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1.
ScientificWorldJournal ; 2014: 507351, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25133239

RESUMO

A lasting dream of human beings is to reverse or postpone aging. In this study, dimethylaminoethanol (DMAE) and compound amino acid (AA) in Mesotherapy were investigated for their potential antiaging effects on D-galactose induced aging skin. At 18 days after D-gal induction, each rat was treated with intradermal microinjection of saline, AA, 0.1% DMAE, 0.2% DMAE, 0.1% DMAE + AA, or 0.2% DMAE + AA, respectively. At 42 days after treatment, the skin wound was harvested and assayed. Measurement of epidermal and dermal thickness in 0.1% DMAE + AA and 0.2% DMAE + AA groups appeared significantly thicker than aging control rats. No differences were found in tissue water content among groups. Hydroxyproline in 0.1% DMAE + AA, 0.2% DMAE + AA, and sham control groups was much higher than all other groups. Collagen type I, type III, and MMP-1 expression was highly upregulated in both 0.1% DMAE + AA and 0.2% DMAE + AA groups compared with aging control. In contrast, TIMP-1 expression levels of various aging groups were significantly reduced when compared to sham control. Coinjection of DMAE and AA into target tissue has marked antiaging effects on D-galactose induced skin aging model of rat.


Assuntos
Aminoácidos/farmacologia , Deanol/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Animais , Colágeno/genética , Colágeno/metabolismo , Galactose/farmacologia , Masculino , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Ratos , Ratos Wistar , Pele/metabolismo , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo
2.
Eksp Klin Farmakol ; 75(4): 17-9, 2012.
Artigo em Russo | MEDLINE | ID: mdl-22702105

RESUMO

Experiments on mice with streptozotocin-induced diabetes mellitus and stress-induced erosive ulcerous damage of the mucous membrane of stomach showed evidence of the preventive activity of deanol aceglumate in the course of peroral introduction at a dose of 250 mg/kg per 24 h during 4 days. This effect is accompanied by activation of the peristalsis of bowels and by an increase in the blood flow in the wall of stomach.


Assuntos
Antidiscinéticos/farmacologia , Deanol/farmacologia , Diabetes Mellitus Experimental/prevenção & controle , Úlcera Gástrica/prevenção & controle , Estresse Fisiológico , Animais , Diabetes Mellitus Experimental/fisiopatologia , Camundongos , Peristaltismo/efeitos dos fármacos , Estômago/irrigação sanguínea , Estômago/fisiopatologia , Úlcera Gástrica/fisiopatologia
3.
Drug Metab Lett ; 6(1): 54-9, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22300295

RESUMO

Recently, a number of synthetic drugs used in a variety of therapeutic indications have been reported to have antiaging effects. Among them, Dimethylaminoethanol (DMAE), an anologue of dietylaminoethanol, is a precursor of choline, which in turn allows the brain to optimize the production of acetylcholine that is a primary neurotransmitter involved in learning and memory. The data presented here includes new information on the ability of the compound to scavenge specific free radicals, assessed by Electron Spectroscopic Resonance (EPR), to further analyze the role of DMAE as an antioxidant. DMAE ability to directly react with hydroxyl, ascorbyl and lipid radicals was tested employing in vitro assays, and related to the supplemented dose of the compound.


Assuntos
Antioxidantes/farmacologia , Deanol/farmacologia , Sequestradores de Radicais Livres/farmacologia , Animais , Antioxidantes/administração & dosagem , Deanol/administração & dosagem , Ácido Desidroascórbico/análogos & derivados , Ácido Desidroascórbico/metabolismo , Relação Dose-Resposta a Droga , Espectroscopia de Ressonância de Spin Eletrônica , Sequestradores de Radicais Livres/administração & dosagem , Radicais Livres/metabolismo , Radical Hidroxila/metabolismo , Microssomos Hepáticos/metabolismo , Ratos
4.
Braz. j. pharm. sci ; 46(4): 705-713, Oct.-Dec. 2010. ilus, graf, tab
Artigo em Inglês | LILACS | ID: lil-622870

RESUMO

DMAE glycolate (DG) and sunscreens have been used associated in anti-aging dermocosmetic formulations. Despite extensive use of these substances, methods for quantification of DG as raw material and in cosmetic formulations, especially when associated, are not described in the literature. RP-HPLC and non-aqueous titration methods, with determination potentiometric end-point (PT), were developed and validated for rapid assay of DG as raw material and in a topic emulsion in association with sunscreens. Both methods are simple, selective, linear, accurate and precise. The PT method was chosen for stability study of DG in the formulation developed. The proposed formulation presented good stability performance as regards aspect, pH, apparent viscosity, and SPF, with less than 5% of DG degradation compared to initial conditions.


