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1.
Int J Pharm ; 419(1-2): 215-21, 2011 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-21864660

RESUMO

The hydration and swelling properties of the tablets made of chitosan, carboxymethyl starch, and a polyelectrolyte complex of these two polysaccharides have been studied by NMR imaging. We studied the effect of pH and ionic strength on the swelling of the tablets and on the diffusion of fluid into the tablets in water and simulated physiological fluids. The pH value of the fluids exerts a more significant effect than their ionic strengths on the swelling of the tablets. The tablets are compared also with those made of cross-linked high amylose starch. The formation of complex helps to keep the integrity of the tablets in various media and render a slow and restricted swelling similar to that of the tablets of the cross-linked high amylase starch, which is significantly lower than the swelling of chitosan and of carboxymethyl starch. The capacities to modulate the release rate of drugs in different media are discussed by comparing the matrices and evaluating the preparation process of the complex. A sustained release of less soluble drugs such as aspirin in gastrointestinal fluids can be provided by the complex, due to the ionic interaction and hydrogen bonding between the drug and the biopolymer complex.


Assuntos
Aspirina/administração & dosagem , Quitosana/química , Portadores de Fármacos/química , Amido/análogos & derivados , Amilose/química , Aspirina/química , Reagentes de Ligações Cruzadas/química , Preparações de Ação Retardada , Suco Gástrico/metabolismo , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Secreções Intestinais/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Concentração Osmolar , Solubilidade , Amido/química , Comprimidos , Água/química
2.
Neuroscience ; 167(3): 633-43, 2010 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-20188154

RESUMO

The cytoarchitectural organization of the nervous system depends partly on extracellular serine proteases, including reelin. This 400K protein, which also exists as the N-terminally-derived 300K and 180K fragments, acts through binding to the lipoprotein receptors apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor (VLDLR). Ceruloplasmin (CP), a multifunctional protein found in the circulation and also expressed on glial cells, was shown to bind to, and induce aggregation of neurons newly differentiated from P19 embryonic stem cells. This indicated a potential developmental role of CP in neuronal organization, possibly in relation with reelin and other extracellular serine proteases. Therefore, we analysed the effect of cell-impermeant, large spectrum, serine protease inhibitors on CP-induced neuroaggregation and studied reelin expression. Soybean trypsin inhibitor and aprotinin (SBTI+Apro) inhibited CP neuroaggregative action. Undifferentiated and neurally-differentiating cultures secreted the 400K reelin. The 180K fragment was present during and after differentiation whereas the 300K species was barely detectable. However, CP stimulated generation of the 300K in the differentiated neuronal cultures, and SBTI+Apro abolished this CP effect. Time course profiles and function-blocking antibody indicated that neuroaggregation does not depend on the generation of the 300K fragment or on reelin action. CP neuroaggregative action thus involves a pericellular serine protease, different from reelin. On the other hand, the CP stimulation of reelin cleavage is in line with a possible role of CP in nervous system development. Since P19 cells express ApoER2 and VLDLR, they can help understanding relationships existing between CP, reelin and intervening protease(s).


Assuntos
Ceruloplasmina/metabolismo , Neurônios/metabolismo , Serina Proteases/metabolismo , Animais , Moléculas de Adesão Celular Neuronais/antagonistas & inibidores , Moléculas de Adesão Celular Neuronais/metabolismo , Agregação Celular/efeitos dos fármacos , Agregação Celular/fisiologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Ceruloplasmina/farmacologia , Proteínas da Matriz Extracelular/antagonistas & inibidores , Proteínas da Matriz Extracelular/metabolismo , Proteínas Relacionadas a Receptor de LDL , Camundongos , Peso Molecular , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/metabolismo , Neurogênese/efeitos dos fármacos , Neurogênese/fisiologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Fragmentos de Peptídeos/efeitos dos fármacos , Fragmentos de Peptídeos/metabolismo , Estrutura Terciária de Proteína/efeitos dos fármacos , Estrutura Terciária de Proteína/fisiologia , Receptores de LDL/efeitos dos fármacos , Receptores de LDL/metabolismo , Receptores de Lipoproteínas/efeitos dos fármacos , Receptores de Lipoproteínas/metabolismo , Proteína Reelina , Serina Endopeptidases/metabolismo , Serina Proteases/efeitos dos fármacos , Inibidores de Serina Proteinase/farmacologia , Fatores de Tempo
3.
J Food Sci ; 73(5): C283-91, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18576971

