26 results on '"García-Álvarez I"'
Search Results
2. La consulta no presencial como herramienta de mejora de la consulta a demanda en atención primaria
- Author
-
de la Fuente Ballesteros, S.L., García Granja, N., Hernández Carrasco, M., Hidalgo Benito, A., García Álvarez, I., and García Ramón, E.
- Published
- 2018
- Full Text
- View/download PDF
3. A comprehensive profiling of sulfatides in myelin from mouse brain using liquid chromatography coupled to high-resolution accurate tandem mass spectrometry
- Author
-
Pintado-Sierra, M., García-Álvarez, I., Bribián, A., Medina-Rodríguez, E.M., Lebrón-Aguilar, R., Garrido, L., de Castro, F., Fernández-Mayoralas, A., and Quintanilla-López, J.E.
- Published
- 2017
- Full Text
- View/download PDF
4. A study on partially biodegradable microparticles as carriers of active glycolipids
- Author
-
López-Donaire, M.L., Fernández-Gutiérrez, M., Parra-Cáceres, J., Vázquez-Lasa, B., García-Álvarez, I., Fernández-Mayoralas, A., and Román, J. San
- Published
- 2010
- Full Text
- View/download PDF
5. Polymeric drugs based on bioactive glycosides for the treatment of brain tumours
- Author
-
López Donaire, M.L., Parra-Cáceres, J., Vázquez-Lasa, B., García-Álvarez, I., Fernández-Mayoralas, A., López-Bravo, A., and San Román, J.
- Published
- 2009
- Full Text
- View/download PDF
6. IG20, A NEW GLYCOLIPID, INCREASES THE MEMBRANE EXCITABILITY AND EXOCYTOSIS IN CHROMAFFIN CELLS: 56
- Author
-
Crespo - Castrillo, A., Punzón - Fernández, E., de Pascual, R., Maroto, M., Ruiz-Pascual, L., Calvo- Gallardo, E., Fernández-Mayoralas, A., García-Álvarez, I., and García, A. G.
- Published
- 2014
7. Immunological Status of Elderly Patients Eligible for Arthroplasty after a Femoral Neck Fracture: Relationship between the Patients’ Status, their Age and Postoperative Morbimortality
- Author
-
García-Álvarez, F., Al-Ghanem, R., García-Álvarez, I., Larrad, L., González-Murga, P., López-Baisson, A., Navarro-Zorraquino, M., de Miguel, R., and Lozano-Mantecón, R.
- Published
- 2007
- Full Text
- View/download PDF
8. Estado inmunológico de ancianos candidatos a artroplastia tras fractura subcapital de cadera: estudio de su relación con la edad y con la morbimortalidad postoperatoria
- Author
-
García-Álvarez, F., al-Ghanem, R., García-Álvarez, I., Larrad, L., González-Murga, P., López-Baisson, A., Navarro-Zorraquino, M., de Miguel, R., and Lozano-Mantecón, R.
- Published
- 2007
- Full Text
- View/download PDF
9. Age-linked heterogeneity among oligodendrocyte precursor cells in the cerebral cortex of mice and human
- Author
-
Bribián, A, primary, Medina-Rodríguez, EM, additional, Josa-Prado, F, additional, García-Álvarez, I, additional, Machín-Díaz, I, additional, Murcia-Belmonte, V, additional, Vega-Zelaya, L, additional, Pastor, J, additional, Garrido, L, additional, and de Castro, F, additional
- Published
- 2019
- Full Text
- View/download PDF
10. Glycosides-bearing electrospun poly(hydroxybutyrate-co-hydroxyhexanoate) substrates for the repair of injured spinal cord,Sustratos electrohilados de poli(hidroxibutirato-co-hidroxihexanoato) con glicósidos para reparación de la lesión medular
- Author
-
García-Álvarez, I., Doncel-Pérez, E., García-Junceda, E., Alfonso Fernández-Mayoralas, and Garrido, L.
