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.

The efficacy of saxagliptin in T2DM patients with non-alcoholic fatty liver disease: preliminary data

SUMMARY OBJECTIVE To investigate the clinical efficacy and the possible mechanisms of saxagliptin in the treatment of type 2 diabetes mellitus (T2DM) combined with non-alcoholic fatty liver disease (NAFLD). METHODS A total of 95 T2DM and NAFLD patients were randomly divided into group A (saxagliptin group), group B (glimepiride group), and group C (glimepiride combined with polyene phosphatidylcholine group). RESULTS After intervention treatment for 24 w, body mass index (BMI), waist-to-hip ratio (WHR), glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), interleukin-6 (IL-6), triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), and quantitative detection of liver steatosis of study subjects were observed, the action of liver steatosis in subjects of groups A and C were significantly different from those of group B; however, there were no differences between groups A and C. The FINS, HOMA-IR, and IL-6 of subjects in group A was lower than those in groups B and C; however, there were no significant differences between the latter two groups. CONCLUSION For T2DM combined with NAFLD patients, the saxagliptin treatment could not only effectively control blood glucose but also attenuate insulin resistance and inflammatory injury of the liver to improve fatty liver further.

RESUMO OBJETIVO Investigar a eficácia clínica e os possíveis mecanismos da saxagliptina no tratamento do diabetes mellitus tipo 2 (DM2) associado à doença hepática gordurosa não alcoólica (DHGNA). MÉTODOS Um total de 95 DM2 combinados com pacientes com DHGNA foram aleatoriamente divididos em grupo A (grupo saxagliptina), grupo B (grupo glimepirida) e grupo C (glimepirida combinado com grupo fosfatidilcolina polienizada). RESULTADOS Após a intervenção tratamento por 24 w, índice de massa corporal (IMC), relação cintura-quadril (RCQ), hemoglobina glicada (HbA1c), glicemia de jejum (FPG), insulina de jejum (Fins), avaliação do modelo homeostático de insulina resistência (Homa-IR), interleucina-6 (IL-6), triglicérides (TG), colesterol total (CT), alanina aminotransferase (ALT), aspartato aminotransferase (AST), γ-glutamiltransferase (γ-GT) e detecção de esteatose hepática dos sujeitos do estudo foram observados. Ação de esteatose hepática de indivíduos nos grupos A e C foram significativamente diferentes do grupo B; no entanto, não houve diferenças entre os grupos A e C. Os grupos Fins, Homa-IR e IL-6 dos participantes do grupo A foram menores que os dos grupos B e C; no entanto, não houve diferenças significativas entre os dois últimos grupos. CONCLUSÃO Para o DM2 combinado com pacientes com DHGNA, o tratamento com saxagliptina pode não apenas controlar efetivamente a glicemia, mas também atenuar a resistência à insulina e a lesão inflamatória do fígado para melhorar ainda mais o fígado gorduroso.

Egg phospholipids exert an inhibitory effect on intestinal cholesterol absorption in mice

BACKGROUND/OBJECTIVES: Consumption of cholesterol-rich foods, such as eggs, has a minimal effect on circulating cholesterol levels in healthy humans. To gain insight, we investigated whether phospholipids rich in eggs (EPL) interfere with intestinal cholesterol absorption in vivo. MATERIALS/METHODS: To investigate the acute effect of EPL on intestinal cholesterol absorption, male C57BL/6J mice were orally administered with 6, 11, or 19 mg of EPL for three days. We also tested the effect of chronic EPL consumption on cholesterol metabolism in the small intestine and the liver in mice with diet-induced hypercholesterolemia. Male C57BL/6J mice were fed a high fat/high cholesterol (HF/HC; 35% fat, 0.25% cholesterol, w/w) diet for 4 weeks to induce hypercholesterolemia, and subsequently the mice were either fed 0, 0.4 or 0.8% (w/w) of EPL for 6 weeks. RESULTS: Intestinal cholesterol absorption was significantly decreased by the highest dose of acute EPL administration compared to control. Chronic EPL supplementation did not significantly alter intestinal cholesterol absorption nor plasma levels of total cholesterol and low-density lipoprotein cholesterol. In the small intestine and the liver, EPL supplementation minimally altered the expression of genes which regulate cellular cholesterol levels. CONCLUSION: Although chronic EPL consumption was not able to counteract hypercholesterolemia in HF/HC-fed mice, acute EPL administration decreased intestinal cholesterol absorption. This study provides in vivo evidence that acute administration of PLs in eggs prevent cholesterol absorption in the intestine, suggesting a mechanism for a minimal effect of egg consumption on circulating cholesterol levels.

