Chemical Investigation on an Endophytic fungus Gibberella moniliformis JS1055 Derived from a Halophyte Vitex rotundifolia

Chemical investigation of the ethyl acetate extract of Gibberella moniliformis JS1055 endophytic fungus derived from a halophyte, Vitex rotundifolia, led to the isolation of nine compounds including 7-butyl-6,8-dihydroxy-3(R)-pent-11-enylisochroman-1-one (1), 7-butyl-6,8-dihydroxy-3(R)-pentylisochroman-1-one (2), 7-butyl-6,8-dihydroxy-3(R)-pentylisochroman-1-one (3), 5α,8α-epidioxyergosta-6,9(11),22-trien-3-ol (4), ergosterol peroxide (5), tetradecanoic acid (6), 8-O-methylfusarubin (7), nicotinic acid (8) and adenosine (9). They were identified by extensive spectroscopic data analysis including 1D, 2D (¹H-¹H COSY, HSQC, HMBC) NMR, and ESIMS. All the isolates (1

Inhibitory Effects of CD99-derived Peptide CD99CRIII3 on the Extravasation of Monocytes and Inflammatory Reactions in Contact Dermatitis Mouse Model / 체질인류학회지

Leucocyte extravasation has been known to play an important role in inflammatory reactions including contact dermatitis. Previous studies suggested that CD99 regulates β1 integrin activity and may be a novel therapeutic target molecule for inflammatory diseases. In this study, the effects of CD99-derived peptide, CD99CRIII3, on inflammatory reactions in contact dermatitis mouse model were investigated. CD99CRIII3 decreased β1-integrin activity in human monocytic U937 cells. CD99CRIII3 inhibited the adhesion of U937 monocytes to human umbilical vein endothelial cells and their extravasation through human umbilical vein endothelial cells. CD99CRIII3 reduced inflammation in the phorbol myristate acetate-induced contact dermatitis mice in a dose-dependent manner. These results indicate that CD99CRIII3 suppresses the extravasation of monocytes and inflammatory reactions in the animal model of the contact dermatitis, suggesting that CD99CRIII3 could be a new drug candidate against inflammatory skin diseases.

Serum myristic fatty acid negatively correlates with anti-inflammatory adiponectin/leptin ratio in obese adolescents: effects of long- term therapy / O ácido graxo mirístico sérico correlaciona-se negativamente com a razão adiponectina/leptina anti-inflamatória em adolescentes obesos: efeitos da terapia de longo prazo

Obesity is related to metabolic disorders partially mediated by inflammatory state. In this way, adiponectin/leptin ratio is considered an anti-inflammatory biomarker related to cardiovascular risks. Evidence suggest that decrease in saturated fatty acid intake is an important dietary recommendation to reduce cardiovascular risk factors. Thus, the purpose of the present study was to evaluate if serum myristic fatty acid can modulate metabolic profile and inflammatory process in obese adolescents after weight-loss therapy. Twenty-nine obese post-pubertal obese adolescents, aged 14 to 19 years, were submitted to the long-term interdisciplinary treatment, including physical exercise, clinic, nutritional and psychological intervention. The blood samples were collected to glycaemia, insulin, lipid profile, leptin and adiponectin analysis. Serum fatty acid composition was performed by technical of chromatography in fizzy phase. The therapy promoted significant improvement in body mass, BMI, subcutaneous and visceral fat, insulin, lipid profile, leptin and leptin/adiponectin ratio. Significant decrease in myristic fatty acid was observed. Simple linear regression analysis showed that myristic fatty acid was positively associated with changes in triglycerides and very low density lipoprotein cholesterol, and was negatively associated with adiponectin/leptin ratio. In summary, we observed that long-term weight loss therapy was effective to improve metabolic/inflammatory profile and serum myristic fatty acid. Moreover, our results suggested the relation between changes in serum myristic fatty acids with the anti-inflammatory adiponectin/ leptin ratio, which may modulate metabolic and inflammatory process related to obesity

