Advances in basic research on choline and central nervous system development and related disorders / 中华预防医学杂志

Choline is an essential nutrient that plays an integral role in all stages of the life cycle, with increasing interest in the relationship between choline and neurodevelopment. Choline is a major component in the synthesis of phospholipids, phosphatidylcholine and sphingolipids, and is an essential nutrient for methyl metabolism, acetylcholine synthesis and cell signaling. Choline plays an important role in neurogenesis and neural migration during fetal development, potentially influencing the development and prognosis of neurological disorders, but its mechanism of action is not yet clear. This article reviews the source and metabolism of choline, the effects and mechanism of choline on neurodevelopment and central nervous system related disorders.

Leishmania amazonensis exhibits phosphatidylserine-dependent procoagulant activity, a process that is counteracted by sandfly saliva

Leishmania parasites expose phosphatidylserine (PS) on their surface, a process that has been associated with regulation of host's immune responses. In this study we demonstrate that PS exposure by metacyclic promastigotes of Leishmania amazonensis favours blood coagulation. L. amazonensis accelerates in vitro coagulation of human plasma. In addition, L. amazonensis supports the assembly of the prothrombinase complex, thus promoting thrombin formation. This process was reversed by annexin V which blocks PS binding sites. During blood meal, Lutzomyia longipalpis sandfly inject saliva in the bite site, which has a series of pharmacologically active compounds that inhibit blood coagulation. Since saliva and parasites are co-injected in the host during natural transmission, we evaluated the anticoagulant properties of sandfly saliva in counteracting the procoagulant activity of L. amazonensis . Lu. longipalpis saliva reverses plasma clotting promoted by promastigotes. It also inhibits thrombin formation by the prothrombinase complex assembled either in phosphatidylcholine (PC)/PS vesicles or in L. amazonensis . Sandfly saliva inhibits factor X activation by the intrinsic tenase complex assembled on PC/PS vesicles and blocks factor Xa catalytic activity. Altogether our results show that metacyclic promastigotes of L. amazonensis are procoagulant due to PS exposure. Notably, this effect is efficiently counteracted by sandfly saliva.

Pulmonary surfactants and their role in pathophysiology of lung disorders.

Surfactant is an agent that decreases the surface tension between two media. The surface tension between gaseous-aqueous interphase in the lungs is decreased by the presence of a thin layer of fluid known as pulmonary surfactant. The pulmonary surfactant is produced by the alveolar type-II (AT-II) cells of the lungs. It is essential for efficient exchange of gases and for maintaining the structural integrity of alveoli. Surfactant is a secretory product, composed of lipids and proteins. Phosphatidylcholine and phosphatidylglycerol are the major lipid constituents and SP-A, SP-B, SP-C, SP-D are four types of surfactant associated proteins. The lipid and protein components are synthesized separately and are packaged into the lamellar bodies in the AT-II cells. Lamellar bodies are the main organelle for the synthesis and metabolism of surfactants. The synthesis, secretion and recycling of the surfactant lipids and proteins is regulated by complex genetic and metabolic mechanisms. The lipid-protein interaction is very important for the structural organization of surfactant monolayer and its functioning. Alterations in surfactant homeostasis or biophysical properties can result in surfactant insufficiency which may be responsible for diseases like respiratory distress syndrome, lung proteinosis, interstitial lung diseases and chronic lung diseases. The biochemical, physiological, developmental and clinical aspects of pulmonary surfactant are presented in this article to understand the pathophysiological mechanisms of these diseases.

Modulation of lecithin activity by vitamin-B complex to treat long term consumption of ethanol induced oxidative stress in liver.

Alcoholic liver disease (ALD) develops as a consequence of priming and sensitizing mechanisms rendered by cross-interactions of primary mechanistic factors and secondary risk factors. Chronic alcohol abuse and its progression to ALD are associated with abnormal metabolism and low tissue or plasma levels, or both, of many micronutrients. Glutathione depletion is considered the most important sensitizing mechanism. In the present study efficacy of lecithin with vitamin-B complex to treat ethanol induced oxidative stress was compared with the effect of lecithin alone, tocopheryl acetate (vitamin E), as well as capacity of hepatic regeneration during abstention. Ethanol (1.6g / kg body weight/ day for 4 weeks) affects body weight in 16-18 week old male albino rats of Wistar strain weighing 200-220 g. Thiobarbituric acid reactive substance level, nitrite content, protein carbonyl group level, redox ratio (oxidized to reduced glutathione ratio), superoxide dismutase activity, and glutathione s-transferase activity significantly increased on ethanol exposure. Whereas reduced glutathione content, and activities of catalase, glutathione reductase and glutathione peroxidase significantly reduced due to ethanol exposure. These changes were reversed by different treatment. The results suggest that tocopheryl acetate (vitamin E) could partially reverse these changes and act as a potential therapeutic agent. However, lecithin with vitamin-B complex treatment is a promising therapeutic approach. Furthermore, preventive measures were more effective than curative treatment. Prevention of oxidative and nitrosative stress along with correction of nutritional deficiency is one of the proposed mechanisms for the therapeutic approach.

