18 results on '"Bernardo RR"'
Search Results
2. Therapeutic potential of low-cost nanocarriers produced by green synthesis: macrophage uptake of superparamagnetic iron oxide nanoparticles.
- Author
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Verçoza BR, Bernardo RR, Pentón-Madrigal A, Sinnecker JP, Rodrigues JC, and S de Oliveira LA
- Subjects
- Animals, Drug Delivery Systems, Ferric Compounds pharmacokinetics, Green Chemistry Technology economics, Hyperthermia, Induced methods, Magnetite Nanoparticles analysis, Magnetite Nanoparticles ultrastructure, Mice, RAW 264.7 Cells, Ferric Compounds therapeutic use, Green Chemistry Technology methods, Macrophages metabolism, Magnetite Nanoparticles therapeutic use
- Abstract
Aim: The primary goal of this work was to synthesize low-cost superparamagnetic iron oxide nanoparticles (SPIONs) with the aid of coconut water and evaluate the ability of macrophages to internalize them. Our motivation was to determine potential therapeutic applications in drug-delivery systems associated with magnetic hyperthermia. Materials & methods: We used the following characterization techniques: x-ray and electron diffractions, electron microscopy, spectrometry and magnetometry. Results: The synthesized SPIONs, roughly 4 nm in diameter, were internalized by macrophages, likely via endocytic/phagocytic pathways. They were randomly distributed throughout the cytoplasm and mainly located in membrane-bound compartments. Conclusion: Nanoparticles presented an elevated intrinsic loss power value and were not cytotoxic to mammalian cells. Thus, we suggest that low-cost SPIONs have great therapeutic potential.
- Published
- 2019
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3. Platelet activating factor blocks interkinetic nuclear migration in retinal progenitors through an arrest of the cell cycle at the S/G2 transition.
- Author
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Fragel-Madeira L, Meletti T, Mariante RM, Monteiro RQ, Einicker-Lamas M, Bernardo RR, Lopes AH, and Linden R
- Subjects
- Animals, Biological Transport, Cell Proliferation, Checkpoint Kinase 1, Extracellular Signal-Regulated MAP Kinases, Protein Kinases, Rats, Retina cytology, Stem Cells, p38 Mitogen-Activated Protein Kinases, Cell Nucleus physiology, G2 Phase, Platelet Activating Factor physiology, Platelet Membrane Glycoproteins physiology, Receptors, G-Protein-Coupled physiology, S Phase
- Abstract
Nuclear migration is regulated by the LIS1 protein, which is the regulatory subunit of platelet activating factor (PAF) acetyl-hydrolase, an enzyme complex that inactivates the lipid mediator PAF. Among other functions, PAF modulates cell proliferation, but its effects upon mechanisms of the cell cycle are unknown. Here we show that PAF inhibited interkinetic nuclear migration (IKNM) in retinal proliferating progenitors. The lipid did not, however, affect the velocity of nuclear migration in cells that escaped IKNM blockade. The effect depended on the PAF receptor, Erk and p38 pathways and Chk1. PAF induced no cell death, nor a reduction in nucleotide incorporation, which rules out an intra-S checkpoint. Notwithstanding, the expected increase in cyclin B1 content during G2-phase was prevented in the proliferating cells. We conclude that PAF blocks interkinetic nuclear migration in retinal progenitor cells through an unusual arrest of the cell cycle at the transition from S to G2 phases. These data suggest the operation, in the developing retina, of a checkpoint that monitors the transition from S to G2 phases of the cell cycle.
- Published
- 2011
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4. Cardiolipin, a lipid found in mitochondria, hydrogenosomes and bacteria was not detected in Giardia lamblia.