Glicolato de DMAE (DG) e protetores solares têm sido utilizados associados em formulações dermocosméticas antiidade. Apesar da ampla utilização dessas substâncias, métodos de quantificação para DG matéria-prima e em formulações cosméticas, especialmente quando associados, não estão descritos na literatura. Neste trabalho foram desenvolvidas e validadas metodologias por CLAE-FR e titulação em meio não-aquoso, com determinação do ponto final por potenciométrica (TP), para a rápida análise de DG matéria-prima e em emulsão tópica em associação com fotoprotetores. Ambos os métodos são simples, seletivos, lineares, exatos e precisos. O método TP foi escolhido para o estudo da estabilidade do DG na formulação desenvolvida. A formulação proposta apresentou um bom desempenho no que se refere a estabilidade, aspecto, pH, viscosidade aparente e SPF, com menos de 5% degradação do DG comparado as condições iniciais.


Assuntos
Deanol/administração & dosagem , Deanol/análise , Deanol/farmacologia , Protetores Solares/farmacologia , Tecnologia de Cosméticos , Cromatografia Líquida de Alta Pressão/estatística & dados numéricos
5.
Bioorg Med Chem ; 18(7): 2720-7, 2010 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-20226680

RESUMO

Effects of retro-inverso (RI) modifications of HTLV-1 protease inhibitors containing a hydroxyethylamine isoster backbone were clarified. Construction of the isoster backbone was achieved by a stereoselective aldol reaction. Four diastereomers with different configurations at the isoster hydroxyl site and the scissile site substituent were synthesized. Inhibitory activities of the new inhibitors suggest that partially modified RI inhibitors would interact with HTLV-1 protease in the same manner as the parent hydroxyethylamine inhibitor.


Assuntos
Ácido Aspártico Endopeptidases/antagonistas & inibidores , Deanol/análogos & derivados , Deanol/síntese química , Deanol/farmacologia , Inibidores de Proteases/síntese química , Inibidores de Proteases/farmacologia , Ácido Aspártico Endopeptidases/genética , Relação Dose-Resposta a Droga , Vírus Linfotrópico T Tipo 1 Humano/efeitos dos fármacos , Vírus Linfotrópico T Tipo 1 Humano/genética , Indicadores e Reagentes , Mutação , Relação Estrutura-Atividade
6.
Psychopharmacology (Berl) ; 207(2): 201-12, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19756528

RESUMO

RATIONALE: Dimethylaminoethanol pyroglutamate (DMAE p-Glu) is a compound resulting from the reaction between dimethylaminoethanol (an indirect precursor of acetylcholine) and pyroglutamic acid (a cyclic derivative of glutamic acid having procholinergic properties and promnesic effects in both animals and man). OBJECTIVES: The present study undertook preclinical and clinical evaluations to test a potential therapeutic utility for DMAE p-Glu in cognitive impairments related to central cholinergic deficit. MATERIALS AND METHODS: In preclinical study, DMAE p-Glu was studied in rats by intracerebral microdialysis in conscious freely moving animals, on performance of rats in the Morris water maze test of spatial memory, and on the deficit in passive avoidance behavior induced by scopolamine. The clinical study examined the effect of DMAE p-Glu on cognitive deficits induced by an intravenous injection of scopolamine in healthy young male subjects. RESULTS: In rat experiments, DMAE p-Glu increased the extracellular levels of choline and acetylcholine in the medial prefrontal cortex, as assessed by intracerebral microdialysis, improved performance in a test of spatial memory, and reduced scopolamine-induced memory deficit in passive avoidance behavior. Clinical study results show that scopolamine induced a memory deficit and that DMAE p-Glu produced a significant positive effect on scores in the Buschke test, as well as a slight but significant difference on choice reaction time. CONCLUSION: These results indicate that DMAE p-Glu reduces the deleterious effect of scopolamine on long-term memory in healthy volunteers and suggest that DMAE p-Glu might be effective in reducing memory deficits in patients with cognitive impairment.