A obesidade está relacionada a distúrbios metabólicos parcialmente mediados por um estado inflamatório. Desta forma, a razão a diponectina/leptina é considerada um biomarcador anti-inflamatório relacionado aos riscos cardiovasculares. Evidências sugerem que a diminuição na ingestão de ácidos graxos saturados seja uma recomendação dietética importante para reduzir os fatores de risco cardiovascular. Assim, o objetivo do presente estudo foi avaliar se o ácido graxo mirístico sérico pode modular o perfil metabólico e processos inflamatórios em adolescentes obesos após a terapia para perda de peso. Vinte e nove adolescentes pós-púberes e obesos de 14 a 19 anos de idade foram submetidos a um tratamento interdisciplinar de longo prazo, incluindo exercício físico, intervenção clínica, nutricional e psicológica. As amostras de sangue foram coletadas para análise da glicemia, insulina, perfil lipídico, leptina e adiponectina. A composição de ácidos graxos séricos foi realizada por técnicas de cromatografia em fase gasosa. A terapia promoveu uma melhora significativa na massa corporal, IMC, gordura subcutânea e visceral, insulina, perfil lipídico, leptina e a razão leptina/adiponectina. Observou-se uma diminuição significativa na concentração sérica de ácido graxo mirístico. A análise de regressão linear simples mostrou que o ácido graxo mirístico foi positivamente associado a alterações nos triglicerídeos e colesterol de lipoproteínas de muito baixa densidade e foi associado negativamente à proporção de adiponectina/leptina. Em resumo, observamos que a terapia de perda de peso a longo prazo foi efetiva na melhora do perfil metabólico/inflamatório e do ácido graxo mirístico sérico. Além disso, nossos resultados sugerem uma relação entre as alterações no ácido graxo mirístico séricos e a razão adiponectina/leptina antiinflamatória, que podem modular processos metabólicos e inflamatórios relacionados à obesidade

Characterization of a Biflaviolin Synthase CYP158A3 from Streptomyces avermitilis and Its Role in the Biosynthesis of Secondary Metabolites

Streptomyces avermitilis produces clinically useful drugs such as avermectins and oligomycins. Its genome contains approximately 33 cytochrome P450 genes and they seem to play important roles in the biosynthesis of many secondary metabolites. The SAV_7130 gene from S. avermitilis encodes CYP158A3. The amino acid sequence of this enzyme has high similarity with that of CYP158A2, a biflaviolin synthase from S. coelicolor A3(2). Recombinant S. avermitilis CYP158A3 was heterologously expressed and purified. It exhibited the typical P450 Soret peak at 447 nm in the reduced CO-bound form. Type I binding spectral changes were observed when CYP158A3 was titrated with myristic acid; however, no oxidative product was formed. An analog of flaviolin, 2-hydroxynaphthoquinone (2-OH NQ) displayed similar type I binding upon titration with purified CYP158A3. It underwent an enzymatic reaction forming dimerized product. A homology model of CYP158A3 was superimposed with the structure of CYP158A2, and the majority of structural elements aligned. These results suggest that CYP158A3 might be an orthologue of biflaviolin synthase, catalyzing C-C coupling reactions during pigment biosynthesis in S. avermitilis.

Matrix Degradative Enzymes and Their Inhibitors during Annular Inflammation: Initial Step of Symptomatic Intervertebral Disc Degeneration