- Author
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Rosa Ide A, Einicker-Lamas M, Bernardo RR, and Benchimol M
- Subjects
- Amino Acid Sequence, Animals, Cardiolipins isolation & purification, Chromatography, High Pressure Liquid, Chromatography, Thin Layer, Conserved Sequence, Giardia lamblia enzymology, Iodine, Lipids isolation & purification, Membrane Proteins analysis, Membrane Proteins chemistry, Mycoplasma penetrans enzymology, Organelles chemistry, Organelles enzymology, Saccharomyces cerevisiae enzymology, Sequence Alignment, Transferases (Other Substituted Phosphate Groups) analysis, Transferases (Other Substituted Phosphate Groups) chemistry, Cardiolipins analysis, Giardia lamblia chemistry, Mitochondria chemistry
- Abstract
Giardia lamblia is a protozoan parasite with many characteristics common among eukaryotic cells, but lacking other features found in most eukaryotes. Cardiolipin is a phospholipid located exclusively in energy transducing membranes and it was identified in mitochondria, bacteria, hydrogenosomes and chloroplasts. In eukaryotes, cardiolipin is the only lipid that is synthesized in the mitochondria. Biochemical procedures (TLC, HPLC) and fluorescent tools (NAO) were applied in order to search for cardiolipin in G. lamblia. In addition, BLAST searches were used to find homologs of enzymes that participate in the cardiolipin synthesis. Cardiolipin synthase was searched in the Giardia genome, using Saccharomyces cerevisiae and Mycoplasma penetrans sequences as bait. However, a good match to G. lamblia related proteins was not found. Here we show that mitosomes of G. lamblia apparently do not contain cardiolipin, which raises the discussion for its endosymbiotic origin and for the previous proposal that Giardia mitosomes are modified mitochondria.
- Published
- 2008
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- View/download PDF
5. FML vaccine against canine visceral leishmaniasis: from second-generation to synthetic vaccine.
- Author
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Palatnik-de-Sousa CB, Barbosa Ade F, Oliveira SM, Nico D, Bernardo RR, Santos WR, Rodrigues MM, Soares I, and Borja-Cabrera GP
- Subjects
- Adjuvants, Immunologic pharmacology, Animals, Brazil, Dog Diseases parasitology, Dog Diseases prevention & control, Dogs, Humans, Leishmania donovani immunology, Leishmaniasis, Visceral prevention & control, Saponins pharmacology, Vaccines, DNA immunology, Leishmaniasis Vaccines immunology, Leishmaniasis, Visceral veterinary, Vaccines, Synthetic microbiology
- Abstract
The Leishmania donovani glycoprotein fraction, known as FML, successfully underwent preclinical and clinical (Phase I-III) vaccine trials against canine visceral leishmaniasis (92-95% of protection and 76-80% of vaccine efficacy) when formulated with a QS21 saponin-containing adjuvant. It became the licensed Leishmune vaccine for canine prophylaxis in Brazil. The immune response raised by the vaccine is long lasting, immunotherapeutic and reduces dog infectivity blocking the transmission of the disease, as revealed by an in vivo assay. The preliminary epidemiological control data of vaccinated areas in Brazil indicate that, in spite of the still low vaccine coverage, there was a significant decrease in the incidence of the human and canine disease. A 36-kDa glycoprotein, in the FML complex, is the human marker of the disease, which was protective in mice as native recombinant protein or DNA vaccine. The DNA vaccine is now being tested against the canine disease. This review resumes the development of the second-generation FML-saponin-Leishmune vaccine, its adjuvant and of the NH36 DNA vaccine, toward the identification of its major epitopes that might be included in a possible future synthetic vaccine.
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- 2008
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6. Occurrence of toxin-producing cyanobacteria blooms in a Brazilian semiarid reservoir.
