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Journal of Metabolic Syndrome

ISSN: 2167-0943

Open Access

Articles in press and Articles in process

    Short Article Pages: 1 - 1

    Lipidomics as new way to analyse lipid metabolites

    Tomislav Tosti

    The determination of the lipidome profile is often called lipidomics. The lipidome represents all the small molecules metabolomes whit mass lower than 1500 in system. In recent years, the crucial role of lipidomes in the pathogenesis and therapy of deseases has become increasingly apparent. For example, ischemia-reperfusion (IR) injury can initiate oxidative stress that leads to harmful changes in membrane lipids, with an unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of IR disorders and reveals new targets for drug action. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death The framework of this lecture is analysis of the lipid metabolites and other products that can affect the metabolites of lipids. We analyzed lipid profile of heart, lung, brain kidney liver. The carbohydrate profile was also examined. Based on these results we tried to correlate it with various metabolic processes. In order to obtained even better conclusions the chemometrics was employed. The obtained results showed similarities between hearts and lung, whereas liver and brain exhibits specific behavior. Modern mass spectrometric technologies provide quantitative readouts for a wide variety of lipid specimens. However, many studies do not report absolute lipid concentrations and differ vastly in methodologies, workflows and data presentation. Therefore, we encourage researchers to engage with the Lipidomics Standards Initiative to develop common standards for minimum acceptable data quality and reporting for lipidomics data, to take lipidomics research to the next level Lipidomics has evolved rapidly over the past decade because it offers new opportunities for studying the roles of lipids in cellular biology as well as in health and disease. The lipidomes of eukaryotic cells comprise hundreds of individual lipid species that structurally and chemically regulate cell membrane dynamics, store energy and/or serve as precursors of bioactive metabolites. Membranes of cells and organelles have unique lipid compositions that are intimately linked to their biological functions. The biophysical properties of membranes are also affected by seemingly minor structural differences among individual lipid species, such as the number, position and geometry of double bonds in acyl chains. These characteristics drive membrane budding and fission events and may regulate protein function. Lipid species in membranes act not as single molecules but as a collective, and must be analysed quantitatively and comprehensively to understand their biological function.

    Short Article Pages: 2 - 2

    Targeted LC-MS approach for indirect separation of chiral metabolites

    Radu-Cristian Moldovan

    Since the descovery of D-serine as an endogenous metabolite, chiral metabolomics has become more and more prevalent, exploring the role of chirality in development and progression of different diseases. In biological systems, the most notable class of chiral metabolites is represented by amino acids. It is well known that in mammals the L- enantiomer of amino acids (AA) is naturally occurring. Nevertheless, D-AAs are present in very low concentrations (low nM to low µM range) compared to L-AAs (low µM to mM range), impeding their detection and quantification. Even though many analytical approaches have been developed, most of them are difficult to implement since they require special infrastructure (2D-LC-MS) or expensive chiral selectors. The objective of our study was to develop a fast UHPLC-MS method capable to offer baseline enantiomeric resolution (Rs>2) for all proteinogenic amino acids, using the indirect enantioseparation approach. The starting point were some several observations made in the past [1,2], where a dependance of chiral resolution on mobile phase pH was documented. Therefore, several qualitative variables were identified and included in the study, such as: chiral derivatization reagent (CDA), stationary phase, aqueous phase pH and the nature of organic modifier. Two CDAs were selected: (+)-1-(9-Fluorenyl)ethyl chloroformate ((+)-FLEC) and N-(4-Nitrophenoxycarbonyl)-Lphenylalanine 2-methoxyethyl ester ((S)-NIFE), together with five stationary phases (C18, Polar-C19, PS-C18, Phenyl and F5), two organic modifiers (acetonitrile and methanol) and a pH range between 2 and 8. After a comprehensive screening of these variables, it was observed that (S)-NIFE and acetonitrile have a positive impact on enantioseparation, as compared to (+)-FLEC and methanol, respectively. A further optimization using design of experiments was carried out for finding the best gradient and for fine tuning the pH of the aqueous phase. In optimal conditions, baseline chiral separation of all proteinogenic D- and L-amino acids was achieved in less than 20 minutes.