Assuntos
Transtornos Cognitivos/tratamento farmacológico , Deanol/análogos & derivados , Glutamatos/farmacologia , Transtornos da Memória/tratamento farmacológico , Adulto , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Transtornos Cognitivos/induzido quimicamente , Estudos Cross-Over , Deanol/farmacologia , Método Duplo-Cego , Humanos , Masculino , Transtornos da Memória/induzido quimicamente , Microdiálise/métodos , Antagonistas Muscarínicos/toxicidade , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Escopolamina/toxicidade , Adulto Jovem
7.
Aesthetic Plast Surg ; 31(6): 711-8, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17940822

RESUMO

BACKGROUND: In clinical practice, dimethylaminoethanol (DMAE) has been used in the fight against wrinkles and flaccidity in the cervicofacial region. The firming action of DMAE is explained by the fact that its molecule, considered to be a precursor of acetylcholine, alters muscle contraction. However, no experimental studies have confirmed this theory. Because the actual mechanism of DMAE action was not defined and there were no references in the literature regarding its direct action on fibroblasts, this study was performed to evaluate the direct action of DMAE on cultured human fibroblasts. METHODS: Human fibroblasts obtained from discarded fragments of total skin from patients undergoing plastic or reconstructive surgical procedures performed within the Plastic Surgery Division at the Federal University of São Paulo were used for this study. The explant technique was used. The culture medium was supplemented with different concentrations of DMAE on the fourth cell passage, and the cell proliferation rate, cytosolic calcium levels, and cell cycle were evaluated. Statistical analysis was performed using analysis of variance (ANOVA) followed by a Newman-Keuls test for multiple comparisons. RESULTS: A decrease in fibroblast proliferation was associated with an increase in DMAE concentration. A longer treatment time with trypsin was required for the groups treated with DMAE in a dose-dependent manner. In the presence of DMAE, cytosolic calcium increased in a dose-dependent manner. Apoptosis also increased in groups treated with DMAE. CONCLUSION: Dimethylaminoethanol reduced the proliferation of fibroblasts, increased cytosolic calcium, and changed the cell cycle, causing an increase in apoptosis in cultured human fibroblasts.


Assuntos
Deanol/farmacologia , Fibroblastos/efeitos dos fármacos , Envelhecimento da Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Brasil , Comunicação Celular/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Pele/efeitos dos fármacos
8.
Phytomedicine ; 14(11): 711-5, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17923398

RESUMO

Tricutan is a combination product of herbal extracts traditionally used for treatment of skin conditions, together with dimethylaminoethanol. The effectiveness of Tricutan in improving skin firmness and elasticity in photoaged facial skin was examined in a randomised, placebo-controlled, double-blind, split-face study in 28 women, 34-67 years old. Treatment with Tricutan and placebo was given for 4 weeks. Skin firmness and elasticity was evaluated using the speed of propagation of ultrasound shear waves in the skin as end point (Reviscometer RVM 600). The study was completed by 25 women. The Tricutan treatment resulted in a significantly reduced propagation speed indicating increased firmness. There was no immediate effect by Tricutan application on propagation speed. At self evaluation the women evaluated the treatment effect of Tricutan to be significantly better than the treatment effect of placebo. The clinical evaluation also showed Tricutan to give a significantly better treatment result than placebo. Tolerance to Tricutan was generally good. However, three women did not complete the study because of mild irritative contact dermatitis. The results show that Tricutan can increase skin firmness both objectively and subjectively. Further studies are warranted, especially to investigate if Tricutan can delay the need for surgical face-lift procedures.


Assuntos
Deanol/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Ceratolíticos/farmacologia , Fitoterapia , Extratos Vegetais/farmacologia , Plantas Medicinais , Pele/efeitos dos fármacos , Administração Cutânea , Adulto , Idoso , Deanol/administração & dosagem , Deanol/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Face , Feminino , Humanos , Ceratolíticos/administração & dosagem , Ceratolíticos/uso terapêutico , Pessoa de Meia-Idade , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Envelhecimento da Pele/patologia , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Resultado do Tratamento
9.
Br J Dermatol ; 156(3): 433-9, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17300230