RESUMO

This study focused on amino cross-linking as means of forming soy protein hydrogels with modifiable properties. The efficiency of glyceraldehyde, a potential food-grade cross-linking agent, was compared to glutaraldehyde, a well-known dialdehyde. The influence of the concentration of these agents on the degree of cross-linking as well as macroscopic and supramolecular properties was studied. The effect of increasing the cross-linker concentration was mainly an increase in degree of cross-linking and gel storage modulus (G') and a decrease in gel swelling ratio and increase in gel deswelling ratio. However, the cross-linking influence was less pronounced in the case of glyceraldehyde. Glutaraldehyde displayed greater ability to form hydrogels with modifiable properties. Finally, electron micrographs suggested that cross-linking agent type had no impact on gel microstructure.


Assuntos
Aminoácidos/química , Reagentes de Ligações Cruzadas/química , Glutaral/química , Gliceraldeído/química , Proteínas de Soja/química , Eletroforese em Gel de Poliacrilamida , Hidrogéis/química , Reologia , Proteínas de Soja/ultraestrutura
4.
Neuroscience ; 121(1): 73-82, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12946701

RESUMO

Ceruloplasmin (CP) is a copper-dependent ferroxidase. It regulates iron metabolism and is involved in inflammation, angiogenesis, and protection against oxidative stress. CP also modulates K(+) channel activity in neuroblastoma cells and affects cardiodynamics of isolated hearts. Considering the presence of CP in the nervous system and the importance of iron ions and K(+) channels in neuronal activity, we postulated a role of CP in neuronal development. This hypothesis was tested using the P19 mouse embryonal carcinoma cell line, a model of neuronal differentiation. Addition of CP to the culture medium of newly differentiated P19 neurons induced cell aggregation within 24 h. This effect was concentration-dependent half-maximal at 50 nM, and not associated with necrosis, apoptosis or changes in secretory function. Deglycosylated CP was aggregative but not denatured CP, copper salts, His(2)Cu complex, or other copper enzymes or serum proteins. CP-induced aggregation was less pronounced with aging neurons and seemed not to involve K(+) channels. Immunocytofluorescence analysis demonstrated that digoxigenin-labeled CP bound to P19 neurons and the proportion of responding neurons decreased with aging. The interaction of digoxigenin-labeled CP with neurons was half-maximal at 120 nM by enzyme-linked immunosorbent assay and displaced by unlabeled CP. Our data indicate a specific aggregative action of CP on young neurons in vitro, possibly involving CP receptors. A potential developmental role of CP in nervous system organization is thus demonstrated.


Assuntos
Diferenciação Celular/fisiologia , Ceruloplasmina/fisiologia , Neurônios/citologia , Neurônios/fisiologia , Animais , Agregação Celular/fisiologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Camundongos , Sistema Nervoso/citologia , Sistema Nervoso/enzimologia , Neurônios/enzimologia
5.
Inflammopharmacology ; 11(2): 155-63, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-15035817

RESUMO

Two contrasting topics are examined in this account: the protective actions of amine oxidases (AOs) resulting from the elimination and/or modulation of the levels of polyamines and some biogenic amines, such as histamine, in anaphylactic shock and the cell damaging effect of AOs catabolic products. Other functions of the plasma copper-containing amine oxidase are considered; namely the modification of some proteins by oxidation of their free amino groups, the auto-regulation of the catalytic activity of AOs, the protective effect against free radicals, and the regulation of K(+)-channels.

6.
Biochem Biophys Res Commun ; 288(4): 1006-10, 2001 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-11689010

RESUMO

Using SDS-PAGE and MALDI-TOF mass spectrometry, we investigated the difference in the molecular structure between human and bovine ceruloplasmin. In both cases, we found that the protein is present in two majors forms of different molecular mass. The difference between human and bovine ceruloplasmin was more obvious when characterized by MALDI-TOF than with the SDS-PAGE analysis. Furthermore, we established that the N-glycoside content of both enzymes is dissimilar and that the N-glycosyl moieties are distributed in a distinctive fashion in two glycoproteins. Finally, it appeared that both proteins exhibited different cleavage patterns after treatment with trypsin. This study indicates that human and bovine ceruloplasmin differ not only in sugar composition but also in primary structure.