    Short Article Pages: 3 - 3

    1H-NMR metabolomic study: Effect of very-low-calorie ketogenic diet on psoriasis patients

    Manuela Grimaldi

    Psoriasis is an inflammatory and multifaceted disease of the epidermis based on an immunological mechanism involving Langerhans cells and T lymphocytes that produce proinflammatory cytokines. Genetic factors, environmental factors, and improper nutrition are considered triggers of the disease. Numerous studies have reported that in a high number of patients, psoriasis is associated with obesity. Excess adipose tissue, typical of obesity, causes a systemic inflammatory status coming from the inflammatory active adipose tissue; therefore, weight reduction is a strategy to fight this pro-inflammatory state. We performed a NMR metabolomic study in order to evaluate how a nutritional regimen based on a ketogenic diet, characterized by a reduction in carbohydrates and a relative increase in protein and fat, influences the clinical parameters, metabolic profile, and inflammatory state of psoriasis patients. Thirty (30) psoriasis patients were subjected to a ketogenic nutritional regimen and monitored for 4 weeks by evaluating the clinical data, biochemical and clinical parameters, NMR metabolomic profile, and IL-2, IL-1β, TNF-α, IFN-γ, and IL-4 concentrations before and after the nutritional regimen. Metabolomic profiles of psoriasis patients compared to those of healthy controls before and after a 4 week ketogenic diet provided preliminary indications to identify candidate biomarkers useful in the theranostic control of psoriasis. Results of the metabolic pathway analysis reveal the therapeutic potential of a dietary regimen and provide new insights into the etiopathogenesis of psoriasis. Manuela Grimaldi is a Researcher at the Department of Pharmacy at University of Salerno, involved in the realization of a project entitled "NMR metabolomic characterization of cancerous tissues and biological fluids." In 2007 she graduated in Pharmaceutical Chemistry and Technologies and in the following years she obtained the Specialization in Hospital Pharmacy and the PhD in Pharmaceutical Sciences with a thesis entitled “NMR study of protein-ligand interaction”.

    Short Article Pages: 4 - 4

    Freshwater macrophyte metabolomics: Progress and prospects

    Evgeny Kurashov

    The history of the study of allelopathy in aquatic ecosystems goes back over 100 years. However, the importance of this phenomenon for understanding the structural and functional organization of aquatic ecosystems is beginning to become clear only now. The known information on the low molecular weight metabolome (LMWM) of various macrophytes demonstrates that over 1500 different LMWOCs (low molecular weight organic compounds) can be found in its composition. Moreover, the number of LMWOCs in certain plant species growing in certain habitats can exceed 200 compounds. It is shown that there are patterns of formation and changes in LMWM macrophytes, both depending on the geographical place of plant growth, and the impact of various biotic and abiotic factors. Particular attention is drawn to the issues related to the study of the allelopathy of macrophytes in freshwater ecosystems. For macrophytes of various ecological groups, their inhibiting allelochemicals are described, as well as ecological targets - algae, and cyanobacteria. The direction of studying the potential biological activities of major LMWOCs of aquatic macrophytes using the QSAR method is of great importance. The questions of the chemical protection of aquatic plants against consumers, pests, and pathogens are of theoretical and practical importance. It is shown that it is realistic to create new generation algicides based on natural allelochemicals to prevent and suppress the "bloom" of water bodies. The allelopathy (as a natural phenomenon) can be used for the development of a nature-like convergent technology to control the “bloom” in aquatic ecosystems. Metabolomics is the scientific study of chemical processes involving metabolites, the small molecule substrates, intermediates and products of cell metabolism. The metabolome represents the complete set of metabolites in a biological cell, tissue, organ or organism, which are the end products of cellular processes. Messenger RNA (mRNA), gene expression data and proteomic analyses reveal the set of gene products being produced in the cell, data that represents one aspect of cellular function.