RESUMO

BACKGROUND: The 'cosmeceutical' agent 2-dimethylaminoethanol (DMAE) is a tertiary amine found in high concentration in numerous topical antiwrinkle preparations. OBJECTIVES: We hypothesized that a 337 mmol L(-1) (3%) DMAE reservoir applied to the skin could reproduce the cytopathology induced by other amines by maintaining a millimolar drug concentration within a certain depth of the skin layers, and that vacuolar cell expansion could account for the very rapid effect on the apparent skin fullness. METHODS: Morphological and functional assays were applied to cultured rabbit dermal fibroblasts treated with tertiary amines in vitro. A morphological verification of the vacuolization caused by topical DMAE was also attempted in vivo using the inner skin of the rabbit ear and in vitro using primary cultures of human cutaneous epithelial cells. RESULTS: Fibroblasts responded to DMAE (2.5-10 mmol L(-1)) by massive vacuolization (0.5-4 h; phase contrast observations). Triethanolamine, another chemical frequently used topically, was also active in this respect (10 mmol L(-1)). The vacuolar adenosine triphosphatase inhibitor bafilomycin A1 prevented DMAE- or triethanolamine-induced vacuolization; adding bafilomycin A1 or cell washout slowly reversed the established vacuolization induced by DMAE. Further effects of DMAE in cultured fibroblasts included a moderate cytotoxicity (10 mmol L(-1)) that was abated by bafilomycin A1 cotreatment, a concentration-dependent mitotic arrest (2.5 mmol L(-1)) and transient and mild effects on cell ploidy. The epidermis of the rabbit external ear was significantly thickened and exhibited clear perinuclear swelling indicative of vacuolization in response to 3% DMAE (1 h; paraffin tissue sections). Cultured human cutaneous epithelial cells responded to DMAE by vacuolization (inhibited by bafilomycin A1 cotreatment). CONCLUSIONS: The vacuolar cytopathology induced by concentrated organic amines may be the cellular basis of the antiwrinkle effect of DMAE.


Assuntos
Deanol/farmacologia , Fibroblastos/efeitos dos fármacos , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Vacúolos/efeitos dos fármacos , Animais , Morte Celular/efeitos dos fármacos , Células Cultivadas , Cosméticos/farmacologia , Relação Dose-Resposta a Droga , Células Epidérmicas , Epiderme/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Fibroblastos/ultraestrutura , Masculino , Microscopia de Contraste de Fase , Coelhos , Pele/citologia
10.
Vestn Oftalmol ; 122(6): 42-5, 2006.
Artigo em Russo | MEDLINE | ID: mdl-17217203
11.
Syst Appl Microbiol ; 28(3): 230-41, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15900970

RESUMO

The quaternary ammonium alcohols (QAAs) 2,3-dihydroxypropyl-trimethyl-ammonium (TM), dimethyl-diethanol-ammonium (DM) and methyl-triethanol-ammonium (MM) are hydrolysis products of their parent esterquat surfactants, which are widely used as softeners in fabric care. We isolated several bacteria growing with QAAs as the sole source of carbon and nitrogen. The strains were compared with a previously isolated TM-degrading bacterium, which was identified as a representative of the species Pseudomonas putida (Syst. Appl. Microbiol. 24 (2001) 252). Two bacteria were isolated with DM, referred to as strains DM 1 and DM 2, respectively. Based on 16S-rDNA analysis, they provided 97% (DM 1) and 98% (DM 2) identities to the closest related strain Zoogloea ramigera Itzigsohn 1868AL. Both strains were long, slim, motile rods but only DM 1 showed the floc forming activity, which is typical for representatives of the genus Zoogloea. Using MM we isolated a Gram-negative, non-motile rod referred to as strain MM 1. The 16S-rDNA sequence of the isolated bacterium revealed 94% identities (best match) to Rhodobacter sphaeroides only. The strains MM 1 and DM 1 exclusively grew with the QAA which was used for their isolation. DM 2 was also utilizing TM as sole source of carbon and nitrogen. However, all of the isolated bacteria were growing with the natural and structurally related compound choline.