OBJECTIVE: Symptomatic disc degeneration develops from inflammatory reactions in the annulus fibrosus (AF). Although inflammatory mediators during annular inflammation have been studied, the roles of matrix metalloproteinases (MMPs) and their inhibitors have not been fully elucidated. In this study, we evaluated the production of MMPs and tissue inhibitors of metalloproteinase (TIMPs) during annular inflammation using an in vitro co-culture system. We also examined the effect of notochordal cells on annular inflammation. METHODS: Human AF (hAF) pellet was co-cultured for 48 hours with phorbol myristate acetate-stimulated macrophage-like THP-1 cells. hAF pellet and conditioned media (CM) from co-cultured cells were assayed for MMPs, TIMPs, and insulin-like growth factor (IGF)-1 levels using real-time reverse-transcriptase polymerase chain reaction and enzyem-linked immunosorbent assay. To evaluate whether notochordal cells affected MMPs or TIMPs production on annular inflammation, hAF co-cultured with notochordal cells from adult New Zealand White rabbits, were assayed. RESULTS: MMP-1, -3, -9; and TIMP-1 levels were significantly increased in CM of hAF co-cultured with macrophage-like cells compared with hAF alone, whereas TIMP-2 and IGF-1 levels were significantly decreased (p<0.05). After macrophage exposure, hAF produced significantly more MMP-1 and -3 and less TIMP-1 and -2. Interleukin-1beta stimulation enhanced MMP-1 and -3 levels, and significantly diminished TIMP-2 levels. Co-culturing with rabbit notochordal cells did not significantly influence MMPs and TIMPs production or COL1A2 gene expression. CONCLUSION: Our results indicate that macrophage-like cells evoke annular degeneration through the regulation of major degradative enzymes and their inhibitors, produced by hAF, suggesting that the selective regulation of these enzymes provides future targets for symptomatic disc degeneration therapy.

Modificaciones de las lipoproteínas del plasma en voluntarios sometidos a dietas preparadas con aceite de girasol solo o mezclado con oleína de palma / Changes in the content of plasma lipoproteins in persons subjected to diets prepared with sunflower oil alone or mixed with palm olein

En 31 comensales regulares del Comedor Universitario de la Universidad Central de Venezuela (CUUCV), en Caracas. Se observó el efecto de la sustitución del aceite de girasol que se utiliza corrientemente en la preparación de las comidas en ese comedor, por un aceite obtenido de la mezcla de aceite de girasol y oleína de palma, en la proporción 70/30 (v/v) respectivamente. Después de 40 días continuos de la sustitución no hubo cambios significativos en las concentraciones de colesterol total (CT), ni del colesterol de las lipoproteínas de baja densidad (LDL) y muy baja densidad (VLDL). La concentración del colesterol de las lipoproteínas de alta densidad (HDL) aumentó significativamente (p<0,05). Los triglicéridos (TG) del plasma aumentaron en un 30%. La resistencia a la oxidación de las LDL aumentó considerablemente (p< 0,01). Hoy se considera a esta resistencia como un factor protector de gran importancia en la prevención del inicio del proceso aterogénico. Tomando en cuenta las modificaciones favorables como el aumento de colesterol de HDL sin modificación de la LDL y el claro aumento de la resistencia a la oxidación de la LDL, se considera que la oleína de palma es un aceite vegetal que puede ser utilizado sin mayores riesgos en mezcla con otros aceites que tengan una relación linoleico/palmítico más elevada como los aceites de girasol, maíz, soja y otros.

We analyzed in 31 subjects, regular guests of the University food service of the Central University of Venezuela (UCVFS), in Caracas, the effects of replacing sunflower oil, commonly used in the preparation of meals, by a mix of sunflower oil and palm olein 70/30 (v/v) respectively. Plasma concentrations of total cholesterol, low and very low density lipoproteins were not changed after 40 days of the substitution. On the contrary, concentrations of high density lipoprotein and total triglycerides increased. The resistance to the oxidation of low-density lipoproteins increased considerably (p<0, 01). Today this resistance is considered as a protective factor of great importance in the prevention of the initiation of the atherogenic process. Taking into account the favorable modifications of HDL cholesterol and the clear increased resistance to the oxidation of LDL, we think that palm olein, mixed with other oils with a high ratio linoleic/palmític (sunflower, corn, soya an the likes), can be used as a healthy alternative in human nutrition.