    Short Article Pages: 5 - 5

    Comparative enzyme kinetics analysis of the cDNA-expressed, microsomal and purified mammalian P450 monooxygenases family

    Ilya B. Tsyrlov

    Since the descovery of D-serine as an endogenous metabolite, chiral metabolomics has become more and more prevalent, exploring the role of chirality in development and progression of different diseases. In biological systems, the most notable class of chiral metabolites is represented by amino acids. It is well known that in mammals the L- enantiomer of amino acids (AA) is naturally occurring. Nevertheless, D-AAs are present in very low concentrations (low nM to low µM range) compared to L-AAs (low µM to mM range), impeding their detection and quantification. Even though many analytical approaches have been developed, most of them are difficult to implement since they require special infrastructure (2D-LC-MS) or expensive chiral selectors. The objective of our study was to develop a fast UHPLC-MS method capable to offer baseline enantiomeric resolution (Rs>2) for all proteinogenic amino acids, using the indirect enantioseparation approach. The starting point were some several observations made in the past [1,2], where a dependance of chiral resolution on mobile phase pH was documented. Therefore, several qualitative variables were identified and included in the study, such as: chiral derivatization reagent (CDA), stationary phase, aqueous phase pH and the nature of organic modifier. Two CDAs were selected: (+)-1-(9-Fluorenyl)ethyl chloroformate ((+)-FLEC) and N-(4-Nitrophenoxycarbonyl)-Lphenylalanine 2-methoxyethyl ester ((S)-NIFE), together with five stationary phases (C18, Polar-C19, PS-C18, Phenyl and F5), two organic modifiers (acetonitrile and methanol) and a pH range between 2 and 8. After a comprehensive screening of these variables, it was observed that (S)-NIFE and acetonitrile have a positive impact on enantioseparation, as compared to (+)-FLEC and methanol, respectively. A further optimization using design of experiments was carried out for finding the best gradient and for fine tuning the pH of the aqueous phase. In optimal conditions, baseline chiral separation of all proteinogenic D- and L-amino acids was achieved in less than 20 minutes.

      Research Pages: 1 - 20

      Fibrates and CKD patients: A Controversial issue

      Aber Halim Baky

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      Case Report Pages: 1 - 16

      Prevalence of Metabolic Syndrome in local population of Indore according to IDF criteria

      SADHNA NOTWANI

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      Book Review Pages: 1 - 8

      Metabolic Syndrome

      Puspita Sari

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      Short Article Pages: 1 - 1

      Assessment of quality of life among type 2 diabetes patients and its associated risk factors

      Amena Aidibi

      Diabetes is a growing problem worldwide where its incidence and prevalence are increasing at an alarming rate. Its association with several comorbidities is common, making patients more susceptible to drug related problems (DRP). As a consequence, DRPs may affect patients quality of life (QoL) and may increase their morbidity and mortality risk. The objective of this study was to assess QoL and the impact of DRPs on it. A cross-sectional study was conducted among T2D patients who were attending a tertiary care teaching hospital, Lebanon. Data was collected from medical files and patient interview. The identification DRPs were based on the Pharmaceutical Care Network Europe tool version 8.03. The QoL was assessed using Health Related Quality of Life Brief Clinical Inventory. Data was analyzed using SPSS version 23. The total number of DRP was 313 with a mean of 2.05±1.03 per patient. The most common DRPs encountered were adverse drug event (31.3%), untreated symptoms or indication (10.54%), effect of drug treatment not optimal (7.34%) and high drug dose (7.34%). The average QoL was 40 ± 9.900. Linear regression showed that problems ”effect of drug treatment not optimal, untreated indication, adverse drug event and Patient uses unnecessary drug” were associated with poor QoL score, while “Incomplete drug treatment was associated with better score. Proper therapy management is necessary to prevent progression and occurrence of DRPs, for a better QoL in diabetes patients. Diabetic patients usually have co-morbidities requiring the use of multiple medications, making them more vulnerable in experiencing drug related problems (DRPs). The objective of this study was to asses DRP in type 2 diabetes (T2D) patients and factors associated with its occurrence. A cross-sectional study was conducted among T2D patients who were attending a tertiary care teaching hospital, Lebanon. The identification and assessment of DRPs were based on the Pharmaceutical Care Network Europe tool version 8.03. The total number of DRP was 313 with a mean of 2.05 _ 1.03 per patient. The most common DRPs encountered were adverse drug event (31.3%), untreated symptoms or indication (10.54%), effect of drug treatment not optimal (7.34%) and high drug dose (7.34%). Logistic regression showed that polypharmacy and several comorbidities such as stroke, heart failure, renal and liver impairment were common factors significantly associated with different types of DRPs (p<0.005).