Lipidomic analysis of plasma lipids composition changes in septic mice

A lipidomic study on extensive plasma lipids in bacterial peritonitis (cecal ligation and puncture, CLP)-induced sepsis in mice was done at 24 h post-CLP. The effects of administration of lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), compounds known to have beneficial effects in CLP, on the sepsis-induced plasma lipid changes were also examined. Among the 147 plasma lipid species from 13 lipid subgroups (fatty acid [FA], LPA, LPC, lysophosphatidylethanolamine [LPE], phosphatidic acid [PA], phosphatidylcholine [PC], phosphatidylethanolamine [PE], phosphatidylinositol [PI], monoacylglyceride [MG], diacylglyceride [DG], triacylglyceride [TG], sphingomyelin [SM], and ceramide [Cer]) analyzed in this study, 40 and 70 species were increased, and decreased, respectively, in the CLP mice. Treatments with LPC and LPA affected 14 species from 7 subgroups, and 25 species from 9 subgroups, respectively. These results could contribute to finding the much needed reliable biomarkers of sepsis.

Uso de injeções lipolíticas com desoxicolato de sódio em depósitos de gordura: contexto histórico e atual / Lipolysis injections with sodium deoxycholate: historical and current context

Desde a primeira publicação a respeito, em 2001, a aplicação de injeções lipolíticas para gordura localizada tornou-se um procedimento amplamente utilizado na clínica. Consiste de múltiplas injeções subcutâneas de compostos lipolíticos, que podem ter diversos mecanismos de ação. O fármaco mais utilizado atualmente, o desoxicolato de sódio, foi descoberto por acaso, em uma associação com fosfatidilcolina em que sua única função era de veículo da fórmula. Conforme estudos foram sendo realizados, concluiu-se que a ação no tecido era devido ao desoxicolato, um sal biliar que emulsiona os lipídios da membrana celular, resultando em lise do adipócito e consequente necrose do tecido adiposo. Seus principais efeitos adversos, muito frequentemente relatados, incluem dor intensa, edema e formação de nódulos fibrosos nos pontos aplicados. Em decorrência de falhas na aplicação, alguns efeitos adversos mais graves podem ocorrer, como injúria do nervo facial e infecções persistentes. Apesar destes, a utilização de desoxicolato de sódio na camada subcutânea apresenta resultados muito positivos, como publicado em diversos ensaios clínicos, inclusive com relação à satisfação do paciente perante o desfecho final, sendo, portanto, uma boa escolha de técnica para contorno corporal e diminuição de depósitos de gordura localizados. (AU)

Since the first paper, in 2001, injection lipolysis for localized fat deposits became a widely used procedure in the clinics. It consists basically of multiple subcutaneous injections of lipolytic compounds, with many different mechanisms of action. The most used drug nowadays is sodium deoxycholate, initially thought to be only the solubilizing vehicle in the phosphatidilcholine formula. As studies were performed, it was concluded that the changes seen in the tissue was due to sodium deoxycholate, a biliary salt which emulsifies membrane lipids, resulting in adipocyte lysis and consequent adipose tissue necrosis. Its main adverse events include pain, oedema and fibrous nodules. Due to poor technique, more serious adverse events may happen, such as nerve injury or persistent infection by mycobacterium. In spite of these, the use of sodium deoxycholate presents great results, as published in many clinical trials, including patient's satisfaction at the end of the treatment, which is of much value in the aesthetics field. Therefore, mesotherapy using sodium deoxycholate is a good choice for body contouring and localized fat deposits. (AU)

Prurigo Pigmentosa after Injection Lypolysis with Phosphatidylcholine and Deoxycholate / 대한피부과학회지

No abstract available.