Evaluation of Expression of Lipases and Phospholipases of Malassezia restricta in Patients with Seborrheic Dermatitis

BACKGROUND: Malassezia species (spp.) are cutaneous opportunistic pathogens and associated with various dermatological diseases including seborrheic dermatitis, dandruff and atopic dermatitis. Almost all Malassezia spp. are obligatorily lipid-dependent, which might be caused by lack of the myristic acid synthesis. Recent genome analysis of M. restricta and M. globosa suggested that the absence of a gene encoding fatty acid synthesis might be compensated by abundant genes encoding hydrolases, which produce fatty acids, and that lipases and phospholipases may play a role in virulence of the fungus. OBJECTIVE: The current study aimed to investigate the contribution of lipases and phospholipases in virulence of the M. restricta as being the most frequently isolated Malassezia spp. from the human skin. METHODS: Swap samples of two different body sites of at least 18 patients with seborrheic dermatitis were obtained and in vivo expression of lipases and phospholipases of M. restricta was analyzed by the gene specific two-step nested RT-PCR. RESULTS: The results of the current study suggest that majority of the patients display expression of lipase RES_0242. CONCLUSION: These data imply a possible role of lipase in the host environment to produce free fatty acids for the fungus.

Evaluation of Expression of Lipases and Phospholipases of Malassezia restricta in Patients with Seborrheic Dermatitis

BACKGROUND: Malassezia species (spp.) are cutaneous opportunistic pathogens and associated with various dermatological diseases including seborrheic dermatitis, dandruff and atopic dermatitis. Almost all Malassezia spp. are obligatorily lipid-dependent, which might be caused by lack of the myristic acid synthesis. Recent genome analysis of M. restricta and M. globosa suggested that the absence of a gene encoding fatty acid synthesis might be compensated by abundant genes encoding hydrolases, which produce fatty acids, and that lipases and phospholipases may play a role in virulence of the fungus. OBJECTIVE: The current study aimed to investigate the contribution of lipases and phospholipases in virulence of the M. restricta as being the most frequently isolated Malassezia spp. from the human skin. METHODS: Swap samples of two different body sites of at least 18 patients with seborrheic dermatitis were obtained and in vivo expression of lipases and phospholipases of M. restricta was analyzed by the gene specific two-step nested RT-PCR. RESULTS: The results of the current study suggest that majority of the patients display expression of lipase RES_0242. CONCLUSION: These data imply a possible role of lipase in the host environment to produce free fatty acids for the fungus.

Effect of Apocynin on Acute Lung Injury in Rats Given Interleukin-1alpha Intratracheally / 결핵및호흡기질환

BACKGROUND: Based on the assertion that apocynin diminishes acute lung injury (ALI) by inhibition of NADPH oxidase, the effect of apocynin was tested in interleukin-1alpha (IL-1)-induced ALI in rats. METHODS: IL-1 was insufflated into the trachea of Sprague-Dawley rats to induce ALI, and apocynin (8 mg/kg) was given intravenously for inhibition of NADPH oxidase. In addition, we determined whether apocynin inhibited generation of superoxide anions from isolated human neutrophils. Five hours after IL-1 instillation, lung injury parameters, expression of cytosolic phospholipase A2 (cPLA2) by cells from bronchoalveolar lavage (BAL), an index of oxidative stress in lung tissues (gamma-glutamyltranspeptidase, activity), and ultrastructure of alveolar type II (AT II) cells were evaluated. RESULTS: Apocynin decreased the generation of free radicals from phorbol myristate (PMA)-activated neutrophils in vitro, but did not ameliorate ALI. IL-1 induced enhancement of the expression of cPLA2 on neutrophils was not altered by apocynin. CONCLUSION: Apocynin induced suppression of the generation of superoxide anions from neutrophils by inhibition of NADPH oxidase does not attenuate IL-1-induced ALI in rats.