      Short Article Pages: 2 - 2

      Metabolic profiling of hydroponics-growing mint (mentha x pepermint var. Piperita) leaves under supercritical fluid extraction

      Ivonne Buitrago, Juan David Galvis, Laura Ceron-Rincon

      Hydroponics consists of production of plants through the supply of required nutrients for their growth and development in the appropriate proportions and under controlled conditions, allowing the nutrients variation directly related to the production and metabolic composition. Recently metabolomics is used for the analysis of quality and searching of useful compounds in food and pharmaceutical industry. Metabolic profiling (metabolomics/metabonomics) is the measurement in biological systems of the complement of low-molecular-weight metabolites and their intermediates that reflects the dynamic response to genetic modification and physiological, pathophysiological, and/or developmental stimuli. Medicinal Plant are also known as functional foods due to its high content in secondary metabolites with important medicinal properties can be considered in the treatment of diseases. These compounds include the flavonoids and the isotiocyanates, the latter are synthesized as product of glucosinolates hydrolysis. Peppermint is an aromatic plant with high benefit due to its phytochemical content, so studying its metabolic production in hydroponic systems comprises great interest and applicability. The main objective was therefore to analyze the variation of volatile compound profiles (obtained from supercritical fluid extraction) for mint leaves in hydroponics growing. This research was conducted to design and construct six hydroponic system, they were divided into three systems with standard nutrient solution and other three with nutrient solution + foliar salicylic acid (2 mM). As results, particular changes were found in the profiles of mint-derived volatile metabolites. These changes were mediated by the selective occurrence and/or content of some monoterpenes such as L-menthone, pulegone, and terpenes such as menthol. The profiling of volatile metabolites could be an excellent tool to evaluate the mint quality in hydroponics growing. This work was supported by Vicerrectoría de Investigaciones at UMNG Project INV-CIAS-2542.

      Short Article Pages: 3 - 3

      Widely targeted metabolomics profiling of methanolic extracts from roots and leaves of Pteris vittata L

      Kieu Oanh T Nguyen

      Statement of the Problem: Pteris vittata L., a common fern known as ‘Chinese Brake Fern’, is native from China and widespread all over the world including Vietnam. It received much attentions in recent years because it was known to be a hyperaccumulator plant of arsenic used in phytoremediation. It is also widely used in traditional Chinese medicine for diverse therapeutic applications, such as the treatment of influenza, dysentery, rheumatism, injury and scabies. Previous qualitative phytochemical screening studies on P. vittata have showed the presence of flavonoids, tannins, resins, glycosides and triterpenoids groups in the crude extract of this species. However, it still attracts little attention on its chemical constituents or bioactivities recently. Hence, we attempt to obtain complete metabolite profiling of P. vittata to provide more information about its chemical constituents in this experiment. Methodology & Theoretical Orientation: Widely targeted metabolomics which is an innovative high-throughput analysis to extend plant metabolites detection based on the optimal single reaction monitoring conditions in triple quadrupole mass spectrometry of thousands authentic compounds in the library, and thus to relative quantify their levels in samples. This sensitive method was applied for 35 root extracts and 35 aerial part methanolic extracts of P.vittata. Findings: In total, 396 metabolites were identified over the limit of detection including 263 primary metabolites and 133 secondary metabolites. Noticeably, the large amount of flavonoids (74), cinnamic acids and derivatives (13), benzoic acids and derivatives (8), coumarins (5), stilbenoids (2), and other phenols (8) change radically our view of this title plant metabolite profile and potentially contributes to the pharmacological activity of P. vittata extracts. Conclusion & Significance: Metabolite profiles of P. vittata which has been reported for the first time can provide comprehensive information for the quality evaluation and further exploitation potential of the plants under study.