11. Evaluation of Anti-Neuroinflammatory Activity of Isatin Derivatives in Activated Microglia.
- Author
-
Cenalmor A, Pascual E, Gil-Manso S, Correa-Rocha R, Suárez JR, and García-Álvarez I
- Subjects
- Humans, Anti-Inflammatory Agents pharmacology, Microglia metabolism, Neuroinflammatory Diseases, NF-kappa B metabolism, Lipopolysaccharides pharmacology, Nitric Oxide metabolism, Tumor Necrosis Factor-alpha metabolism, Nitric Oxide Synthase Type II metabolism, Isatin pharmacology, Neuroprotective Agents pharmacology
- Abstract
Neuroinflammation plays a crucial role in the progression of Alzheimer's disease and other neurodegenerative disorders. Overactivated microglia cause neurotoxicity and prolong the inflammatory response in many neuropathologies. In this study, we have synthesised a series of isatin derivatives to evaluate their anti-neuroinflammatory potential using lipopolysaccharide activated microglia as a cell model. We explored four different substitutions of the isatin moiety by testing their anti-neuroinflammatory activity on BV2 microglia cells. Based on the low cytotoxicity and the activity in reducing the release of nitric oxide, pro-inflammatory interleukin 6 and tumour necrosis factor α by microglial cells, the N
1 -alkylated compound 10 and the chlorinated 20 showed the best results at 25 µM. Taken together, the data suggest that 10 and 20 are promising lead compounds for developing new neuroprotective agents., Competing Interests: The authors declare no conflict of interest.- Published
- 2023
- Full Text
- View/download PDF
12. Functional Heterogeneity of Mouse and Human Brain OPCs: Relevance for Preclinical Studies in Multiple Sclerosis.
- Author
-
Bribián A, Medina-Rodríguez EM, Josa-Prado F, García-Álvarez I, Machín-Díaz I, Esteban PF, Murcia-Belmonte V, Vega-Zelaya L, Pastor J, Garrido L, and de Castro F
- Abstract
Besides giving rise to oligodendrocytes (the only myelin-forming cell in the Central Nervous System (CNS) in physiological conditions), Oligodendrocyte Precursor Cells (OPCs) are responsible for spontaneous remyelination after a demyelinating lesion. They are present along the mouse and human CNS, both during development and in adulthood, yet how OPC physiological behavior is modified throughout life is not fully understood. The activity of adult human OPCs is still particularly unexplored. Significantly, most of the molecules involved in OPC-mediated remyelination are also involved in their development, a phenomenon that may be clinically relevant. In the present article, we have compared the intrinsic properties of OPCs isolated from the cerebral cortex of neonatal, postnatal and adult mice, as well as those recovered from neurosurgical adult human cerebral cortex tissue. By analyzing intact OPCs for the first time with 1H High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (1H HR-MAS NMR) spectroscopy, we show that these cells behave distinctly and that they have different metabolic patterns in function for their stage of maturity. Moreover, their response to Fibroblast Growth Gactor-2 (FGF-2) and anosmin-1 (two molecules that have known effects on OPC biology during development and that are overexpressed in individuals with Multiple Sclerosis (MS)) differs in relation to their developmental stage and in the function of the species. Our data reveal that the behavior of adult human and mouse OPCs differs in a very dynamic way that should be very relevant when testing drugs and for the proper design of effective pharmacological and/or cell therapies for MS.
- Published
- 2020
- Full Text
- View/download PDF
13. Neurotransmitter-Responsive Nanosensors for T 2 -Weighted Magnetic Resonance Imaging.
- Author
-
Hsieh V, Okada S, Wei H, García-Álvarez I, Barandov A, Alvarado SR, Ohlendorf R, Fan J, Ortega A, and Jasanoff A
- Subjects
- Animals, Binding, Competitive, Brain diagnostic imaging, Brain metabolism, Contrast Media administration & dosage, Dopamine analysis, Ligands, Magnetite Nanoparticles administration & dosage, Protein Binding, Rats, Biosensing Techniques methods, Contrast Media chemistry, Magnetic Resonance Imaging methods, Magnetite Nanoparticles chemistry, Neurotransmitter Agents analysis
- Abstract
Neurotransmitter-sensitive contrast agents for magnetic resonance imaging (MRI) have recently been used for mapping signaling dynamics in live animal brains, but paramagnetic sensors for T
1 -weighted MRI are usually effective only at micromolar concentrations that themselves perturb neurochemistry. Here we present an alternative molecular architecture for detecting neurotransmitters, using superparamagnetic iron oxide nanoparticles conjugated to tethered neurotransmitter analogs and engineered neurotransmitter binding proteins. Interactions between the nanoparticle conjugates result in clustering that is reversibly disrupted in the presence of neurotransmitter analytes, thus altering T2 -weighted MRI signals. We demonstrate this principle using tethered dopamine and serotonin analogs, together with proteins selected for their ability to competitively bind either the analogs or the neurotransmitters themselves. Corresponding sensors for dopamine and serotonin exhibit target-selective relaxivity changes of up to 20%, while also operating below endogenous neurotransmitter concentrations. Semisynthetic magnetic particle sensors thus represent a promising path for minimally perturbative studies of neurochemical analytes.- Published
- 2019
- Full Text
- View/download PDF
14. [Tele-medicine consultation as a tool to improve the demand for consultation in Primary Care].