Artificial gait in complete spinal cord injured subjects: how to assess clinical performance / Marcha artificial em indivíduos com lesão medular completa: como avaliar desempenho clínico

Objective Adapt the 6 minutes walking test (6MWT) to artificial gait in complete spinal cord injured (SCI) patients aided by neuromuscular electrical stimulation. Method Nine male individuals with paraplegia (AIS A) participated in this study. Lesion levels varied between T4 and T12 and time post injured from 4 to 13 years. Patients performed 6MWT 1 and 6MWT 2. They used neuromuscular electrical stimulation, and were aided by a walker. The differences between two 6MWT were assessed by using a paired t test. Multiple r-squared was also calculated. Results The 6MWT 1 and 6MWT 2 were not statistically different for heart rate, distance, mean speed and blood pressure. Multiple r-squared (r2 = 0.96) explained 96% of the variation in the distance walked. Conclusion The use of 6MWT in artificial gait towards assessing exercise walking capacity is reproducible and easy to apply. It can be used to assess SCI artificial gait clinical performance. .

Objetivo Adaptar o teste de caminhada dos 6 minutos (TC6) para marcha artificial de pacientes com lesão medular completa associado a eletroestimulação neuromuscular. Método Nove participantes do sexo masculino com paraplegia (AIS A) participaram do estudo. O nível de lesão variou entre T4 e T12 , tempo de lesão variou entre 4 e 13 anos. Os pacientes realizaram dois TC6 (TC6-1 e TC6-2). Os participantes usaram eletroestimulação neuromuscular e foram auxiliados por andador. As diferenças entre os dois TC6 foram avaliadas pelo teste t pareado e calculado o r2. Resultados Não foi encontrada diferença estatística entre TC6-1 e TC6-2 para frequência cardíaca, distância, velocidade média e pressão arterial. O r2 = 0,96 explica 96% da variação na distância caminhada. Conclusão O uso do TC6 em marcha artificial para avaliação da capacidade de exercício de caminhada é reprodutível e fácil de aplicar. Esse teste pode ser utilizado para avaliar o desempenho clínico da marcha artificial de indivíduos com lesão medular. .

Hair Growth Promoting Potential of Phospholipids Purified from Porcine Lung Tissues

BP201, porcine lung tissue-derived phospholipids, consists of phosphatidylcholine as a major phospholipid species. BP201 promoted hair growth after application onto the shaved backs of BALB/c and C3H mice. Its effect was enhanced when applied together with minoxidil (MNX) in C3H mice. When the tissue specimens prepared from the shaved skins of BP201-treated and control mice were microscopically examined, the total numbers of hair follicles in both anagen and telogen phases of BP201-treated mice were significantly higher than those of control mice. The numbers of hair follicles in the anagen phase of BP201-treated mice were also higher than those of control mice. In combination with MNX, BP201 further increased the total number of hair follicles, but did not alter the percentage of hair follicles in the anagenic phase. BP201 also increased the proliferation of human hair follicle dermal papilla cells. Collectively, BP201 possesses hair growth promoting potential, which would suggest its use singly or in combination for hair growth products.

Essential phospholipids as a supportive adjunct in the management of patients with NAFLD

Background and study aims: Treatment of nonalcoholic fatty liver [NAFLD] is important because NAFLD patients have a 1.7-fold increase in standardised age and gender matched mortality. Currently treatment is based on life style modification and managing comorbid associating disease. Other medications remain experimental. Essential phospholipid [EPL] is a nutrient for the liver, helping to maintain vitality of cell membranes where the vast majority of liver activities are regulated. We performed a randomised open label study to evaluate EPL as an adjuvant nutrient to the treatment of primary NAFLD or NAFLD with comorbid disease

Patients and method: Three groups of NAFLD patients were recruited: lone [n = 113], diabetes mellitus type 2 [n = 107] and mixed hyperlipidaemia [n = 104]. Diagnosis was established by excluding other chronic liver diseases. A standard diet and physical activity plan were advised to all patients. 1800 mg of EPL a day was given for 24 weeks, followed by 900 mg for 48 weeks

Results: Essential phospholipid EPL led to a significant improvement of symptoms and a mean reduction of ALT of 50.8 IU and AST of 46.1 IU per patient [p < 0.01]. Abdominal ultrasonography indicated normalisation in 4.6% and a shift from grade II to grade I in 24% of patients. Liver stiffness measurement indicated an improvement in 21.1%, with a mean reduction in the LSM of 3.1 K Pascal/patient. Reducing the dosage after six months led to a limited relapse in 43.8-63.2% of patients, for lone and NAFLD with co-morbid conditions

Conclusion: Essential phospholipid [EPL] as a nutritional supplement resulted in a significant improvement in clinical parameters and transaminases for all NAFLD patients. Ultrasound and LSM revealed modest improvement. There is a need for uninterrupted maintenance to avoid relapse