      Short Article Pages: 4 - 4

      Identification of putative biomarker for early detection of meloxicam-induced kidney injury in cats: a metabolomic and lipidomic approach

      Sol M. Rivera-Velez

      Statement of the Problem: The repeated administration of the nonsteroidal anti-inflammatory meloxicam damages kidneys in cats. Serum creatinine and symmetric dimethylarginine are used to detect and monitor changes in kidney function. However, these biomarkers do not detect alterations in kidney function earlier than 10 days after the onset of kidney damage. Early detection of meloxicam-induced kidney damage would provide the best chances of maximizing the clinical use of this drug in cats. Unfortunately, biomarkers for detecting early NSAIDinduced kidney damage in cats are yet to be discovered. The purpose of this study is to identify biomarker candidates for detecting early renal changes within 4 days after starting the repeated administration of meloxicam. Methodology & Theoretical Orientation: Cats (n=12) were treated subcutaneously with either saline solution or a labeled dose of meloxicam every 24 h for up to 4 days to induce acute kidney injury. The plasma and urine metabolome and lipidome were determined before and after the administration of the treatments by LC- and GC-MS/MS. Findings: The repeated administration of meloxicam altered the feline plasma and urine metabolome and lipidome as demonstrated by multivariate analysis. By using random forest and receiving operating characteristic analyses, we identified 24 compounds in plasma and urine that could serve as biomarker candidates for discriminating meloxicam-treated from saline-treated cats. In addition, we identified 23 biomarker candidates using the group of meloxicam-treated cats as its own control. Notably, phenylethylamine, nicotinic acid, and oxalic acid were common biomarker candidates observed between and within groups. Conclusion & Significance: This is the first report on the identification of lipidomic and metabolomic changes in urine and plasma induced by the repeated administration of meloxicam to healthy young-adult cats. Early diagnosis of kidney diseases will facilitate effective inter-ventions that may slow down the progression of kidney disease.

      Short Article Pages: 5 - 5

      Diabetes Educator course with a Specialization in Indigenous Health

      Amanda Macdonald

      Diabetes Mellitus is a global epidemic, with 500 million people suffering globally in 2013. Patients cannot successfully manage their diabetic symptoms due to the lack of quality improvement (QI) of diabetic selfmanagement education (DSME). In 2013, this number was 3 to 5 times higher in First Nations populations.The objective of this research is to facilitate better QI and DSME in Indigenous populations across the globe by creating a free, accredited course. This course will educate sustainable health promotion techniques needed for monitoring sugars, mental illness, treating common complications, medication management, and physical and nutritional therapy, to only name a few. Research on the succession will be analysed in a Public Health practice-based research network (PBRNs) method with surveys, interviews, and statistical analysis on short-/long-term effectiveness from baseline tests. These will include: heart rate, blood pressure, mental health, medication, blood sugar levels >3 months, hyper-/hypo-glycaemia, blood circulation, ankle brachial pressure test scores, kidney function, and macrovascular, retinopathy, dermatology and nerve damage complications. These tests will be completed in a small group of remote Indigenous communities in Quebec, Canada. It is hypothesized that this will improve public health efforts of patient selfmanagement of diabetes and its associated symptoms. With this free, accredited, accessible online course to prepare health practitioners in DSME, better glycaemic control, less hospital visits, decreased retinopathy, nephropathy, and neuropathy is expected. Diabetes is a growing problem worldwide where its incidence and prevalence are increasing at an alarming rate. Its association with several comorbidities is common, making patients more susceptible to drug related problems (DRP). As a consequence, DRPs may affect patients quality of life (QoL) and may increase their morbidity and mortality risk. The objective of this study was to assess QoL and the impact of DRPs on it. A cross-sectional study was conducted among T2D patients who were attending a tertiary care teaching hospital, Lebanon. Data was collected from medical files and patient interview. The identification DRPs were based on the Pharmaceutical Care Network Europe tool version 8.03. The QoL was assessed using Health Related Quality of Life Brief Clinical Inventory. Data was analyzed using SPSS version 23.

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