- Author
-
de la Fuente Ballesteros SL, García Granja N, Hernández Carrasco M, Hidalgo Benito A, García Álvarez I, and García Ramón E
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Caregivers statistics & numerical data, Electronic Mail, Female, Humans, Male, Middle Aged, Retrospective Studies, Telephone, Time Factors, Young Adult, Health Services Accessibility, Primary Health Care organization & administration, Referral and Consultation statistics & numerical data, Remote Consultation statistics & numerical data
- Abstract
Objective: Currently, there is a strong healthcare pressure on resources in Primary Care clinics. This significantly compromises the accessibility and the time dedicated to the patient. This paper analyses the implementation of a tele-medicine service using telephone and e-mail consultations., Materials and Methods: The telephone and e-mail consultations carried out during one year were reviewed retrospectively. The patient profile, the type of consultation carried out, the need for a face-to-face visit, and the receipt of attached documentation were analysed., Results: A total of 884 distance consultations were received in a 12month period. The distance consultation accounted for 13.56% of consultations on demand. The mean age of the patient was 54 (SD: 17) years old. The large majority (87.7%) of the consultations were made by the patients and the rest by relatives or caregivers. The time spent per patient in the face-to-face consultation was 10.24minutes and the waiting list was less than 48hours on 97% of the days of the year. The patient had to go in person on 24 (2.71%) occasions., Conclusions: Distance consultation is a useful resource for improving accessibility, as well as leading to more physical consultation time. It has also demonstrated that it is capable of solving problems of different kinds and in different age groups., (Copyright © 2018 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
15. Micellar Iron Oxide Nanoparticles Coated with Anti-Tumor Glycosides.
- Author
-
Groult H, García-Álvarez I, Romero-Ramírez L, Nieto-Sampedro M, Herranz F, Fernández-Mayoralas A, and Ruiz-Cabello J
- Abstract
The synthesis procedure of nanoparticles based on thermal degradation produces organic solvent dispersible iron oxide nanoparticles (OA-IONP) with oleic acid coating and unique physicochemical properties of the core. Some glycosides with hydrophilic sugar moieties bound to oleyl hydrophobic chains have antimitotic activity on cancer cells but reduced in vivo applications because of the intrinsic low solubility in physiological media, and are prone to enzymatic hydrolysis. In this manuscript, we have synthetized and characterized OA-IONP-based micelles encapsulated within amphiphilic bioactive glycosides. The glycoside-coated IONP micelles were tested as Magnetic Resonance Imaging (MRI) contrast agents as well as antimitotics on rat glioma (C6) and human lung carcinoma (A549) cell lines. Micelle antimitotic activity was compared with the activity of the corresponding free glycosides. In general, all OA-IONP-based micellar formulations of these glycosides maintained their anti-tumor effects, and, in one case, showed an unusual therapeutic improvement. Finally, the micelles presented optimal relaxometric properties for their use as T2-weighed MRI contrast agents. Our results suggest that these bioactive hydrophilic nano-formulations are theranostic agents with synergistic properties obtained from two entities, which separately are not ready for in vivo applications, and strengthen the possibility of using biomolecules as both a coating for OA-IONP micellar stabilization and as drugs for therapy.
- Published
- 2018
- Full Text
- View/download PDF
16. Novel sulfoglycolipid IG20 causes neuroprotection by activating the phase II antioxidant response in rat hippocampal slices.