Sociodemographic and health factors associated with chronic pain in institutionalized elderly / Fatores sociodemográficos e de saúde associados à dor crônica em idosos institucionalizados / Factores sociodemográficos y de salud asociados al dolor crónico en ancianos institucionalizados

OBJECTIVES: to characterize chronic pain in institutionalized elderly and verify the associated factors. METHOD: observational, cross-sectional and non-experimental study with a quantitative approach. The study participants were 124 elderly living in Long-Term Care Institutions for the Elderly (LTCIs) in a city in Minas Gerais (Brazil). Approval for the project was obtained from the Research Ethics Committee. The elderly's clinical and sociodemographic variables and pain-related aspects were assessed. The data were analyzed through descriptive statistics and bivariate analysis (chi-squared). RESULTS: the prevalence of chronic pain corresponded to 58.1%; for more than 10 years (26.4%); in lower limbs (31.9%); characterized as "twinges" (33.3%); 33.3% adopted medication treatment; the pain did not improve (41.7 %); or worsen (34.7 %). It was evidenced that elderly aged 60├ 70 old had 70% less chances of chronic pain than those aged 80 years and older (p=0.018). CONCLUSION: institutionalized elderly have a high prevalence of chronic pain, mainly in the lower limbs. No factors of pain improvement or worsening were identified and medication was evidenced as the preferred treatment. Age showed to be associated with the presence of pain. It is considered important to accomplish multiprofessional actions at the LTCIs to guide prevention and rehabilitation actions of the pain episodes in these elderly. .

OBJETIVOS: caracterizar a dor crônica em idosos institucionalizados e verificar os fatores associados. MÉTODO: estudo observacional, transversal, não experimental, com abordagem quantitativa. Participaram do estudo 124 idosos residentes nas Instituições de Longa Permanência para Idosos de um município de Minas Gerais, Brasil. O projeto aprovado pelo Comitê de Ética e Pesquisa. Foram avaliadas variáveis clínicas e sociodemográficas dos idosos e aspectos relacionados à dor. Os dados foram analisados segundo estatística descritiva e análise bivariada (qui-quadrado). RESULTADOS: observou-se prevalência de 58,1% de dor crônica; por mais de 10 anos (26,4%); em membros inferiores (31,9%); do tipo "pontada" (33,3%); 33,3% adotavam tratamento medicamentoso; não havendo fator de melhora (41,7 %) ou piora da dor (34,7 %). Evidenciou-se que idosos com 60├70 anos tiveram 70% menos chances de apresentarem dor crônica em relação aos de 80 anos e mais (p=0,018). CONCLUSÃO: idosos institucionalizados possuíam prevalência alta de dor crônica, principalmente em membros inferiores, não se identificou o fator melhora ou piora da dor e o tratamento medicamentoso foi evidenciado como primeira escolha. A idade revelou-se fator associado à presença de dor. Considera-se importante que ações multiprofissionais sejam realizadas nas Instituições de Longa Permanência para Idosos, para direcionar ações de prevenção e reabilitação dos episódios de dor nesses idosos. .

OBJETIVOS: caracterizar el dolor crónico en ancianos institucionalizados y verificar los factores asociados. MÉTODO: estudio observacional, trasversal, no experimental, aproximación cuantitativa. Participaron del estudio 124 ancianos residentes en las Instituciones de Larga Permanencia para Ancianos (ILPAs) de un municipio de Minas Gerais (Brasil). Proyecto aprobado por el Comité de Ética e Investigación. Fueron evaluadas variables clínicas y sociodemográficas de los ancianos y aspectos relacionados al dolor. Los datos fueron analizados según estadística descriptiva y análisis bivariado (ji-cuadrado). RESULTADOS: fue observada prevalencia de 58,1% de dolor crónica; durante más de 10 años (26,4%); en miembros inferiores (31,9%); del tipo "punzada" (33,3%); 33,3% adoptaba tratamiento medicamentoso; sin factor de mejora (41,7 %); o empeoramiento del dolor (34,7%). Fue evidenciado que ancianos con 60├ 70 años tuvieron 70% menos chances de presentar dolor crónico con relación a aquellos de 80 años y más (p=0,018). CONCLUSIÓN: ancianos institucionalizados tenían prevalencia alta de dolor crónico, principalmente en miembros inferiores, no fue identificado el factor de mejora o empeoramiento del dolor y el tratamiento medicamentoso fue evidenciado como preferencia. La edad se mostró factor asociado a la presencia de dolor. Es considerado importante que acciones multiprofesionales sean llevadas a cabo en las ILPAs para dirigir acciones de prevención y rehabilitación de los episodios de dolor en esos ancianos. .