- Author
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Costa IA, Azevedo SM, Senna PA, Bernardo RR, Costa SM, and Chellappa NT
- Subjects
- Aphanizomenon metabolism, Bacterial Toxins biosynthesis, Brazil, Chromatography, High Pressure Liquid, Cylindrospermopsis metabolism, Environmental Monitoring methods, Enzyme-Linked Immunosorbent Assay, Microcystis metabolism, Population Density, Seasons, Aphanizomenon isolation & purification, Bacterial Toxins analysis, Cylindrospermopsis isolation & purification, Microcystis isolation & purification, Water Microbiology
- Abstract
We report the occurrence of cyanobacterial blooms and the presence of cyanotoxins in water samples from the Armando Ribeiro Gonçalves reservoir (06 degrees 08 S and 37 degrees 07 W), located in the state of Rio Grande do Norte, in the semiarid region of northeastern Brazil. The cyanobacterial species were identified and quantified during the rainy and dry seasons in the year 2000. Cyanotoxins such as microcystins, saxitoxins and cylindrospermopsins were analyzed and quantified using HPLC and ELISA methods. The mixed toxic blooms of Cylindrospermopsis raciborskii, Microcystis spp (M. panniformis, M. protocystis, M. novacekii) and Aphanizomenon spp (Aphanizomenon gracile, A. cf. manguinii, A. cf. issastschenkoi) were persistent and represented 90-100% of the total phytoplankton species. Toxic cyanobacterial blooms from the Armando Ribeiro Gonçalves reservoir were analyzed and found to have three phases in relation to the annual cycle. During the rainy season, an intense toxic bloom of Cylindrospermopsis raciborskii was recorded along with saxitoxins (3.14 microg.L(-1)). During the transition period, between the rainy and dry seasons, different species of Microscytis occurred and microcystin as high as 8.8 microg.L(-1) was recorded. In the dry season, co-dominance of Cylindrospermopsis raciborskii, Microcystis spp and Aphanizomenon spp occurred and the concentrations of saxitoxin remained very low. Our results indicate the presence of microcystins (8.8 microg.L(-1)) and saxitoxins (3.14 microg.L(-1)) into the crude water, with increasing concentrations from the second fortnight of April to late May 2000. The occurrence of toxic blooms in this reservoir points to a permanent risk of cyanotoxins in supply waters, indicating the need for the implementation of bloom control measures to improve the water quality. Exposure of the local population to cyanotoxins through their potential accumulation in fish muscle must also be considered.
- Published
- 2006
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7. Diacylglycerol kinase activity in purified basolateral membranes of kidney tubules. I. Evidence for coupling with phospholipase C.
- Author
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Nogaroli L, Silva OF, Bonilha TA, Moreno PA, Bernardo RR, Vieyra A, and Einicker-Lamas M
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- Adenosine Triphosphate metabolism, Basement Membrane enzymology, Catalysis drug effects, Diglycerides metabolism, Estrenes pharmacology, Humans, Isoenzymes chemistry, Isoenzymes metabolism, Magnesium metabolism, Phosphatidic Acids metabolism, Phosphodiesterase Inhibitors pharmacology, Pyrrolidinones pharmacology, Signal Transduction drug effects, Cell Membrane enzymology, Diacylglycerol Kinase chemistry, Diacylglycerol Kinase metabolism, Kidney Tubules, Proximal enzymology, Type C Phospholipases metabolism
- Abstract
The diacylglycerol kinase (DGK) catalyzes the phosphorylation of diacylglycerol (DAG) yielding phosphatidic acid (PA) signaling molecules which are involved in the modulation of different cell responses. The aim of this work was to characterize the DGK activity associated to the basolateral membranes (BLM) of kidney proximal tubules, in a native preparation that preserves the membrane microenvironment. The Arrhenius plot of DGK activity was non-linear, indicating a complex influence of the lipid environment of the native membrane. The formation of PA was strongly impaired by U73122, an inhibitor of PLC, whereas remained unmodified when exogenous DAG or PLC were added. The Mg.ATP2- complex is the true phosphoryl-donor substrate, and the very narrow peak of activation at pH 7.0 suggests that amino acids that dissociate at this pH, i.e. hystidine residues, play a role by acting in the coordination of the Mg2+ atoms. The renal DGK is almost completely blocked by 0.1 mM sphingosine, but it is insensitive to micromolar free Ca2+ concentrations and to R59499, the most potent inhibitor of the classical DGKs. Taken as a whole, these data suggest that the DGK isoform present in BLM of proximal tubules is different from those included in the type I family, and that membranous PLC could be the main source of DAG for DGK catalysis.
- Published
- 2005
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8. Sphingosine-1-phosphate formation activates phosphatidylinositol-4 kinase in basolateral membranes from kidney cells: crosstalk in cell signaling through sphingolipids and phospholipids.