- Author
-
Punzón E, García-Alvarado F, Maroto M, Fernández-Mendívil C, Michalska P, García-Álvarez I, Arranz-Tagarro JA, Buendia I, López MG, León R, Gandía L, Fernández-Mayoralas A, and García AG
- Subjects
- Adenosine Triphosphate metabolism, Animals, Antioxidants chemistry, Cell Hypoxia drug effects, Cell Survival drug effects, Cell Survival physiology, Cells, Cultured, Glucose deficiency, Glutamic Acid toxicity, Glutathione metabolism, Glycolipids chemistry, Hippocampus metabolism, Male, Membrane Potentials drug effects, Membrane Potentials physiology, Molecular Structure, Neuroprotective Agents chemistry, Nitric Oxide Synthase Type II metabolism, Rats, Sprague-Dawley, Reactive Oxygen Species metabolism, Tissue Culture Techniques, Veratridine toxicity, Antioxidants pharmacology, Glycolipids pharmacology, Hippocampus drug effects, Neuroprotective Agents pharmacology
- Abstract
Compound IG20 is a newly synthesised sulphated glycolipid that promotes neuritic outgrowth and myelinisation, at the time it causes the inhibition of glial proliferation and facilitates exocytosis in chromaffin cells. Here we have shown that IG20 at 0.3-10 μM afforded neuroprotection in rat hippocampal slices stressed with veratridine, glutamate or with oxygen plus glucose deprivation followed by reoxygenation (OGD/reox). Excess production of reactive oxygen species (ROS) elicited by glutamate or ODG/reox was prevented by IG20 that also restored the depressed tissue levels of GSH and ATP in hippocampal slices subjected to OGD/reox. Furthermore, the augmented iNOS expression produced upon OGD/reox exposure was also counteracted by IG20. Additionally, the IG20 elicited neuroprotection was prevented by the presence of inhibitors of the signalling pathways Jak2/STAT3, MEK/ERK1/2, and PI3K/Akt, consistent with the ability of the compound to increase the phosphorylation of Jak2, ERK1/2, and Akt. Thus, the activation of phase II response and the Nrf2/ARE pathway could explain the antioxidant and anti-inflammatory effects and the ensuing neuroprotective actions of IG20., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
17. Novel synthetic sulfoglycolipid IG20 facilitates exocytosis in chromaffin cells through the regulation of sodium channels.
- Author
-
Crespo-Castrillo A, Punzón E, de Pascual R, Maroto M, Padín JF, García-Álvarez I, Nanclares C, Ruiz-Pascual L, Gandía L, Fernández-Mayoralas A, and García AG
- Subjects
- Animals, Azoles metabolism, Azoles pharmacology, Cadmium pharmacology, Calcium metabolism, Catecholamines metabolism, Cattle, Cells, Cultured, Chromaffin Cells physiology, Cytosol drug effects, Cytosol metabolism, Enzyme Inhibitors pharmacology, Fura-2 analogs & derivatives, Fura-2 metabolism, Glycolipids metabolism, Membrane Transport Modulators pharmacology, Nifedipine pharmacology, Nitrobenzenes metabolism, Nitrobenzenes pharmacology, Potassium metabolism, Potassium pharmacology, Sodium metabolism, Tetrodotoxin pharmacology, Thapsigargin pharmacology, Chromaffin Cells drug effects, Exocytosis drug effects, Glycolipids pharmacology, Sodium Channels physiology
- Abstract
In search of druggable synthetic lipids that function as potential modulators of synaptic transmission and plasticity, we synthesized sulfoglycolipid IG20, which stimulates neuritic outgrowth. Here, we have explored its effects on ion channels and exocytosis in bovine chromaffin cells. IG20 augmented the rate of basal catecholamine release. Such effect did not depend on Ca(2+) mobilization from intracellular stores; rather, IG20-elicited secretion entirely dependent on Ca(2+) entry through L-subtype voltage-activated Ca(2+) channels. Those channels were recruited by cell depolarization mediated by IG20 likely through its ability to enhance the recruitment of Na(+) channels at more hyperpolarizing potentials. Confocal imaging with fluorescent derivative IG20-NBD revealed its rapid incorporation and confinement into the plasmalemma, supporting the idea that IG20 effects are exerted through a plasmalemmal-delimited mechanism. Thus, synthetic IG20 seems to mimic several physiological effects of endogenous lipids such as regulation of ion channels, Ca(2+) signaling, and exocytosis. Therefore, sulfoglycolipid IG20 may become a pharmacological tool for investigating the role of the lipid environment on neuronal excitability, ion channels, neurotransmitter release, synaptic efficacy, and neuronal plasticity. It may also inspire the synthesis of druggable sulfoglycolipids aimed at increasing synaptic plasticity and efficacy in neurodegenerative diseases and traumatic brain-spinal cord injury. The novel synthetic sulfoglycolipid IG20 mimics several physiological effects of endogenous lipids such as regulation of ion channels, Ca(2+) signaling, and exocytosis. This profile may eventually drive enhanced synaptic plasticity and efficacy., (© 2015 International Society for Neurochemistry.)