Assuntos
Deanol/análogos & derivados , Compostos de Amônio Quaternário/metabolismo , Rhodobacter sphaeroides/isolamento & purificação , Rhodobacter sphaeroides/metabolismo , Tensoativos/metabolismo , Zoogloea/isolamento & purificação , Zoogloea/metabolismo , Técnicas de Tipagem Bacteriana , Biodegradação Ambiental , Carbono/metabolismo , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Deanol/metabolismo , Deanol/farmacologia , Genes de RNAr , Dados de Sequência Molecular , Nitrogênio/metabolismo , Propanóis/metabolismo , Propanóis/farmacologia , Compostos de Amônio Quaternário/farmacologia , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Rhodobacter sphaeroides/classificação , Rhodobacter sphaeroides/ultraestrutura , Análise de Sequência de DNA , Tensoativos/farmacologia , Zoogloea/classificação , Zoogloea/ultraestrutura
12.
Am J Clin Dermatol ; 6(1): 39-47, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15675889

RESUMO

Skincare formulations for the improvement of aging skin are increasingly important consumer products. Here, we review available data on one such agent - 2-dimethylaminoethanol (DMAE) or deanol - that has recently been evaluated in a placebo-controlled trial. DMAE is an analog of the B vitamin choline and is a precursor of acetylcholine. Although the role of acetylcholine as a neurotransmitter is well known, growing evidence points to acetylcholine as a ubiquitous cytokine-like molecule that regulates basic cellular processes such as proliferation, differentiation, locomotion, and secretion in a paracrine and autocrine fashion. Indeed, this modulatory role may contribute to the cutaneous activity of DMAE. In a randomized clinical study, 3% DMAE facial gel applied daily for 16 weeks has been shown to be safe and efficacious (p < 0.05) in the mitigation of forehead lines and periorbital fine wrinkles, and in improving lip shape and fullness and the overall appearance of aging skin. These effects did not regress during a 2-week cessation of application. Beneficial trends (p > 0.05 but

Assuntos
Deanol/farmacologia , Fármacos Dermatológicos/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Cosméticos/farmacologia , Humanos , Pele/efeitos dos fármacos
13.
J Biomed Mater Res A ; 66(1): 155-61, 2003 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-12833442

RESUMO

The increasing use of acrylate-based resins in dentistry has raised questions about the biocompatibility of these substances with oral tissues. The focus of the present investigation was to assess the responsiveness of blood vessels to the resin polymerization accelerating agent dimethylaminoethyl methacrylate (DMAEMA) and its degradation products dimethylethanolamine (DME) and methacrylic acid (MAA), using the rat aortic ring preparation as a tissue model. DMAEMA induced concentration-dependent relaxation of norepinephrine (NE)-contracted aortic rings with and without endothelium. N-nitro-L-arginine methyl ester (L-NAME) selectively inhibited the endothelium-dependent relaxation induced by DMAEMA, suggesting the release of nitric oxide from the endothelium by DMAEMA. Both indomethacin and glybenclamide attenuated the vasorelaxation elicited by DMAEMA in the presence as well as in the absence of endothelium, providing evidence for the role of vasorelaxant prostanoid(s) and K(ATP) channel activation in the responses observed. On the other hand, while MAA was without any apparent effect on the rat aorta, DMAEMA at high and DME at relatively low concentrations caused contraction of the tissues with and without endothelium in the absence of NE. The DME-induced contraction was inhibited by indomethacin, suggesting the involvement of contractile arachidonic acid metabolite(s) in the action of DME. This observation was supported by the findings of increased thromboxane A(2) (TXA(2)) production in aortic rings incubated with DME. Taken together, the data suggest that both DMAEMA and its degradation product, DME, are vasoactive, inducing vasorelaxation and contraction by various mechanisms that may involve the release of nitric oxide from the endothelium, the activation of smooth muscle K(ATP) channels, and the generation of vasorelaxant prostanoid(s) and TXA(2). These effects may play a role in tissue homeostasis and certain adverse conditions associated with the use of dental resin materials containing DMAEMA and/or DME.


Assuntos
Resinas Acrílicas/farmacologia , Aorta Torácica/efeitos dos fármacos , Materiais Biocompatíveis/farmacologia , Deanol/farmacologia , Materiais Dentários/farmacologia , Metacrilatos/farmacologia , Resinas Sintéticas/farmacologia , Acetilcolina/farmacologia , Animais , Aorta Torácica/metabolismo , Aorta Torácica/fisiologia , Inibidores de Ciclo-Oxigenase/farmacologia , Endotélio Vascular/efeitos dos fármacos , Glibureto/farmacologia , Indometacina/farmacologia , Contração Isométrica/efeitos dos fármacos , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Norepinefrina/farmacologia , Prostaglandinas/biossíntese , Ratos , Ratos Endogâmicos WKY , Tromboxano A2/biossíntese , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos
14.
Skin Res Technol ; 8(3): 164-7, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12236885