Bioactive Lysophosphatidylcholine 16:0 and 18:0 Are Elevated in Lungs of Asthmatic Subjects

PURPOSE: Asthma is a chronic inflammatory disease of the airways, and is associated with upregulation of phospholipase A2 (PLA2), the enzyme that hydrolyzes phosphatidylcholine, producing lysophosphatidylcholine (LPC) and free fatty acids. LPC is a lipid mediator with known pro-inflammatory and pro-atherogenic properties, and is believed to be a critical factor in cardiovascular diseases. We postulate that asthmatic subjects have an elevated content of LPC in the lung lining fluids. METHODS: Eight non-asthmatic controls and seven asthmatic subjects were recruited for broncho-alveolar lavage fluids (BALF) collection for analysis of LPC by high performance liquid chromatography-tandem mass spectrometry. RESULTS: LPC16:0 and LPC18:0 were significantly elevated in the BALF of asthmatics with impaired lung function characteristic of moderate asthma, but not mild asthma. The increased LPC content in BALF was accompanied by increased PLA2 activity. Furthermore, qRT-PCR analysis of the BALF cell fraction indicated increased secretory PLA2-X (sPLA2-X). CONCLUSIONS: The increased LPC content in the lung lining fluids is a potential critical lipid mediator in the initiation and/or progression of airway epithelial injury in asthma.

Stimulated Bronchial Epithelial Cells Release Bioactive Lysophosphatidylcholine 16:0, 18:0, and 18:1

PURPOSE: In human subjects and animal models with acute and chronic lung injury, the bioactive lysophosphatidylcholine (LPC) is elevated in lung lining fluids. The increased LPC can promote an inflammatory microenvironment resulting in lung injury. Furthermore, pathological lung conditions are associated with upregulated phospholipase A2 (PLA2), the predominant enzyme producing LPC in tissues by hydrolysis of phosphatidylcholine. However, the lung cell populations responsible for increases of LPC have yet to be systematically characterized. The goal was to investigate the LPC generation by bronchial epithelial cells in response to pathological mediators and determine the major LPC species produced. METHODS: Primary human bronchial epithelial cells (NHBE) were challenged by vascular endothelial growth factor (VEGF) for 1 or 6 h, and condition medium and cells collected for quantification of predominant LPC species by high performance liquid chromatography-tandem mass spectrometry (LC-MS-MS). The cells were analyzed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) for PLA2. The direct effects of LPC in inducing inflammatory activities on NHBE were assessed by transepithelial resistance as well as expression of interleukin-8 (IL-8) and matrix metalloproteinase-1 (MMP-1). RESULTS: VEGF stimulation of NHBE for 1 or 6 h, significantly increased concentrations of LPC16:0, LPC18:0, and LPC18:1 in condition medium compared to control. The sPLA2-selective inhibitor (oleyloxyethyl phosphorylcholine) inhibited the VEGF-induced release of LPC16:0 and LPC18:1 and PLA2 activity. In contrast, NHBE stimulated with TNF did not induce LPC release. VEGF did not increase mRNA of PLA2 subtypes sPLA2-X, sPLA2-XIIa, cPLA2-IVa, and iPLA2-VI. Exogenous LPC treatment increased expression of IL-8 and MMP-1, and reduced the transepithelial resistance in NHBE. CONCLUSIONS: Our findings indicate that VEGF-stimulated bronchial epithelial cells are a key source of extracellular LPCs, which can function as an autocrine mediator with potential to induce airway epithelial inflammatory injury.

comparison of the effects of silybin and silybin-phosphatidylcholine on viability and ESR expression in human breast cancer T47D cell line