Assuntos
Ceruloplasmina/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Amidoidrolases/metabolismo , Animais , Bovinos , Ceruloplasmina/metabolismo , Eletroforese em Gel de Poliacrilamida , Glicosilação , Humanos , Peso Molecular , Mapeamento de Peptídeos , Peptídeo-N4-(N-acetil-beta-glucosaminil) Asparagina Amidase , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismo , Tripsina/metabolismo
7.
J Control Release ; 76(1-2): 51-8, 2001 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-11532312

RESUMO

Selection of hydrogels as excipients in controlled drug release systems depends on the characteristics of the gel and of the drug. Three types of derivatives were synthesized from cross-linked high amylose starch (HASCL-6) by substitution of hydroxylic groups with cationic (carboxymethyl: CM), anionic (aminoethyl: AE) and acetate (Ac) groups. These new polymeric excipients are able to control the release over 20 h from monolithic tablets loaded with 20 to 60% drug. Three drugs were used as model tracer: acetaminophen (uncharged), acetylsalicylic acid (having an acidic group) and metformin (having a basic group). It was found that the release of ionic drugs from CM-HASCL-6 and AE-HASCL-6 matrices can be partially controlled by ionic interaction between pendant groups of polymer and drugs. The substitution degree of HASCL-6 derivatives can also be varied to modulate the drug's release time. These derivatives represent a novel generation of pharmaceutical excipients, recommended for high loading dosage formulations.


Assuntos
Sistemas de Liberação de Medicamentos , Excipientes/administração & dosagem , Amido/administração & dosagem , Acetaminofen/administração & dosagem , Acetaminofen/química , Amilose , Solubilidade
8.
Biochem Cell Biol ; 79(4): 489-97, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11527218

RESUMO

Ceruloplasmin (CP), an important serum antioxidant, is a blue copper glycoprotein with ferroxidase and oxidase activities. Among other physiological actions, plasma CP was shown to protect isolated rat hearts and cultured P19 neurons exposed to oxidative stress conditions, raising the possibility of using this protein in the treatment of cardiac and neuronal diseases related to oxidative damage. However, since therapeutic applications of CP must be compatible with restrictions in the administration of blood derivatives to humans, there is a need to produce the protein by genetic engineering. To help in the choice of adequate expression systems, we undertook this study to determine if the carbohydrate moiety on the protein is essential for its functions. CP was completely deglycosylated using N-glycosidase F under nondenaturing conditions. Deglycosylated CP was found to retain most of the conformational, antioxidant, and enzymatic properties of the native protein in vitro. Moreover, both forms of the protein had similar cardioprotective and neuronoprotective effects against oxidative stress as evaluated with isolated rat hearts undergoing ischemia-reperfusion and with cultured P19 neurons exposed to xanthine-xanthine oxidase. The data thus indicate that the carbohydrate moiety of CP is not essential for its enzymatic and protective actions. Accordingly, even the use of expression systems that do not glycosylate mammalian proteins could provide a recombinant CP that retains its therapeutic potential.


Assuntos
Antioxidantes/metabolismo , Cardiotônicos/metabolismo , Ceruloplasmina/metabolismo , Fármacos Neuroprotetores/metabolismo , Amidoidrolases/metabolismo , Linhagem Celular , Eletroforese em Gel de Poliacrilamida , Glicosilação , Estresse Oxidativo , Peptídeo-N4-(N-acetil-beta-glucosaminil) Asparagina Amidase
9.
J Agric Food Chem ; 49(3): 1397-403, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11312871

RESUMO

Sterilized biofilms based on soy protein isolate (SPI, S system) and a 1:1 mixture of SPI and whey protein isolate (WPI, SW system) were achieved through the formation of cross-links by means of gamma-irradiation combined with thermal treatments. The effect of the incorporation of carboxymethylcellulose (CMC) and poly(vinyl alcohol) was also examined. gamma-Irradiation combined with thermal treatment improved significantly the mechanical properties, namely, puncture strength and puncture deformation, for all types of films. Irradiated formulations that contain CMC behave more similarly as elastomers. CMC showed also significant improvements of the barrier properties, namely, water vapor permeability, for irradiated films of the S system and for non-irradiated films of the SW system.