RESUMO

BACKGROUND/AIMS: Beyond subjective assessments, the effect of skin tensors is difficult to assess. The present 2-phase randomized double-blind split face study was designed to compare the effect of a gel containing 3% 2-dimethylaminoethanol (deanol, DMAE) with the same formulation without DMAE. METHODS: In a first pilot study, sensorial assessments and measures of the skin distension under suction were performed in eight volunteers. In a second study conducted in 30 volunteers, shear wave propagation was measured. RESULTS: Large interindividual variations precluded any significant finding in the first study. The DMAE formulation showed, however, a significant effect characterized by increased shear wave velocity in the direction where the mechanical anisotropy of skin showed looseness. CONCLUSION: The DMAE formulation under investigation increased skin firmness.


Assuntos
Deanol/farmacologia , Fármacos Dermatológicos/farmacologia , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Adulto , Anisotropia , Dermatologia/métodos , Método Duplo-Cego , Feminino , Géis , Humanos , Pessoa de Meia-Idade , Veículos Farmacêuticos/farmacologia , Projetos Piloto , Pele/efeitos dos fármacos , Sucção , Resistência à Tração
15.
Ann N Y Acad Sci ; 959: 308-20; discussion 463-5, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11976205

RESUMO

As was shown in a recent review by this author (Ann. N.Y. Acad. Sci., 928: 187-199, 2001), oxyradicals cannot be considered only as harmful by-products of the oxidative metabolism, but living cells and organisms implicitly require their production. This idea is supported by numerous facts and arguments, the most important of which is that the complete inhibition of the oxyradical production by KCN (or by any block of respiration) kills the living organisms long before the energy reserves would be exhausted. This new theoretical approach not only helps our understanding of the normal functions of the living organisms, such as the basic memory mechanisms in the brain cells, but also helps in identifying the site-specific, radical-induced damaging mechanisms that represent the undesirable side effects of oxygen free radicals. First of all, these effects make the cell plasma membrane vulnerable and cause a series of intracellular functional disorders, as described by the membrane hypothesis of aging (MHA). The logical way for any antiaging intervention therefore should be to increase the available number of loosely bound electrons inside the plasma membrane that are easily accessible for OH(*) free radical scavenging. The present review summarizes the available knowledge regarding the theory of the use of membrane-related antiaging pharmaca, like centrophenoxine (CPH), tested in both animal experiments and human clinical trials. A modified, developed version of CPH coded as BCE-001 is also reported.


Assuntos
Envelhecimento/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Meclofenoxate/análogos & derivados , Ácido 2,4-Diclorofenoxiacético/análogos & derivados , Ácido 2,4-Diclorofenoxiacético/química , Ácido 2,4-Diclorofenoxiacético/farmacologia , Envelhecimento/fisiologia , Animais , Encéfalo/citologia , Encéfalo/fisiologia , Membrana Celular/química , Membrana Celular/metabolismo , Deanol/química , Deanol/farmacologia , Ésteres/farmacologia , Sequestradores de Radicais Livres/metabolismo , Humanos , Expectativa de Vida , Meclofenoxate/farmacologia , Modelos Biológicos , Psicotrópicos/farmacologia , Sinaptossomos/química , Sinaptossomos/metabolismo
16.
FASEB J ; 16(6): 619-21, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11919173

RESUMO

A role for choline during early stages of mammalian embryogenesis has not been established, although recent studies show that inhibitors of choline uptake and metabolism, 2-dimethylaminoethanol (DMAE), and 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3), produce neural tube defects in mouse embryos grown in vitro. To determine potential mechanisms responsible for these abnormalities, choline metabolism in the presence or absence of these inhibitors was evaluated in cultured, neurulating mouse embryos by using chromatographic techniques. Results showed that 90%-95% of 14C-choline was incorporated into phosphocholine and phosphatidylcholine (PtdCho), which was metabolized to sphingomyelin. Choline was oxidized to betaine, and betaine homocysteine methyltransferase was expressed. Acetylcholine was synthesized in yolk sacs, but 70 kDa choline acetyltransferase was undetectable by immunoblot. DMAE reduced embryonic choline uptake and inhibited phosphocholine, PtdCho, phosphatidylethanolamine (PtdEtn), and sphingomyelin synthesis. ET-18-OCH3 also inhibited PtdCho synthesis. In embryos and yolk sacs incubated with 3H-ethanolamine, 95% of recovered label was PtdEtn, but PtdEtn was not converted to PtdCho, which suggested that phosphatidylethanolamine methyltransferase (PeMT) activity was absent. In ET-18-OCH3 treated yolk sacs, PtdEtn was increased, but PtdCho was still not generated through PeMT. Results suggest that endogenous PtdCho synthesis is important during neurulation and that perturbed choline metabolism contributes to neural tube defects produced by DMAE and ET-18-OCH3.