Molecular Identification of the Vaccine Strain from the Inactivated Rabies Vaccine

Since 1994, several different inactivated rabies vaccines have been used to immunize domestic animals such as dogs, cats, and cattle in South Korea. The Korean Veterinary Authority has conducted safety and efficacy testes of inactivated vaccines using laboratory animals. In this study, we applied a molecular method to investigate the genetic characterization of the rabies virus (RABV) genes in six commercial inactivated rabies vaccines, and determined the efficiency of two extraction reagents (i.e., sodium citrate or isopropyl myristate) to separate the vaccine antigens from the antigen/adjuvant complexes. Six partial nucleocapsid (N: 181 bp) and five partial glycoprotein (G: 306 bp) genes were successfully amplified with specific primer sets, which demonstrated that sodium citrate is more efficient than isopropyl myristate in extracting viral RNA from inactivated gel vaccines. In addition, we identified the viral strain of the vaccine by analyzing the nucleotide sequences of the N and the G genes. The nucleotide similarity of the partial N and G genes ranged from 97.1 to 99.4% and from 91.8 to 100% among rabies vaccine strains, respectively, indicating that each manufacturer used different rabies virus strains to produce their vaccines. The molecular method used in this study could also be used to identify viral strains in other inactivated vaccines.

Chain length-dependent cooperativity in fatty acid binding and oxidation by cytochrome P450BM3 (CYP102A1)

Fatty acid binding and oxidation kinetics for wild type P450(BM3) (CYP102A1) from Bacillus megaterium have been found to display chain length-dependent homotropic behavior. Laurate and 13-methyl-myristate display Michaelis-Menten behavior while there are slight deviations with myristate at low ionic strengths. Palmitate shows Michaelis-Menten kinetics and hyperbolic binding behavior in 100 mmol/L phosphate, pH 7.4, but sigmoidal kinetics (with an apparent intercept) in low ionic strength buffers and at physiological phosphate concentrations. In low ionic strength buffers both the heme domain and the full-length enzyme show complex palmitate binding behavior that indicates a minimum of four fatty acid binding sites, with high cooperativity for the binding of the fourth palmitate molecule, and the full-length enzyme showing tighter palmitate binding than the heme domain. The first flavin-to-heme electron transfer is faster for laurate, myristate and palmitate in 100 mmol/L phosphate than in 50 mmol/L Tris (pH 7.4), yet each substrate induces similar high-spin heme content. For palmitate in low phosphate buffer concentrations, the rate constant of the first electron transfer is much larger than k (cat). The results suggest that phosphate has a specific effect in promoting the first electron transfer step, and that P450(BM3) could modulate Bacillus membrane morphology and fluidity via palmitate oxidation in response to the external phosphate concentration.

Contenidos de aceite y de los ácidos láurico y mirístico en frutos maduros de Roystonea regia colectados durante dos años / Oily contents and the lauric and myristic acids in mature fruits of Roystonea regia harvested for two year

INTRODUCCIÓN: el D004, un ingrediente activo promisorio en el tratamiento de la hiperplasia prostática benigna, se obtiene a partir del aceite del fruto de Roystonea regia (Kunth) OF Cook. Está compuesto por una mezcla de ácidos grasos libres que incluye los ácidos láurico y mirístico, ambos de gran interés por sus efectos farmacológicos. OBJETIVO: determinar la posible influencia de la época de colecta sobre el contenido de aceite y la concentración de los ácidos láurico y mirístico de los frutos de R regia. MÉTODOS: se colectaron cada mes, durante 2 años, frutos maduros de R regia en una población seleccionada. En las muestras secas y molidas se determinó el contenido de aceite gravimétricamente y el de ácidos grasos por cromatografía de gases. RESULTADOS: se encontraron diferencias estadísticas significativas en los contenidos de aceite y de los ácidos láurico y mirístico; no obstante, los contenidos determinados en todos los casos se mantuvieron dentro de las especificaciones calidad establecidas para el material vegetal. CONCLUSIONES: el material vegetal colectado durante todo el año puede ser empleado en la obtención del aceite de R. regia, materia prima empleada en la producción de D004