Assuntos
Proteínas do Leite/química , Proteínas de Soja/química , Carboximetilcelulose Sódica/química , Raios gama , Temperatura Alta , Proteínas do Leite/efeitos da radiação , Álcool de Polivinil/química , Proteínas de Soja/efeitos da radiação , Proteínas do Soro do Leite
10.
J Agric Food Chem ; 48(11): 5566-75, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11087520

RESUMO

When cross-linked by heating or by gamma-irradiation and entrapped in cellulose, whey proteins can generate insoluble biofilms with good mechanical properties and high resistance to attack by proteolytic enzymes. Interchain cross-linking of proteins generated an increase in the puncture strength, and a decrease in water vapor permeability. Gelatin was added in film formulation as a stabilizer to improve the puncture strength and film appearance. The structure of the biofilms was also analyzed. SDS-PAGE revealed that heating and gamma-irradiation produce an increase of the molecular weight of the cross-linked protein. Size exclusion chromatography showed a molecular mass of 40 kDa for un-cross-linked whey proteins, whereas for the soluble fractions of the cross-linked proteins, molecular distributions were between 600 and 3800 kDa for the heated proteins and between 1000 and 2000 kDa for gamma-irradiated proteins. No major alteration of the structural conformation of the proteins was observed by FTIR for biofilms obtained after heat treatment, whereas gamma-irradiation induced some modifications in the protein structure. X-ray diffraction analysis suggests that cross-linking by gamma-irradiation seems to modify the conformation of proteins, which became more ordered and more stable.


Assuntos
Celulose/química , Proteínas do Leite/química , Biodegradação Ambiental , Reagentes de Ligações Cruzadas , Raios gama , Temperatura Alta , Proteínas do Leite/efeitos da radiação , Reologia , Termodinâmica , Proteínas do Soro do Leite
12.
Carbohydr Res ; 323(1-4): 163-75, 2000 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-10782298

RESUMO

Cross-linked high-amylose starch (CLHAS), obtained by high-amylose starch cross-linking, was recently introduced as an excipient (Contramid) for monolithic dosage forms that are able to control drug release over 18-24 h. These control properties are related to tablet swelling and are strongly dependent on the degree of the cross-linking of CLHAS. The permeability of solutes through CLHAS hydrogels depends on the chemical structure of the polymer. The aim of this study was to obtain a better understanding of how modifications in CLHAS molecular structures at the level of long-range and short-range order during the cross-linking and processing conditions relate to the release properties of the CLHAS matrices. Structural parameters such as crystallinity contribute significantly to the physical and mechanical aspects of starch products. X-ray diffractometry, FTIR spectroscopy, dissolution tests in vitro, and mechanical hardness (of dry tablets) were found to be sensitive to the cross-linking degree (cld) variation. Best release properties and highest mechanical hardness were obtained from CLHAS matrices with low-to-moderate crystallinity, where the V- and the B-type structures coexist with amorphous regions. X-ray and FTIR profiles of dry CLHAS powders were found to be predictive for release properties of CLHAS tablets.


Assuntos
Amilose/química , Reagentes de Ligações Cruzadas/química , Preparações de Ação Retardada , Cinética , Modelos Teóricos , Espectroscopia de Infravermelho com Transformada de Fourier , Relação Estrutura-Atividade , Fatores de Tempo , Difração de Raios X
13.
Br J Pharmacol ; 128(7): 1477-84, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10602326