Silybin is a polyphenol with anti-oxidant and anti-cancer properties. The poor bioavailability of some polyphenols can be improved by binding to phosphatidylcholine. In recent years, studies have been conducted to evaluate the anti-cancer effect of silybin. We studied the effect of silybin and silybin-phosphatidylcholine on ESR1 and ESR2 gene expression and viability in the T47D breast cancer cell line. In this experimental study, a 3-[4,5-Dimethylthiazol-2-Yl]-2,5- Diphenyltetrazolium Bromide test [MTT test] was used to determine doses for cell treatment, and the gene expression was analyzed by real-time reverse transcriptase-polymerase chain reaction [real-time RT- PCR]. Significant dose- and time-dependent cell growth inhibitory effects of silybin and silybin-phosphatidylcholine along with ESR1 down-regulation were observed in T47D cells. In contrast to ESR1, the T47D cell line showed negligible ESR2 expression. This study suggests that silybin and silybin-phosphatidylcholine down-regulate ESR1 in ER+ breast cancers. Results also show that in the T47D cell line, silybinphosphatidylcholine has a much higher growth inhibitory effect and a more significant down-regulation of ESR1 compared with silybin

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.

Antioxidant effect of 4-nerolidylcatechol and -tocopherol in erythrocyte ghost membranes and phospholipid bilayers

4-Nerolidylcatechol (4-NC) is found in Pothomorphe umbellata root extracts and is reported to have a topical protective effect against UVB radiation-induced skin damage, toxicity in melanoma cell lines, and antimalarial activity. We report a comparative study of the antioxidant activity of 4-NC and α-tocopherol against lipid peroxidation initiated by two free radical-generating systems: 2,2′-azobis(2-aminopropane) hydrochloride (AAPH) and FeSO4/H2O2, in red blood cell ghost membranes and in egg phosphatidylcholine (PC) vesicles. Lipid peroxidation was monitored by membrane fluidity changes assessed by electron paramagnetic resonance spectroscopy of a spin-labeled lipid and by the formation of thiobarbituric acid-reactive substances. When lipoperoxidation was initiated by the hydroxyl radical in erythrocyte ghost membranes, both 4-NC and α-tocopherol acted in a very efficient manner. However, lower activities were observed when lipoperoxidation was initiated by the peroxyl radical; and, in this case, the protective effect of α-tocopherol was lower than that of 4-NC. In egg PC vesicles, malondialdehyde formation indicated that 4-NC was effective against lipoperoxidation initiated by both AAPH and FeSO4/H2O2, whereas α-tocopherol was less efficient in protecting against lipoperoxidation by AAPH, and behaved as a pro-oxidant for FeSO4/H2O2. The DPPH (2,2-diphenyl-1-picrylhydrazyl) free-radical assay indicated that two free radicals were scavenged per 4-NC molecule, and one free radical was scavenged per α-tocopherol molecule. These data provide new insights into the antioxidant capacity of 4-NC, which may have therapeutic applications for formulations designed to protect the skin from sunlight irradiation.

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.

Development of SCAR Markers for the Identification of Phytophthora katsurae Causing Chestnut Ink Disease in Korea

Sequence characterized amplified region (SCAR) markers are one of the most effective and accurate tools for microbial identification. In this study, we applied SCAR markers for the rapid and accurate detection of Phytophthora katsurae, the casual agent of chestnut ink disease in Korea. In this study, we developed seven SCAR markers specific to P. katsurae using random amplified polymorphic DNA (RAPD), and assessed the potential of the SCAR markers to serve as tools for identifying P. katsurae. Seven primer pairs (SOPC 1F/SOPC 1R, SOPC 1-1F/SOPC 1-1R, SOPC 3F/SOPC 3R, SOPC 4F/SOPC 4R, SOPC 4F/SOPC 4-1R, SOPD 9F/SOPD 9R, and SOPD 10F/SOPD 10R) from a sequence derived from RAPD fragments were designed for the analysis of the SCAR markers. To evaluate the specificity and sensitivity of the SCAR markers, the genomic DNA of P. katsurae was serially diluted 10-fold to final concentrations from 1 mg/mL to 1 pg/mL. The limit of detection using the SCAR markers ranged from 100 microg/mL to 100 ng/mL. To identify the limit for detecting P. katsurae zoospores, each suspension of zoospores was serially diluted 10-fold to final concentrations from 10 x 10(5) to 10 x 10(1) zoospores/mL, and then extracted. The limit of detection by SCAR markers was approximately 10 x 10(1) zoospores/mL. PCR detection with SCAR markers was specific for P. katsurae, and did not produce any P. katsurae-specific PCR amplicons from 16 other Phytophthora species used as controls. This study shows that SCAR markers are a useful tool for the rapid and effective detection of P. katsurae.