INTRODUCTION: D004, an promissory active ingredient in treatment and prevention of begnin prostatic hyperplasia, is obtained from the fruit oil of Roystonea regia (Kunth) OF Cook. It is composed by a mixture of free fatty acids including lauric and myristic acids, both very important by their pharmacological effects. OBJECTIVE: to determine the potential influence of harvest season on the oily content and the concentration of lauric and myristic acids from R regia fruits. METHODS: each month for two years, it was possible to collect mature fruits from R regia in a selected group. In dry and milled samples it was determined the oily content in a gravimetric way and that of fatty acids by gas chromatography. RESULTS: there were differences statistically significant in oily contents and of lauric and myristic acids; however, the contents determined in all the cases remained within the quality specifications established for the plant material. CONCLUSIONS: the plant material collected for all the year may be used in obtaining of R. regia oil, raw material used in the production of D004

A Case of Allergic Contact Dermatitis from Silmazine(R) Cream / 대한피부과학회지

Silmazine(R) cream is an antibiotic agent widely used in burn therapy. It consists of Propylene glycol, Stearyl alcohol, Isopropyl Myristate, Sorbitan mono-oleate, Methyl-p-hydroxybenzoate, Polyoxyl 40 stearate and varseline. A 24-year- old female presented with well-demarcated erythematous papules and vesicles with an itching sensation on the dorsal area of her right hand. She had applied Silmazine(R) cream on the dorsal area of her right handfor 4 days and the skin lesion became aggravated. A patch test with Silmazine(R) cream 'as is' showed a positive reaction and propylene glycol and stearyl alcohol, ingredients in Silmazine(R) cream, revealed a positive reaction. These two agents are known as weak sensitizers that can produce allergic contact dermatitis. There are some reports of allergic contact dermatitis from propylene glycol and stearyl alcohol used topically. As far as we know, there are no reports of allergic contact dermatitis from propylene glycol and stearyl alcohol in the Silmazine(R) cream (Silver sulfadiazine) that is commonly used as topical antibiotic medication for burns. We report this rare case of allergic contact dermatitis from propylene glycol and stearyl alcohol in Silmazine(R) cream (Silver sulfadiazine).

Conteúdo de miristicina em preparados de noz moscada (myristica fragans, Houtt) / Myristicin contents in nutmeg (Myristica fragans, Houtt) preparations

O objetivo deste trabalho foi de estabelecer um procedimento para determinar os teores de miristicina em sementes, óleo essencial e extrato aquoso de noz-moscada, com a finalidade de avaliar as propriedades benéficas e/ou tóxicas desta semente. As amostras de noz-moscada em pó e de semente foram coletadas nas regiões sul e sudeste do Brasil. A composição das frações, umidade, proteína, extrato etéreo, cinzas foi determinada conforme a AOAC. A miristicina foi determinada nas amostras de sementes, na fração lipídica e nos respectivos extratos hidrotérmicos e na infusão por meio de cromatografia gasosa. As sementes de noz-moscada comercializadas na forma de pó apresentaram maior variabilidade em sua composição centesimal, especialmente demonstrada pelo teor de nitrogênio (6 a 12%) e extrato etéreo (15 a 36%). O procedimento proposto para determinar miristicina mostrou a melhor performance quando a determinação foi realizada no extrato hidrotérmico da fração lipídica extraída a frio, sendo a recuperação de 88%, o coeficiente de variação 9% e o limite de quantificação de 3 mg/g de amostra. Os maiores teores de miristicina foram encontrados no extrato hidroalcoólico da fração lipídica das sementes e do pó de noz-moscada, respectivamente de 37 e 22 mg/g de amostra.