RESUMO

1. This study was carried out to investigate novel cardioprotective effects of urea and the underlying mechanisms. The cardiac functions under oxidative stress were evaluated using Langendorff perfused isolated heart. 2. Isolated dogfish shark hearts tolerated the oxidative stress generated by electrolysis (10 mA, 1 min) of the perfusion solution (n=4), and also showed normal cardiac functions during post-ischaemia reperfusion (n=4). The high concentration of urea (350 mM) in the heart perfusate was indispensable for maintaining the normal cardiac functions of the shark heart. 3. Urea at 3 - 300 mM (n=4 for each group) protected the isolated rat heart against both electrolysis-induced heart damage and post-ischaemia reperfusion-induced cardiac injury. 4. A concentration-dependent scavenging effect of urea (3 - 300 mM, n=4 for each group) against electrolysis-induced reactive oxygen species was also demonstrated in vitro. 5. Urea derivatives as hydroxyurea, dimethylurea, and thiourea had antioxidant cardioprotective effect against the electrolysis-induced cardiac dysfunction of rat heart, but were not as effective as urea in suppressing the post-ischaemia reperfusion injury. 6. Our results suggest that urea and its derivatives are potential antioxidant cardioprotective agents against oxidative stress-induced myocardium damage including the post-ischaemia reperfusion-induced injury.


Assuntos
Coração/efeitos dos fármacos , Ureia/farmacologia , Animais , Cação (Peixe) , Eletrólise , Feminino , Técnicas In Vitro , Masculino , Metilaminas/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/metabolismo , Oxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Especificidade da Espécie , Ureia/sangue , Função Ventricular Esquerda/efeitos dos fármacos
14.
J Toxicol Environ Health A ; 57(7): 507-19, 1999 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-10494918

RESUMO

The adverse effects of heavy metal ions on the heart functions of lower vertebrates are largely unknown. In the present study, the effects of Cd2+, Cu2+, and Cu+ on the cardiac functions of the heart isolated from dogfish shark, Squalus acanthias, including the epicardial electrocardiogram, ventricular developed pressure (VDP), and heart beating rate, were studied. Cadmium (10 to 100 microM) significantly decreased VDP of the isolated shark hearts in a reversible manner. However, heart beating rate was not affected by cadmium. Cadmium also induced a transient modification of the amplitude and the form of the QRS complex. Cupric ion transiently increased VDP in a concentration-dependent manner, whereas cuprous ion (1 to 100 microM) did not markedly alter the cardiac functions of shark. Cupric or cuprous ions did not change heart beating rate and electrocardiogram at concentrations of 10 to 100 microM. Our results, for the first time, demonstrated the effects of cadmium on shark heart and indicated that the cardiac effects of copper are valence dependent. An elucidation of heavy metal effects on fish cardiac functions will help to understand the complex toxicological properties of heavy metals in different species and tissues, and will provide information for management of pollution control and marine resource protection.


Assuntos
Cloreto de Cádmio/toxicidade , Cobre/toxicidade , Cação (Peixe)/fisiologia , Poluentes Ambientais/toxicidade , Coração/efeitos dos fármacos , Animais , Eletrocardiografia , Coração/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Perfusão , Fatores de Tempo
15.
J Control Release ; 60(2-3): 161-7, 1999 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-10425322

RESUMO

An oral controlled release system based on direct compression of cross-linked amylose (CLA) and drug powders was previously introduced. For drugs with limited solubility or for some drugs for which solubility can be influenced by variation of gastro-intestinal pH, a system is required to accelerate drug release. This paper describes a novel enzymatically-controlled drug release (ECDR) system based on the addition of alpha-amylase to CLA tablets, which can modulate the release kinetics of drugs. The alpha-amylase within the tablets is able to hydrolyze alpha-1-4-glucosidic bonds present in the CLA semisynthetic substrate. Increasing amounts of alpha-amylase (5 to 25 EU) within the tablets induced a significant decrease in release time from 24 to 6 h. High amounts of external alpha-amylase (300-6000 EU/l) had a slight effect on the release rate. Drug release from the ECDR system seems to be controlled by two sequential mechanisms: (a) hydration and swelling of CLA tablets followed by (b) internal enzymatic hydrolysis of the hydrated gel phase.