Monitoring of chemical components with different color traits of Tussilago farfara using NMR-based metabolomics / 药学学报

The quality and grade of traditional Chinese medicinal herbs were assessed by their characteristics traditionally. According to traditional experience, the quality of the purple Flos Farfarae is better than that of yellow buds. NMR-based metabolomic approach combined with significant analysis of microarray (SAM) and Spearman rank correlation analysis were used to investigate the different metabolites of the Flos Farfarae with different color feature. Principal component analysis (PCA) showed clear distinction between the purple and yellow flower buds of Tussilago farfara. The S-plot of orthogonal PLS-DA (OPLS-DA) and t test revealed that the levels of threonine, proline, phosphatidylcholine, creatinine, 4, 5-dicaffeoylquinic acid, rutin, caffeic acid, kaempferol analogues, and tussilagone were higher in the purple flower buds than that in the yellow buds, in agreement with the results of SAM and Spearman rank correlation analysis. The results confirmed the traditional medication experience that "purple flower bud is better than the yellow ones", and provide a scientific basis for assessing the quality of Flos Farfarae by the color features.

Advent of Novel Phosphatidylcholine-Associated Nonsteroidal Anti-Inflammatory Drugs with Improved Gastrointestinal Safety

The mucosa of the gastrointestinal (GI) tract exhibits hydrophobic, nonwettable properties that protect the underlying epithelium from gastric acid and other luminal toxins. These biophysical characteristics appear to be attributable to the presence of an extracellular lining of surfactant-like phospholipids on the luminal aspects of the mucus gel layer. Phosphatidylcholine (PC) represents the most abundant and surface-active form of gastric phospholipids. PC protected experimental rats from a number of ulcerogenic agents and/or conditions including nonsteroidal anti-inflammatory drugs (NSAIDs), which are chemically associated with PC. Moreover, preassociating a number of the NSAIDs with exogenous PC prevented a decrease in the hydrophobic characteristics of the mucus gel layer and protected rats against the injurious GI side effects of NSAIDs while enhancing and/or maintaining their therapeutic activity. Bile plays an important role in the ability of NSAIDs to induce small intestinal injury. NSAIDs are rapidly absorbed from the GI tract and, in many cases, undergo enterohepatic circulation. Thus, NSAIDs with extensive enterohepatic cycling are more toxic to the GI tract and are capable of attenuating the surface hydrophobic properties of the mucosa of the lower GI tract. Biliary PC plays an essential role in the detoxification of bile salt micelles. NSAIDs that are secreted into the bile injure the intestinal mucosa via their ability to chemically associate with PC, which forms toxic mixed micelles and limits the concentration of biliary PC available to interact with and detoxify bile salts. We have worked to develop a family of PC-associated NSAIDs that appear to have improved GI safety profiles with equivalent or better therapeutic efficacy in both rodent model systems and pilot clinical trials.

Protective Effect of Phosphatidylcholine on Lipopolysaccharide-Induced Acute Inflammation in Multiple Organ Injury

Soybean polyunsaturated phosphatidylcholine (PC) is thought to exert anti-inflammatory activities and has potent effects in attenuating acute renal failure and liver dysfunction. The aim of this study was to investigate the effects of PC in protecting multiple organ injury (MOI) from lipopolysaccharide (LPS). Six groups of rats (N=8) were used in this study. Three groups acted as controls and received only saline, hydrocortisone (HC, 6 mg/kg, i.v.) or PC (600 mg/kg, i.p.) without LPS (15 mg/kg, i.p.) injections. Other 3 groups, as the test groups, were administered saline, HC or PC in the presence of LPS. Six hours after the LPS injection, blood and organs (lung, liver and kidney) were collected from each group to measure inflammatory cytokines and perform histopathology and myeloperoxidase (MPO) assessment. Serum cytokines (TNF-alpha, IL-6 and IL-10) and MPO activities were significantly increased, and significant histopathological changes in the organs were observed by LPS challenge. These findings were significantly attenuated by PC or HC. The treatment with PC or HC resulted in a significant attenuation on the increase in serum levels of TNF-alpha and IL-6, pro-inflammatory cytokines, while neither PC nor HC significantly attenuated serum levels of IL-10, anti-inflammatory cytokine. In the organs, the enhanced infiltration of neutrophils and expression of ED2 positive macrophage were attenuated by PC or HC. Inductions of MPO activity were also significantly attenuated by PC or HC. From the findings, we suggest that PC may be a functional material for its use as an anti-inflammatory agent.