- Published
- 2015
- Full Text
- View/download PDF
18. New oleyl glycoside as anti-cancer agent that targets on neutral sphingomyelinase.
- Author
-
Romero-Ramírez L, García-Álvarez I, Casas J, Barreda-Manso MA, Yanguas-Casás N, Nieto-Sampedro M, and Fernández-Mayoralas A
- Subjects
- Animals, Cell Line, Tumor, Ceramides metabolism, Dose-Response Relationship, Drug, Drug Delivery Systems, Glycosides chemistry, Rats, Antineoplastic Agents administration & dosage, Antineoplastic Agents metabolism, Glycosides administration & dosage, Glycosides metabolism, Sphingomyelin Phosphodiesterase metabolism
- Abstract
We designed and synthesized two anomeric oleyl glucosaminides as anti-cancer agents where the presence of a trifluoroacetyl group close to the anomeric center makes them resistant to hydrolysis by hexosaminidases. The oleyl glycosides share key structural features with synthetic and natural oleyl derivatives that have been reported to exhibit anti-cancer properties. While both glycosides showed antiproliferative activity on cancer cell lines, only the α-anomer caused endoplasmic reticulum (ER) stress and cell death on C6 glioma cells. Analysis of sphingolipids and glycosphingolipds in cells treated with the glycosides showed that the α-anomer caused a drastic accumulation of ceramide and glucosylceramide and reduction of lactosylceramide and GM3 ganglioside at concentrations above a threshold of 20 μM. In order to understand how ceramide levels increase in response to α-glycoside treatment, further investigations were done using specific inhibitors of sphingolipid metabolic pathways. The pretreatment with 3-O-methylsphingomyelin (a neutral sphingomyelinase inhibitor) restored sphingomyelin levels together with the lactosylceramide and GM3 ganglioside levels and prevented the ER stress and cell death caused by the α-glycoside. The results indicated that the activation of neutral sphingomyelinase is the main cause of the alterations in sphingolipids that eventually lead to cell death. The new oleyl glycoside targets a key enzyme in sphingolipid metabolism with potential applications in cancer therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
19. Inhibition of glial proliferation, promotion of axonal growth and myelin production by synthetic glycolipid: A new approach for spinal cord injury treatment.
- Author
-
García-Álvarez I, Fernández-Mayoralas A, Moreno-Lillo S, Sánchez-Sierra M, Nieto-Sampedro M, and Doncel-Pérez E
- Subjects
- Animals, Astrocytes drug effects, Astrocytes pathology, Astrocytes physiology, Axons drug effects, Axons pathology, Axons physiology, Cell Proliferation drug effects, Cell Proliferation physiology, Cells, Cultured, Cicatrix drug therapy, Cicatrix pathology, Cicatrix physiopathology, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Female, Ganglia, Spinal drug effects, Ganglia, Spinal pathology, Ganglia, Spinal physiopathology, Glycolipids chemical synthesis, Glycolipids chemistry, Microglia drug effects, Microglia pathology, Microglia physiology, Molecular Structure, Motor Activity drug effects, Motor Activity physiology, Myelin Sheath drug effects, Myelin Sheath pathology, Myelin Sheath physiology, Neuroprotective Agents chemical synthesis, Neuroprotective Agents chemistry, Rats, Wistar, Recovery of Function drug effects, Recovery of Function physiology, Spinal Cord Injuries pathology, Spinal Cord Injuries physiopathology, Glycolipids pharmacology, Neuroprotective Agents pharmacology, Spinal Cord Injuries drug therapy
- Abstract
Purpose: After spinal cord injury (SCI) a glial scar is generated in the area affected that forms a barrier for axon growth and myelination, preventing functional recovery. Recently, we have described a synthetic glycolipid (IG20) that inhibited proliferation of human glioma cells. We show now that IG20 inhibited the proliferation of astrocytes and microglial cells, the principal cellular components of the glial scar, and promoting axonal outgrowth and myelin production in vitro., Methods: Glial cells were inhibited with IG20 (IC50≈10 μM) and studied by RT-PCR, Western Blotting, immunoprecipitation and fluorescence microscopy. Axonal outgrowth in dorsal root ganglia (DRG) and myelin production by oligodendrocytes were analyzed by immunocytochemistry. Adult rats were assayed in spinal cord contusion model and the recovery of treated animals (n = 6) and controls (n = 6) was followed., Results: The IG20 was localized in the cytosol of glial cells, forming a complex with RhoGDIα, a regulator of RhoGTPases. Treatment of astroglial cultures with IG20 increase the expression of BDNF receptor genes (TrkBT1, TrkB Full). IG20 reduced the astroglial marker GFAP, while increasing production of myelin basic protein in oligodendrocytes and promoted axonal outgrowth from DRG neurons. Local injection of IG20, near a spinal cord contusion, promoted the recovery of lesioned animals analyzed by BBB test (P < 0.05)., Conclusions: We propose that inhibition of astrocytes and microglia by IG20 could be diminished the glial scar formation, inducing the re-growth and myelination of axons, these elements constitute a new approach for SCI therapy.