Assuntos
Amilose/farmacocinética , Anti-Inflamatórios/farmacologia , alfa-Amilases/farmacologia , Amilose/química , Reagentes de Ligações Cruzadas/química , Preparações de Ação Retardada , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Hidrólise , Técnicas In Vitro , Comprimidos , Fatores de Tempo
16.
Biotechnol Appl Biochem ; 28 ( Pt 2): 99-104, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9756636

RESUMO

Preparative affinity chromatography of bovine serum amine oxidase (SAO) on aminohexyl (AH)-Sepharose was often associated with an unexpected irreversible SAO retention on the support. This particular enzyme immobilization, occurring without coupling reagents, was supposed to be due to a SAO ability to: (i) recognize alkylamine groups of the support as macro-molecularized substrate; (ii) catalyse their oxidation to the corresponding aldehydes, with release of NH3 and H2O2; and (iii) be immobilized on the activated support by a coupling between the nascent aldehyde groups and SAO free amine groups. This affinity immobilization procedure, with the self-activation of the support, being mild, allows by simple incubation for 24 h, the enzyme immobilization with the retention of 80% from original specific activity of free SAO. Immobilized SAO on AH-Sepharose microcolumns, viewed as a continuous flow-system reactor, was able to catalyse benzylamine oxidation for several weeks.


Assuntos
Amina Oxidase (contendo Cobre) , Cromatografia de Afinidade/métodos , Enzimas Imobilizadas/isolamento & purificação , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Sefarose/análogos & derivados , Animais , Benzilaminas/metabolismo , Bovinos , Fumaratos/metabolismo , Peróxido de Hidrogênio/metabolismo , Focalização Isoelétrica , Maleatos/metabolismo , Oxirredução , Peptídeos/metabolismo , Sefarose/metabolismo , Fatores de Tempo
17.
J Control Release ; 53(1-3): 225-34, 1998 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-9741930

RESUMO

Cross-linked high amylose starches have been developed as excipients for the formulation of controlled-release solid dosage forms for the oral delivery of drugs. Advantages of this new class of excipients include cost-effectiveness, readily accessible industrial manufacturing technology, high active ingredient core loading and the possibility of achieving a quasi zero-order release for most drugs. In addition to the latter, other features distinguish cross-linked high amylose starches from other excipients used to prepare hydrophilic matrices. Among these are the absence of erosion, the limited swelling and the fact that increasing cross-linking degrees results in increased water uptake rate, drug release rate and equilibrium swelling. Thus the goal of the present study was to gain some insights into the mechanism of drug release control by matrices of cross-linked high amylose starch. Water transport kinetics and dimensional changes were studied in matrices placed in water at 37 degrees C by an image analysis technique. The results show that in the first 5 min, a gel layer is formed at the surface of the tablet, after which the gel front seems to halt its progression toward the center of the tablet. Water continues to diffuse through the front and to invade the core. As a consequence, this latter swells, with a predominance for radial swelling. Equilibrium swelling is reached over 3 days, when the water concentration in the tablet becomes homogeneous and the whole tablet gelifies. Solid-state 13C-NMR were acquired on cross-linked high amylose starch powders, tablets and hydrated tablets with varying cross-linking degrees. They show a predominance of the V-type single helix arrangement of amylose in the dry state irrespective of the cross-linking degree. Upon hydration, the homologues with a low cross-linking degrees show a transition from the V to the B-type double helix arrangement. It is therefore hypothesized that the capacity of amylose to undergo the V to B transition is an important factor in controlling water transport and drug release rate. Finally applications to different drugs are reviewed briefly. They illustrate the versatility of this technology as generic versions of zero order OROS drug (Efidac) and Fickian release conventional matrices (Voltaren SR) were developed and successfully tested in pilot clinical studies to be bioequivalent to the references. These studies further showed that cross-linked high amylose starch matrices have the lowest inter-subject variability among the systems tested and show a total absence of food effect.


Assuntos
Amilose/administração & dosagem , Portadores de Fármacos , Administração Oral , Amilose/química , Reagentes de Ligações Cruzadas , Diclofenaco/administração & dosagem , Diclofenaco/sangue , Diclofenaco/farmacocinética , Efedrina/administração & dosagem , Efedrina/sangue , Efedrina/farmacocinética , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Valores de Referência
18.
Pigment Cell Res ; 11(2): 98-102, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9585247

RESUMO

It was shown that ceruloplasmin, apart from the known oxidative conversion of dopamine into melanin, can also produce (DHI)-melanin from 5,6-dihydroxyindole and THP-melanin from tetrahydropapaveroline. Ceruloplasmin acts as an oxidase and the kinetic parameters for these oxidative reactions are reported. Since these ceruloplasmin-catalyzed reactions occur also at pH 7.4, they could have a significant physiological impact. This ceruloplasmin-oxidasic activity is enhanced by copper ions and inhibited by chelators, such as ethylenediaminetetraacetic acid (EDTA) and desferoxamine (DEF). Some possible implication of melanin production in blood are discussed.