- Author
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Einicker-Lamas M, Wenceslau LD, Bernardo RR, Nogaroli L, Guilherme A, Oliveira MM, and Vieyra A
- Subjects
- Animals, Chromatography, High Pressure Liquid, Chromatography, Thin Layer, Cytosol metabolism, Dose-Response Relationship, Drug, Edetic Acid, Kidney metabolism, Kinetics, Magnesium chemistry, Phospholipids metabolism, Phosphorylation, Rats, Signal Transduction, Sphingolipids metabolism, Sphingosine analogs & derivatives, Swine, Time Factors, 1-Phosphatidylinositol 4-Kinase metabolism, Cell Membrane metabolism, Kidney cytology, Lysophospholipids metabolism, Phosphotransferases (Alcohol Group Acceptor) metabolism, Sphingosine metabolism
- Abstract
Sphingosine-1-phosphate (S1P) and phosphatidylinositol-4 phosphate [PtdIns(4)P] are important second messengers in various cellular processes. Here, we show that S1P and PtdIns(4)P are formed in purified basolateral membranes (BLM) derived from kidney proximal tubules, indicating the presence of a plasma membrane associated SPK (BLM-SPK) and phosphatidylinositol-4 kinase (PI-4K). We observed that S1P synthesis is linear with time, dependent on protein concentration, and saturable in the presence of increasing concentrations of sphingosine. Different from the observations on cytosolic SPKs, the formation of S1P by BLM-SPK is Mg(2+)-independent and insensitive to the classical inhibitor of the cytosolic SPKs, DL-threo-dihydrosphingosine. With sphingosine as substrate, the enzyme shows cooperative kinetics (n = 3.4) with a K(0.5) value of 0.12 mM, suggesting that BLM-SPK is different from the previously characterized cytosolic SPK. The formation of PtdIns(4)P markedly inhibits BLM-SPK activity. Conversely, a strong activation of PtdIns(4)P synthesis by the formation of S1P is observed. Taken together, these results indicate that (i) basolateral membranes from kidney cells harbor a SPK activity that potentially regulates renal epithelium function, and (ii) the formation of S1P mediated by SPK enhances PI-4K activity, while PtdIns(4)P in turn inhibits SPK, suggesting an interplay between these lipid signaling molecules. These findings suggest the possibility of crosstalk between sphingolipids and glycerolipids, which might be involved in the regulation of transepithelial fluxes across the BLM of kidney cells.
- Published
- 2003
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9. Saponins, IL12 and BCG adjuvant in the FML-vaccine formulation against murine visceral leishmaniasis.
- Author
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Santos WR, de Lima VM, de Souza EP, Bernardo RR, Palatnik M, and Palatnik de Sousa CB
- Subjects
- Adjuvants, Immunologic administration & dosage, Animals, Liver parasitology, Mice, Mycobacterium bovis, Protozoan Vaccines administration & dosage, Protozoan Vaccines immunology, Antigens, Protozoan immunology, Interleukin-12 therapeutic use, Leishmania donovani immunology, Leishmaniasis, Visceral prevention & control, Saponins therapeutic use
- Abstract
The FML antigen of Leishmania donovani, in combination with either Riedel de Haën (R), QuilA, QS21 saponins, IL12 or BCG, was used in vaccination of an outbred murine model against visceral leishmaniasis (VL). Significant and specific increases in anti-FML IgG and IgM responses were detected for all adjuvants, and in anti-FML IgG1, IgG2a and IgG2b and delayed type of hypersensitivity to L. donovani lysate (DTH), only for all saponins and IL12. The QS21-FML and QuilA-FML groups achieved the highest IgG2a response. QuilA-FML developed the strongest DTH and QS21-FML animals showed the highest serum IFN-gamma concentrations. The reduction of parasitic load in the liver in response to each FML-vaccine formulation was: 52% (P<0.025) for BCG-FML, 73% (P<0.005) for R-FML, 93% (P<0.005) for QuilA-FML and 79.2% (P<0.025) for QS21-FML treated animals, respectively. Protection was specific for R-FML and QS21-FML while the QuilA saponin treatment itself induced 69% of LDU reduction. The FML-saponin vaccines promote significant, specific and strong protective effects against murine visceral leishmaniasis. BCG-FML induced minor and non-specific protection while IL12-FML, although enhancing the specific antibody and IDR response, failed to reduce the parasitic load of infected animals.