Assuntos
Sistema Nervoso Central/embriologia , Colina/metabolismo , Acetilcolina/biossíntese , Animais , Betaína/metabolismo , Células Cultivadas , Sistema Nervoso Central/metabolismo , Ceramidas/metabolismo , Deanol/farmacologia , Diglicerídeos/metabolismo , Embrião de Mamíferos/efeitos dos fármacos , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário e Fetal , Gástrula/metabolismo , Camundongos , Modelos Neurológicos , Fosfatidilcolinas/biossíntese , Éteres Fosfolipídicos/farmacologia , Fosforilcolina/metabolismo , Esfingomielinas/biossíntese
17.
Dig Dis Sci ; 46(6): 1290-8, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11414307

RESUMO

Biliary phospholipid secretion is mediated by a multidrug resistance gene product, and its molecular subselection occurs at the site of secretion to modulates bile metastability. The aim of this study was to determine the effect of modifying hepatic phospholipid synthesis on canalicular phospholipid transporter expression and membrane fluidity. Bile-duct cannulation was performed in male Sprague-Dawley rats pretreated with or without intravenous infusion of dimethylethanolamine, an intermediate phospholipid metabolite along the pathway of phosphatidylcholine synthesis of phosphatidylethanolamine N-methylation (0.01 mg/min/100 g body wt) for 15 hr, followed by sodium taurocholate infusion (50 nmol/min/100 g body wt) with or without sulfobromophthalein (50 nmol/min/100 g body wt). Dimethylethanolamine enhanced biliary phospholipid secretion in association with a decrease in biliary phospholipid hydrophobicity. Dimethylethanolamine also increased canalicular membrane fluidity defined by 1,6-diphenyl-1,3,5-hexatriene fluorescence depolarization, whereas the expression of multidrug resistance gene product and multidrug resistance associated protein was unchanged. In contrast, a disproportionate reduction of biliary phospholipid secretion caused by sulfobromophthalein (uncoupling) was enhanced by under the treatment with dimethylethanolamine. In conclusion, the increase in biliary phospholipid secretion and canalicular membrane fluidity without a drastic change of its canalicular transporter by dimethylethanolamine suggests that such a canalicular membrane fluidity facilitates the transporter activity and/or phospholipid molecular movement from the canalicular outer membrane into the bile. A more drastic reduction in phospholipid secretion under sulfobromophthalein-caused uncoupling indicates the possibility of a preferential distribution of relatively hydrophilic phosphatidylcholine molecules to bile salt micelles since sulfobromophthalein is known to reduce the micellar capacity to extract membrane lipids for biliary secretion.


Assuntos
Canalículos Biliares/fisiologia , Ductos Biliares/metabolismo , Fígado/metabolismo , Fluidez de Membrana/fisiologia , Fosfolipídeos/biossíntese , Fosfolipídeos/metabolismo , Animais , Bile/metabolismo , Canalículos Biliares/efeitos dos fármacos , Ductos Biliares/efeitos dos fármacos , Deanol/farmacologia , Masculino , Fluidez de Membrana/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
18.
J Neurochem ; 76(3): 910-8, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11158263

RESUMO

The present work examines the effect of membrane lipid composition on activation of extracellular signal-regulated protein kinases (ERK) and cell death following oxidative stress. When subjected to 50 microM docosahexaenoic acid (DHA, 22 : 6 n-3), cellular phospholipids of OLN 93 cells, a clonal line of oligodendroglia origin low in DHA, were enriched with this polyunsaturated fatty acid. In the presence of 1 mM N,N-dimethylethanolamine (dEa) a new phospholipid species analog was formed in lieu of phosphatidylcholine. Exposure of DHA-enriched cells to 0.5 mM H2O2, caused sustained activation of ERK up to 24 h. At this time massive apoptotic cell death was demonstrated by ladder and TUNEL techniques. H2O2-induced stress applied to dEa or DHA/dEa co-supplemented cells showed only a transient ERK activation and no cell death after 24 h. Moreover, while ERK was rapidly translocated into the nucleus in DHA-enriched cells, dEa supplements completely blocked ERK nuclear translocation. This study suggests that H2O2-induced apoptotic cell death is associated with prolonged ERK activation and nuclear translocation in DHA-enriched OLN 93 cells, while both phenomena are prevented by dEa supplements. Thus, the membrane lipid composition ultimately modulates ERK activation and translocation and therefore can promote or prevent apoptotic cell death.