Assuntos
Ceruloplasmina/metabolismo , Melaninas/metabolismo , Quelantes , Cobre , Concentração de Íons de Hidrogênio , Oxirredução , Tetra-Hidropapaverolina/metabolismo
19.
Mol Cell Biochem ; 189(1-2): 127-35, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9879663

RESUMO

The chain-breaking antioxidant potential of caeruloplasmin and bovine serum albumin (BSA) has been investigated in comparison with other well-established antioxidants. Their Oxygen Radical Absorbing Capacity (ORAC), was measured by using beta-phycocyanin (beta-PC) as a fluorescent indicator protein, 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH) as a peroxyl radical generator and the water soluble vitamin E analogue, Trolox, as a reference standard. The relative peroxyl absorbing capacities/mole for Trolox, caeruloplasmin, heat-denatured caeruloplasmin (hCP), catalase, bovine serum albumin (BSA), superoxide dismutase (SOD), and deferoxamine were 1; 2.6; 3.3; 3.7; 1.2; 0.1; 0.2, respectively. Caeruloplasmin was far more effective as a peroxyl radical scavenger than SOD, deferoxamine and BSA, but slightly less effective than catalase. The peroxyl radical absorbing capacity of caeruloplasmin was enhanced by heat-denaturation of the protein. Electron paramagnetic resonance (EPR) spectroscopy using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin-trap, was applied in order to measure the scavenger abilities of caeruloplasmin on superoxide radical and hydroxyl radical production and the concentration required to inhibit by 50% oxygen free radical formation (IC50) was determined. The IC50 values of caeruloplasmin, hCP, and BSA for the superoxide radical were 12, 2, 260 microM and for the hydroxyl radical 15, 2, 200 microM. These results show that caeruloplasmin is an effective chain-breaking antioxidant for a variety of radicals, independently of its catalytic ferroxidase activity.


Assuntos
Antioxidantes/farmacologia , Ceruloplasmina/farmacologia , Catalase/química , Ceruloplasmina/química , Ceruloplasmina/metabolismo , Cromanos/química , Desferroxamina/química , Relação Dose-Resposta a Droga , Espectroscopia de Ressonância de Spin Eletrônica , Radicais Livres/química , Cinética , Ficocianina/análise , Espectrometria de Fluorescência , Detecção de Spin
20.
Arzneimittelforschung ; 46(9): 855-61, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8876933

RESUMO

The antioxidant effects of ceruloplasmin (CAS 9031-37-2) against oxygen free radicals (.O2-, .OH, 1O2) and their by-products (H2O2, HOCl), generated by electrolysis of Krebs-Henseleit buffer, were determined in vitro by the DPD (N,N-diethyl-p-phenylenediamine) colorimetric method and ex vivo by quantifying cardiodynamic variables of the isolated perfused rat heart. Purified ceruloplasmin (1 mumol/l) displayed a high antioxidant capacity in vitro (89.2%), while the scavenging capacity of superoxide dismutase (SOD) in equimolar concentrations was 38.1%. A relatively high scavenging activity (72.1%) was observed with bovine serum albumin (BSA). A control group of Langendorff isolated rat hearts (n = 8) was submitted to electrolysis (10 mA, for 1 min) without treatment, whereas the treated groups were perfused with ceruloplasmin, SOD or BSA (1 mumol/l) in the inflow cannula for 5 min before, during, and 5 min after electrolysis. The cardioprotective effect afforded by ceruloplasmin (83-89%) was higher than that observed with the same optimal dose of 1 mumol/l SOD (20-45%). With BSA, no protection was observed ex vivo. Particularities in scavenging specificities and mechanisms seem to explain the important differences between in vitro and ex vivo antioxidant capacities for these proteins.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Ceruloplasmina/química , Ceruloplasmina/farmacologia , Cardiopatias/prevenção & controle , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacologia , Superóxido Dismutase/química , Superóxido Dismutase/farmacologia , Animais , Eletrólise , Sequestradores de Radicais Livres/farmacologia , Cardiopatias/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Técnicas In Vitro , Masculino , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
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