- Published
- 2002
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10. Vaccination of Balb/c mice against experimental visceral leishmaniasis with the GP36 glycoprotein antigen of Leishmania donovani.
- Author
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Paraguai de Souza E, Bernardo RR, Palatnik M, and Palatnik de Sousa CB
- Subjects
- Animals, Antibodies, Protozoan biosynthesis, Antigens, Protozoan isolation & purification, Female, Immunity, Cellular, Mice, Mice, Inbred BALB C, Protozoan Proteins administration & dosage, Protozoan Proteins immunology, Protozoan Proteins isolation & purification, Antigens, Protozoan administration & dosage, Leishmania donovani immunology, Leishmaniasis, Visceral immunology, Leishmaniasis, Visceral prevention & control, Protozoan Vaccines administration & dosage
- Abstract
Leishmania donovani GP36 glycoprotein is the main antigen of the FML Fucose Mannose Ligand (FML) complex specifically recognized by sera of kala-azar human patients. The GP36 was isolated by chemical elution + sonication and used for Balb/c mouse vaccination in combination with saponin, by the s.c. route, inducing a strong and specific protective effect against experimental visceral leishmaniasis shown by the increase of: specific IgG antibodies (82.6%), mainly IgG2a, the delayed type of hypersensitivity to promastigote lysate (37.8%, P < 0.001), the in vitro cellular proliferative response to GP36 of ganglia lymphocytes (53.5%, P < 0.005) and the decrease of liver parasite burden (68.1%, P < 0.025). Saponin treated controls reacted significantly differently from GP36 vaccinated animals at all the assayed variables (P < 0.05). GP36 induced significant protection against murine visceral leishmaniasis at concentrations commonly used for vaccination with recombinant antigens.
- Published
- 2001
- Full Text
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11. Flavonol glycosides from Costus spicatus.
- Author
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da Silva BP, Bernardo RR, and Parente JP
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- Animals, Anti-Inflammatory Agents, Non-Steroidal isolation & purification, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Chromatography, High Pressure Liquid, Disaccharides isolation & purification, Disaccharides pharmacology, Flavonoids isolation & purification, Flavonoids pharmacology, Flavonols, Glycosides isolation & purification, Glycosides pharmacology, In Vitro Techniques, Macrophages, Peritoneal drug effects, Macrophages, Peritoneal metabolism, Male, Mice, Mice, Inbred BALB C, Nitric Oxide antagonists & inhibitors, Nitric Oxide biosynthesis, Plant Leaves chemistry, Quercetin chemistry, Quercetin isolation & purification, Quercetin pharmacology, Anti-Inflammatory Agents, Non-Steroidal chemistry, Disaccharides chemistry, Flavonoids chemistry, Glycosides chemistry, Kaempferols, Plants, Medicinal chemistry, Quercetin analogs & derivatives
- Abstract
Two flavonol diglycosides, tamarixetin 3-O-neohesperidoside, kaempferide 3-O-neohesperidoside and the known quercetin 3-O-neohesperidoside, together with six other known flavonoids were isolated from the leaves of Costus spicatus and their structures were elucidated by a combination of spectroscopic and chemical methods. The flavonol diglycosides were evaluated for inhibitory activity of nitric oxide production by activated macrophages (Fig. 1).
- Published
- 2000
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12. A furostanol glycoside from rhizomes of Costus spicatus.
- Author
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Da Silva BP, Bernardo RR, and Parente JP
- Subjects
- Carbohydrate Conformation, Carbohydrate Sequence, Magnetic Resonance Spectroscopy, Mass Spectrometry, Molecular Sequence Data, Saponins chemistry, Saponins isolation & purification, Plants, Medicinal chemistry, Steroids
- Abstract
A new furostanol glycoside was isolated from the rhizomes of Costus spicatus. Its structure was established as (3 beta,22 alpha,25R)-26-(beta -D-glucopyranosyloxy)-22-methoxyfurost-5-en-3-yl O-D-apio-beta-D-furanosyl-(1-->2)-O-[6-deoxy-alpha-L-mannopyranosy l-(1-->4)]- beta-D-glucopyranoside. The structural identification was performed using detailed analysis of 1H and 13C NMR spectra including 2D NMR spectroscopic techniques (COSY, HETCOR and COLOC) and chemical conversions.