Espectroscopia de prótons (1H) por ressonância magnética, neuroquímica cerebral e diagnóstico de doenças neurológicas / Proton (1H) magnetic resonance spectroscopy, brain neurochemistry, and diagnosis of neurological diseases

A técnica de espectroscopia de prótons (1H) por ressonância magnética do cérebro permite identificar, in vivo e de modo näo-invasivo, neurometabolitos pertencentes a diversas vias do metabolismo intermediário. A análise desses achados é o objetivo da presente revisäo. As bases do método e os principais metabolitos que constituem o espectro säo considerados, assim como as vias neuroquímicas relacionadas com importantes funçöes metabólicas e os neurometabolitos representativos das mesmas, possíveis de serem observados no espectro em condiçöes normais e patológicas. O conhecimento dessas relaçöes aponta para aspectos neuroquímicos da amostra de tecido nervoso examinada e permite hipóteses fisiológicas e fisiopatológicas relativas às variaçöes dos principais metabolitos. Säo descritas variaçöes regionais e em relaçäo ao envelhecimento normal, importantes na seleçäo e comparaçäo de amostras adequadamente pareadas, sobretudo em situaçäo de pesquisa. A aplicaçäo da técnica no diagnóstico em neurologia também é considerada, com ênfase em doenças degenerativas. Conclui-se ser uma técnica de grande utilidade clínica e que contribui de modo significativo no aprofundamento disgnóstico, assim como na monitorizaçäo terapêutica e no acompanhamento evolutivo de doenças neurológicas

Zinc in the prevention of Fe2+-initiated lipid and protein oxidation

In the present study we characterized the capacity of zinc to protect lipids and proteins from Fe2+-initiated oxidative damage. The effects of zinc on lipid oxidation were investigated in liposomes composed of brain phosphatidylcholine (PC) and phosphatidylserine (PS) at a molar relationship of 60:40 (PC:PS, 60:40). Lipid oxidation was evaluated as the oxidation of cis-parinaric acid or as the formation of 2-thiobarbituric acid-reactive substances (TBARS). Zinc protected liposomes from Fe2+ (2.5-50 microM)-supported lipid oxidation. However, zinc (50 microM) did not prevent the oxidative inactivation of glutamine synthetase and glucose 6-phosphate dehydrogenase when rat brain supernatants were oxidized in the presence of 5 microM Fe2+ and 0.5 mM H2O2. We also studied the interactions of zinc with epicatechin in the prevention of lipid oxidation in liposomes. The simultaneous addition of 0.5 microM epicatechin (EC) and 50 microM zinc increased the protection of liposomes from oxidation compared to that observed in the presence of zinc or EC separately. Zinc (50 microM) also protected liposomes from the stimulatory effect of aluminum on Fe2+-initiated lipid oxidation. Zinc could play an important role as an antioxidant in biological systems, replacing iron and other metals with pro-oxidant activity from binding sites and interacting with other components of the oxidant defense system.

Estudio histoquímico ultraestructural con lecitinas del cáncer gástrico y mucosa adyacente / Lectins in gastric cancer. A histochemical and ultraestructural study

Hemos realizado un estudio ultraestructural con 5 tipows de lecitinas (UEA-1, PNA, WGA, SBA and DBA) en 25 piezas de gastrecromía con adenocarcinoma, con el objeto de establecer diferencias entre la composición del moco secretado por la mucosa aparentemente normal y la neoplásica. Todas las muestras fueron incluidas en resina Sprurr y LR White, con diferentes condiciones de fijación y deshidratación; además, las lecitinas fueron incubadas siguiendo dos métodos diferentes: directo e indirecto. Los mejores resultados fueron obtenidoscon el método indirecto en el tejido incluido en LR White. Nuestros resultados muestran una gran hetereogenicidad en la composición azucarada, especialmente en la secreción de la mucoso neoplásica. La reacción con WGA fue negativa en el moco extracelular secretado en normalidad, mientras que resultó positiva en el secretado por las células neoplásicas. En marcaje con SBA sobre el aparato de Golgi sugiere que el inicio de la glicosilación sucede a nivel de la cara cis, aunque no podemos excluir que en ocaciones se realice en el retículo endoplásmatico rugoso. La intensidad en el marcaje con lecitinas aumentó con la diferenciación tumoral. La presencia de reacción con WGA en el moco extracelular en los carcinomas, así como la distribución azarosa de la reacción sobre el aparato de Golgi, podría estar relacionadas con glicosilaciones aberrantes y/o elongaciones anormales de la cadena de carbohidratos.

The molecular interaction between F-actin and lecithin in a phospholipid monolayer system

En el presente trabajo se estudia la interacción entre la actina polimérica (F) y la difosfatidilcolina empleando un sistema modelo de membrana biológica como es la monocapa de fosfolípido. Los cambios en la transición de fase (TF) que muestra la monocapa de lecitina al ser comprimida lateralmente nos sirven de parámetro indicativo de la interacción del lípido con la proteína. Hemos encontrado que la F-actina, en una concentración muy pequeña respecto a la lecitina (relación molar 1:2,000), reduce la presión superficial (pi, medida en el inicio de la TF) del lípido. Esta disminución muestra dos hechos: (a) que hay una interacción lípido-proteína específica, y (b) que la fluidez de la fase lípidica disminuye por la presencia de la F-actina. La adición de iones calcio a la subface acuosa de la monocapa del lípido puro, produce también una disminución de la pi T. Al adicionar a la monocapa mixta (lípido y proteína) el calcio. Este disminuye también la pi T del sistema aunque el efecto es simplemente aditivo. En vista de los resultados obtenidos, se avisora sobre la forma posible en que las moléculas de F-actina y fosfolípido interactúan y su significado para explicar algunos fenómenos de la superfície celular donde se ha reportado la presencia y participación de esta proteína