- Published
- 2015
- Full Text
- View/download PDF
20. Mass Spectrometry in Pharmacokinetic Studies of a Synthetic Compound for Spinal Cord Injury Treatment.
- Author
-
Sánchez-Sierra M, García-Álvarez I, Fernández-Mayoralas A, Moreno-Lillo S, Barroso García G, Moral Dardé V, and Doncel-Pérez E
- Subjects
- Animals, Central Nervous System drug effects, Central Nervous System metabolism, Central Nervous System physiopathology, Disease Models, Animal, Glycolipids chemical synthesis, Glycolipids pharmacokinetics, Humans, Male, Rats, Rats, Sprague-Dawley, Spinal Cord drug effects, Spinal Cord physiopathology, Spinal Cord Injuries pathology, Glycolipids administration & dosage, Mass Spectrometry, Spinal Cord Injuries blood, Spinal Cord Injuries drug therapy
- Abstract
The studies of drugs that could constitute a palliative to spinal cord injury (SCI) are a continuous and increasing demand in biomedicine field from developed societies. Recently we described the chemical synthesis and antiglioma activity of synthetic glycosides. A synthetic sulfated glycolipid (here IG20) has shown chemical stability, solubility in polar solvents, and high inhibitory capacity over glioma growth. We have used mass spectrometry (MS) to monitor IG20 (m/z = 550.3) in cells and tissues of the central nervous system (CNS) that are involved in SCI recovery. IG20 was detected by MS in serum and homogenates from CNS tissue of rats, though in the latter a previous deproteinization step was required. The pharmacokinetic parameters of serum clearance at 24 h and half-life at 4 h were determined for synthetic glycoside in the adult rat using MS. A local administration of the drug near of spinal lesion site is proposed.
- Published
- 2015
- Full Text
- View/download PDF
21. The effect of antitumor glycosides on glioma cells and tissues as studied by proton HR-MAS NMR spectroscopy.
- Author
-
García-Álvarez I, Garrido L, Romero-Ramírez L, Nieto-Sampedro M, Fernández-Mayoralas A, and Campos-Olivas R
- Subjects
- Analysis of Variance, Animals, Cell Death drug effects, Cell Line, Tumor, Choline metabolism, Glioma metabolism, Glycosides chemistry, Mice, Mice, Nude, Molecular Structure, Phospholipids metabolism, Rats, Taurine metabolism, Antineoplastic Agents pharmacology, Cell Proliferation drug effects, Glioma drug therapy, Glycosides pharmacology, Magnetic Resonance Spectroscopy methods
- Abstract
The effect of the treatment with glycolipid derivatives on the metabolic profile of intact glioma cells and tumor tissues, investigated using proton high resolution magic angle spinning ((1)H HR-MAS) nuclear magnetic resonance (NMR) spectroscopy, is reported here. Two compounds were used, a glycoside and its thioglycoside analogue, both showing anti-proliferative activity on glioma C6 cell cultures; however, only the thioglycoside exhibited antitumor activity in vivo. At the drug concentrations showing anti-proliferative activity in cell culture (20 and 40 µM), significant increases in choline containing metabolites were observed in the (1)H NMR spectra of the same intact cells. In vivo experiments in nude mice bearing tumors derived from implanted C6 glioma cells, showed that reduction of tumor volume was associated with significant changes in the metabolic profile of the same intact tumor tissues; and were similar to those observed in cell culture. Specifically, the activity of the compounds is mainly associated with an increase in choline and phosphocholine, in both the cell cultures and tumoral tissues. Taurine, a metabolite that has been considered a biomarker of apoptosis, correlated with the reduction of tumor volume. Thus, the results indicate that the mode of action of the glycoside involves, at least in part, alteration of phospholipid metabolism, resulting in cell death.