- Published
- 1999
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13. A new steroidal saponin from the rhizomes of Costus spicatus.
- Author
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da Silva BP, Bernardo RR, and Parente JP
- Subjects
- Carbohydrate Sequence, Molecular Sequence Data, Molecular Structure, Saponins chemistry, Spectrum Analysis, Plants, Medicinal chemistry, Saponins isolation & purification, Steroids
- Abstract
A new steroidal saponin has been isolated from the rhizomes of Costus spicatus and its structure was elucidated as (3 beta, 22 alpha, 25R) -26-(beta-D-glucopyranosyloxy)-2-methoxyfurost-5-en-3-yl O-D-apio-beta-D-furanosyl-(1-->4)-O-[alpha-L-rhamnopyranosyl-(1--> 2)]- beta-D-glucopyranoside by means of IR, MS, NMR and chemical evidence.
- Published
- 1999
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14. Cyclosporin A and trifluoperazine, two resistance-modulating agents, increase ivermectin neurotoxicity in mice.
- Author
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Marques-Santos LF, Bernardo RR, de Paula EF, and Rumjanek VM
- Subjects
- Animals, Brain Chemistry drug effects, Chromatography, High Pressure Liquid, Drug Interactions, Female, Ivermectin administration & dosage, Ivermectin pharmacokinetics, Ivermectin pharmacology, Mice, Time Factors, ATP Binding Cassette Transporter, Subfamily B chemistry, Blood-Brain Barrier drug effects, Cyclosporine pharmacology, Drug Resistance, Multiple genetics, Ivermectin toxicity, Trifluoperazine pharmacology
- Abstract
The P-glycoprotein expressed in the blood-brain barrier has been associated with the restricted access of many compounds to the central nervous system. Mice lacking the mdr1a P-glycoprotein gene show an accumulation of various drugs in brain tissues. P-glycoprotein is also correlated with the phenomenon of multidrug resistance in tumour cells. To investigate the effects of drugs that modulate multidrug resistance in the selective permeability of the blood-brain barrier, mice were treated with cyclosporin A or trifluoperazine plus ivermectin, a P-glycoprotein substrate, that has a limited access to the central nervous system. When mice received an injection of cyclosporin A (50 mg/kg, intraperitoneally) or trifluoperazine (750 microg/kg, intraperitoneally) one hour prior to the administration of ivermectin (10-15 mg/kg, intraperitoneally) there was an increase in the acute toxicity of ivermectin. HPLC analysis of brain tissues indicated that the ivermectin brain concentration was 2.5 times higher when mice were previously treated with cyclosporin A (50 mg/kg). These results suggest that attention should be given to the side effects of drugs that interact with P-glycoprotein and are commonly used clinically and also to the possibility of creating a pharmacological gap in the blood-brain barrier that allows the access of chemotherapeutic drugs to brain tumours.
- Published
- 1999
- Full Text
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15. Rotenoids from roots of Clitoria Fairchildiana.
- Author
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Silva BP, Bernardo RR, and Parente JP
- Abstract
A new rotenoid, named 9-demethylclitoriacetal, together with the known compounds, 11-deoxyclitoriacetal, 6-deoxyclitoriacetal, clitoriacetal and stemonal, was isolated from roots of Clitoria fairchildiana. Its structure was elucidated as 6a,12a-dihydro-6,9,11,12a-tetrahydroxy-2,3-dimethoxy-[1]benzopyrano[3,4-b] [1]benzopyran-12(6H)-one (1), on the basis of spectroscopic and chemical evidence.
- Published
- 1998
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16. A new rotenoid glucoside, 6-deoxyclitoriacetal 11-O-beta-D-gluco-pyranoside, from the roots of Clitoria fairchildiana.
- Author
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Silva BP, Bernardo RR, and Parente JP
- Published
- 1998
- Full Text
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17. Haemolytic activities of plant saponins and adjuvants. Effect of Periandra mediterranea saponin on the humoral response to the FML antigen of Leishmania donovani.