Assuntos
Apoptose/fisiologia , Peróxido de Hidrogênio/farmacologia , Lipídeos/fisiologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/fisiologia , Oxidantes/farmacologia , Transporte Biológico/fisiologia , Butadienos/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular , Núcleo Celular/enzimologia , Deanol/farmacologia , Ácidos Docosa-Hexaenoicos/farmacologia , Resistência a Medicamentos , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Inibidores Enzimáticos/farmacologia , Nitrilas/farmacologia , Oligodendroglia/citologia , Oligodendroglia/metabolismo , Estresse Oxidativo , Fatores de Tempo
19.
Am J Physiol ; 272(1 Pt 2): F94-9, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9039054

RESUMO

The trimethylamine glycine-betaine is accumulated to high concentrations in medullary cells of mammalian kidneys, whereas betaine synthesis from choline is predominant in the renal cortex. We investigated the contribution of renal betaine synthesis to medullary betaine accumulation. De novo synthesis of betaine in situ was accomplished by injecting [14C]choline into the renal artery of male Sprague-Dawley rats. [14C]betaine was measured in the renal cortex and medulla, as well as in serum and urine samples. Betaine concentration in the cortex decreased from 3.5 +/- 1.3 at 5 min to 0.4 +/- 0.2 nmol/mg protein at 60 min, but it increased from 1.4 +/- 0.1 to 2.5 +/- 0.6 nmol/mg protein in the medulla. Serum and total urine [14C]betaine increased from 2.7 +/- 1.3 and 0.9 +/- 0.1 nmol/ml at 5 min to 5.3 +/- 0.3 and 2.1 +/- 0.4 nmol/ml at 60 min, respectively. Concentrations of newly synthesized betaine were not decreased by the ligation of the hepatic artery and portal vein, suggesting that most [14C]betaine was synthesized in the kidney. Coinjection with 5 mM dimethylamino-ethanol, a choline oxidase inhibitor, and 100 mM cold betaine reduced medullary betaine accumulation by 80 and 76%, respectively. Water deprivation for 60 h increased both cortical and medullary [14C]betaine, whereas furosemide diuresis decreased the medullary [14C]betaine concentration. We concluded that betaine synthesized in the kidney can be accumulated in the medulla and that the medullary concentrations of newly synthesized betaine are closely related to the hydration state of the animal.


Assuntos
Betaína/metabolismo , Rim/metabolismo , Animais , Betaína/urina , Deanol/farmacologia , Diurese , Diuréticos/farmacologia , Furosemida/farmacologia , Artéria Hepática , Medula Renal/metabolismo , Ligadura , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Distribuição Tecidual , Privação de Água/fisiologia , Equilíbrio Hidroeletrolítico
20.
Fiziol Zh (1994) ; 43(1-2): 19-22, 1997.
Artigo em Ucraniano | MEDLINE | ID: mdl-9221114

RESUMO

The effects of inhaling action of dimethylethanolamine (twenty-four-hour for four months (on summarizing liminal index, SLI) and efficiency of white rats in dependence on various concentrations of amino alcohol were studied in chronic experiments. The obtained results allowed to conclude, that high (2.76 mg/m3) concentration of dimethylethanolamine influenced on functional state of central nervous system. SLI changes pointed to disturbance of dynamic equilibrium between processes of inhibition and excitation with prevalence of latter. In the same time the sufficient grounds for the attribution of dimethylethanolamine to myorelaxants were absent, since in our experiments we used only very high concentrations of this agent.


Assuntos
Antidepressivos/farmacologia , Sistema Nervoso Central/fisiologia , Deanol/farmacologia , Administração por Inalação , Animais , Antidepressivos/administração & dosagem , Deanol/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Ratos , Fatores de Tempo
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