- Published
- 2013
- Full Text
- View/download PDF
22. Synthetic glycolipids for glioma growth inhibition developed from neurostatin and NF115 compound.
- Author
-
Doncel-Pérez E, García-Álvarez I, Fernández-Mayoralas A, and Nieto-Sampedro M
- Subjects
- Acetylglucosamine chemistry, Acetylglucosamine pharmacology, Cell Line, Tumor, Cell Proliferation drug effects, Gene Expression Regulation, Glycolipids chemistry, Glycolipids pharmacology, Glycosphingolipids pharmacology, Humans, Microarray Analysis, Propylene Glycols pharmacology, rho Guanine Nucleotide Dissociation Inhibitor alpha genetics, rho Guanine Nucleotide Dissociation Inhibitor alpha metabolism, Acetylglucosamine analogs & derivatives, Glioma drug therapy, Glycolipids chemical synthesis, Glycosphingolipids chemistry, Propylene Glycols chemistry
- Abstract
Neurostatin, a natural glycosphingolipid, and NF115, a synthetic glycolipid, are inhibitors of glioma growth. While neurostatin shows high inhibitory activity on gliomas its abundance is low in mammalian brain. On the contrary NF115 exhibits less inhibitory activity on gliomas, but could be prepared by chemical synthesis. In this study we describe synthetic compounds, structurally related to NF115, capable of inhibiting glioma growth at low micromolar range. We used DNA microarray technology to compare the genes inhibited in U373-MG human glioma cells after treatment with the natural or synthetic inhibitor. New synthetic compounds were developed to interact with the product of Rho GDP dissociation inhibitor alpha gene, which was repressed in both treatments. Compounds that were inhibitors of glioma cell growth in assays for [3H]-thymidine incorporation were then injected in C6 tumor bearing rats and the tumor size in each animal group were measured. The GC-17, GC-4 and IG-5 are new compounds derived from NF115 and showed high antiproliferative activity on tumor cell lines. The GC-17 compound inhibited U373-MG glioblastoma cells (3.2 μM), the effects was fifty times more potent than NF115, and caused a significant reduction of tumor volume (P<0.05) when tested in Wistar rats allotransplanted with C6 glioma cells., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
23. Specific synthesis of neurostatin and gangliosides O-acetylated in the outer sialic acids using a sialate transferase.
- Author
-
Romero-Ramírez L, García-Álvarez I, Campos-Olivas R, Gilbert M, Goneau MF, Fernández-Mayoralas A, and Nieto-Sampedro M
- Subjects
- Acetylation, Acetyltransferases isolation & purification, Campylobacter jejuni enzymology, Carbohydrate Sequence, Chromatography, High Pressure Liquid, Chromatography, Thin Layer, Gangliosides chemistry, Glycosphingolipids chemistry, Magnetic Resonance Spectroscopy, Molecular Sequence Data, Recombinant Proteins chemistry, Recombinant Proteins isolation & purification, Spectrometry, Mass, Electrospray Ionization, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Acetyltransferases chemistry, Gangliosides chemical synthesis, Glycosphingolipids chemical synthesis, Sialic Acids chemistry
- Abstract
Gangliosides are sialic acid containing glycosphingolipids, commonly found on the outer leaflet of the plasma membrane. O-acetylation of sialic acid hydroxyl groups is one of the most common modifications in gangliosides. Studies on the biological activity of O-acetylated gangliosides have been limited by their scarcity in nature. This comparatively small change in ganglioside structure causes major changes in their physiological properties. When the ganglioside GD1b was O-acetylated in the outer sialic acid, it became the potent inhibitor of astroblast and astrocytoma proliferation called Neurostatin. Although various chemical and enzymatic methods to O-acetylate commercial gangliosides have been described, O-acetylation was nonspecific and produced many side-products that reduced the yield. An enzyme with O-acetyltransferase activity (SOAT) has been previously cloned from the bacteria Campylobacter jejuni. This enzyme catalyzed the acetylation of oligosaccharide-bound sialic acid, with high specificity for terminal alpha-2,8-linked residues. Using this enzyme and commercial gangliosides as starting material, we have specifically O-acetylated the gangliosides' outer sialic acids, to produce the corresponding gangliosides specifically O-acetylated in the sialic acid bound in alpha-2,3 and alpha-2,8 residues. We demonstrate here that O-acetylation occurred specifically in the C-9 position of the sialic acid. In summary, we present a new method of specific O-acetylation of ganglioside sialic acids that permits the large scale preparation of these modified glycosphingolipids, facilitating both, the study of their mechanism of antitumoral action and their use as therapeutic drugs for treating glioblastoma multiform (GBM) patients.