- Author
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Santos WR, Bernardo RR, Peçanha LM, Palatnik M, Parente JP, and Palatnik de Sousa CB
- Subjects
- Adult, Animals, Antibodies, Protozoan biosynthesis, Antibodies, Protozoan drug effects, Antibodies, Protozoan immunology, Cricetinae, Fucose metabolism, Humans, Lectins toxicity, Leishmaniasis, Visceral immunology, Leishmaniasis, Visceral prevention & control, Ligands, Mannose metabolism, Mice, Mice, Inbred BALB C, Plant Extracts toxicity, Saponins toxicity, Adjuvants, Immunologic toxicity, Antigens, Protozoan immunology, Fucose immunology, Hemolysin Proteins toxicity, Lectins immunology, Leishmania donovani immunology, Mannose immunology, Saponins immunology
- Abstract
An 87.7% (P < 0.01) and 84% (P < 0.001) of protection against visceral leishmaniasis was achieved in CB hamsters and Balb/c mice, respectively, with saponin combined to the fucose-mannose ligand of Leishmania donovani (FML). However, an undesirable haemolytic effect was described for several saponins. Aiming to improve the formulation with FML/saponin, we comparatively analysed the haemolytic potential of recently characterized plant saponins and currently used adjuvants. The haemolytic activity of steroidic saponins from Agave sisalana; Smilax officinalis as well as commercial saponin (Riedel De Haën's), was higher than that of triterpenoid ones (Bredemeyera floribunda; Periandra mediterranea) and the Freund's complete adjuvant. The concentration resulting in 50% haemolysis was 500 micrograms ml-1 for aluminum hydroxide. The low haemolytic effect of P. mediterranea saponin was abolished by removal of its glycidic moiety and its sapogenin fraction as well as the Freund's Incomplete Adjuvant were non-haemolytic within this range. Furthermore, the adjuvant effect of three doses of P. mediterranea saponin injected with the FML antigen of L. donovani, was assayed in mice, either by the intraperitoneal (i.p.) or the subcutaneous (s.c.) route. The anti-FML IgG antibody levels increased and detectable levels were observed up to 3 months in the s.c. group. The response was expanded in both groups after an injection with a fourth vaccine dose. The IgG response showed increased levels of IgG2a only in the i.p. group, while IgG2b and IgG1 but not IgG3 antibodies were higher than controls in both groups. In conclusion, the results suggest that the recently described triterpenoid fractions of P. mediterranea can be safely used as adjuvant with low or non-haemolytic effect.
- Published
- 1997
- Full Text
- View/download PDF
18. Steroidal saponins from Smilax officinalis.
- Author
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Bernardo RR, Pinto AV, and Parente JP
- Subjects
- Carbohydrate Conformation, Carbohydrate Sequence, Carbohydrates analysis, Magnetic Resonance Spectroscopy, Medicine, Traditional, Molecular Sequence Data, Molecular Structure, Saponins isolation & purification, Steroids isolation & purification, Plants, Medicinal, Saponins chemistry, Steroids chemistry
- Abstract
Three new steroidal saponins were isolated from the rhizomes of Smilax officinalis. The structures of these saponins were established by extensive spectral data, hydrolysis and chemical correlation as sarsasapogenin 3-O-beta-D-glucopyranosyl-(1-->4)-[alpha-L-arabinopyranosyl-(1-->6 )-beta- D-glucopyranoside, neotigogenin 3-O-beta-D-glucopyranosyl-(1-->4)-[alpha-L-arabinopyranosyl-(1-->6 )]-beta- D-glucopyranoside and 25S-spirostan-6 beta-ol 3-O-beta-D-glucopyranosyl-(1-->4)-[alpha-L-arabinopyranosyl-(1-->6 )]-beta- D-glucopyranoside. Acid hydrolysis of the latter compound gave a sapogenin which has a new orientation of an hydroxyl on the steroidal skeleton. A route is proposed for the biogenesis of the latter sapogenin which is an uncommon steroidal aglycone.
- Published
- 1996
- Full Text
- View/download PDF
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