbonyl amount, decrease in amideI/amide II and lipid/protein ratios observed only for RRMS groups can be used as diagnostic biomarkers. The results of the present study shed light on the early diagnosis of RRMS by IR spectroscopy complemented with multivariate analysis tools