- Published
- 2012
- Full Text
- View/download PDF
24. Synthesis of antimitotic thioglycosides: in vitro and in vivo evaluation of their anticancer activity.
- Author
-
García-Álvarez I, Groult H, Casas J, Barreda-Manso MA, Yanguas-Casás N, Nieto-Sampedro M, Romero-Ramírez L, and Fernández-Mayoralas A
- Subjects
- Animals, Antimitotic Agents chemistry, Antimitotic Agents pharmacology, Cell Line, Tumor, Drug Screening Assays, Antitumor, Glycolipids chemistry, Glycolipids pharmacology, Humans, Hydrolysis, Mice, Mice, Nude, Neoplasm Transplantation, Rats, Structure-Activity Relationship, Thioglucosides chemistry, Thioglucosides pharmacology, Thioglycosides chemistry, Thioglycosides pharmacology, Transplantation, Heterologous, Tumor Burden drug effects, beta-N-Acetylhexosaminidases chemistry, Antimitotic Agents chemical synthesis, Glycolipids chemical synthesis, Thioglucosides chemical synthesis, Thioglycosides chemical synthesis
- Abstract
The synthesis and biological activity of oleylN-acetyl-α- and β-d-glucosaminides (1 and 2, respectively) and their thioglycosyl analogues (3 and 4, respectively) are reported. The compounds exhibited antimitotic activity on rat glioma (C6) and human lung carcinoma (A549) cell cultures in the micromolar range. Analysis of cell extracts using ultra performance liquid chromatography-mass spectrometry showed that the synthetic glycosides produce alterations in glycosphingolipid metabolism, with variable effect on the level of glucosylceramide depending on the configuration of the antimitotic used. In vivo experiments in nude mice bearing an implanted C6 glioma showed that the α-thioglycoside 3 reduced tumor volume, while the O-glycosyl derivative was inactive, highlighting the importance of using enzyme resistant glycosides.
- Published
- 2011
- Full Text
- View/download PDF
25. Effect of drugs in cells and tissues by NMR spectroscopy.
- Author
-
García-Álvarez I, Fernández-Mayoralas A, and Garrido L
- Subjects
- Animals, Chemistry, Pharmaceutical, Drug Delivery Systems, Humans, Magnetic Resonance Spectroscopy instrumentation, Sensitivity and Specificity, Magnetic Resonance Spectroscopy methods
- Abstract
In this article, the application of high resolution NMR spectroscopy to study the effect of therapeutic compounds on cells, tissues and organisms is reviewed. To illustrate how these NMR methods can provide useful information for a better understanding about the mechanism of action of drugs and their interactions with metabolic pathways, the emphasis is placed on most recent work about drug therapeutic intervention in biological models of diseases and in humans. Specifically, the application of NMR spectroscopy to investigate the effect of drugs on the treatment of neurological disorders, cancer, infectious diseases and diabetes is illustrated. In addition, NMR studies of drug-induced toxicity and multinuclear NMR for monitoring drug delivery and catabolism are described. Current progress in NMR instrumentation and methods will continue to improve the sensitivity and maintain this very versatile technique as powerful tool for research in the field of medicinal chemistry.
- Published
- 2011
- Full Text
- View/download PDF
26. Lipid and ganglioside alterations in tumor cells treated with antimitotic oleyl glycoside.
- Author
-
García-Álvarez I, Egido-Gabás M, Romero-Ramírez L, Doncel-Pérez E, Nieto-Sampedro M, Casas J, and Fernández-Mayoralas A
- Subjects
- Animals, Antigens, CD metabolism, Antimitotic Agents chemistry, Cell Line, Tumor, Chromatography, High Pressure Liquid, Enzyme Activation drug effects, Glucosyltransferases metabolism, Glycosides chemistry, Humans, Lactosylceramides metabolism, Magnetic Resonance Spectroscopy, Mass Spectrometry, Models, Biological, Rats, Transferases (Other Substituted Phosphate Groups) metabolism, Antimitotic Agents pharmacology, Fatty Acids metabolism, Gangliosides metabolism, Glycosides pharmacology, Glycosphingolipids metabolism
- Abstract
Oleyl 2-acetamido-2-deoxy-α-D-glucopyranoside (1) was previously shown to exhibit antimitotic activity on glioma (C6) and melanoma (A375) cell lines. Preliminary studies about its mechanism of action using (1)H MAS NMR suggested that 1 may be altering the metabolism of lipids. We have now studied the effect of 1 on the fatty acid, sphingolipid and ganglioside content in a line of carcinomic human alveolar epithelial cells (A549) using UPLC-MS. Oleic acid and NB-DNJ were used as positive controls for inhibition of fatty acid and ganglioside synthesis, respectively. Compound 1 (10 μM) was more efficient than oleic acid in reducing fatty acid levels of A549 cells, producing a decrease in the range of 40-15%, depending on the acyl chain length and the number of insaturations. In addition, glycoside 1 caused a reduction on ganglioside content of A549 tumor cell line and accumulation of lactosylceramide, the common metabolic precursor for ganglioside biosynthesis. Alteration of ganglioside metabolism was also observed with two galactosylated derivatives of 1, which caused a more pronounced increase in lactosylceramide levels. Compound 1 at higher concentrations (above 30 μM) produced drastic alterations in glycosphingolipid metabolism, leading to cell metabolic profiles very different from those obtained at 10 μM. These biochemical changes were ascribed to activation of endoplasmic reticulum stress pathways.
- Published
- 2011
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.