Toxicological efficacy of some indigenous dill compounds against the flesh fly, parasarcophaga dux thomson

In this study, the effect of the LC50 of the three isolated compounds [apiol, myristicin and d-carvone] from dill, Anethum graveolens, on the growth and reproduction of Parasarcophaga dux showed that the three compounds, especially apiol, caused a significant reduction in the percentage of adults emergence and females fecundity. The temperature toxicity relation shape of the three compounds and five insect growth regulations [methoprene, hydroprene, teflubenzuron, chlorfluazuron and precocene I] alone or in combination against P. dux was studied and discussed

Enzyme activity in the flesh fly parasarcophaga dux thomson influenced by dill compounds, myristicin and apiol

In this study, the newly emerged adults of Parasarcophaga dux were treated topically with various doses of myristicin and apiol isolated from roots of dill plant, Anethum graveolens. The compounds toxicity and the dehydrogenase activities of the treated stage and its subsequent developmental stages were studied. The results indicated that apiol is more toxic than myristicin. The spectrophotometric evaluation exhibited changes in the dehydrogenase activities after treatments. Compounds increased the activities of both alpha- glycerophosphate [GPDH] and malate dehydrogenase [MDH] in first half of metamorphosis [immature stages]. But, the level of malic enzyme [ME] activities of the various stages was obviously decreased

Effect of Defibrotide on Rat Reflux Esophagitis

This study was aimed at evaluating the effect of defibrotide on the development of the surgically induced reflux esophagitis, on gastric secretion, lipid peroxidation, polymorphonuclear leukocytes (PMNs) accumulation, polymorphonuclear leukocytes adherence, superoxide anion and hydrogen peroxide production in PMNs, scavenge of hydroxyl radical and hydrogen peroxide, cytokine (interleukin-1beta, tumor necrosis factor-alpha) production in blood, and intracellular calcium mobilization in PMNs. Defibrotide did not inhibit the gastric secretion and not change the gastric pH. Treatment of esophagitis rats with defibrotide inhibited lipid peroxidation, and myeloperoxidase (MPO) in the esophagus in comparison with untreated rats. Defibrotide significantly decreased the PMN adherence to superior mesenteric artery endothelium in a dose-dependent manner. Superoxide anion and hydrogen peroxide production in 1microM formylmethionylleucylphenylalanine (fMLP) - or 0.1microgram/ml N-phorbol 12- myristate 13-acetate (PMA) -activated PMNs was inhibited by defibrotide in a dose-dependent fashion. Defibrotide effectively scavenged the hydrogen peroxide but did not scavenge the hydroxyl radical. Treatment of esophagitis rats with defibrotide inhibited interleukin-1beta production in the blood in comparison with untreated rats, but tumor necrosis factor-alpha production was not affected by defibrotide. The fMLP-induced elevation of intracellular calcium in PMNs was inhibited by defibrotide. The results of this study suggest that defibrotide may have partly beneficial protective effects against reflux esophagitis by the inhibition lipid peroxidation, PMNs accumulation, PMNs adherence to endothelium, reactive oxygen species production in PMNs, inflammatory cytokine production (i.e. interleukin-1beta), and intracellular calcium mobilization in PMNs in rats.

The Relationship between Serum Cholesterol Levels and Dietary Fatty Acid Patterns, Plasma Fatty Acids, and Other Lipid Profile among Korean Adults / 대한지역사회영양학회지

The purposes of this research were to assess dietary fatty acid patterns and to elucidate the relationship between the serum cholesterol levels and dietary fatty acid patterns, plasma fatty acid compositions, BMI (body mass index), and other lipid profile. The subjects were 151 adults aged 23 to 80 years, selected from the Outpatient Clinic and Cardiovascular Department of the Seoul Municipal Hospital. Dietary data were obtained using three day food records. Sixteen dietary fatty acids were analyzed using Korean and US nutrient databases. The subjects were divided into three serum cholesterol levels: desirable ( or = 200 - or = 240 mg/dl, N = 72) groups. The high-risk group had higher BMI, waist, and waist to hip ratio (WHR) than the desirable and borderline-risk groups. Serum concentrations of triglyceride, LDL cholesterol and LDL/HDL cholesterol ratio were significantly higher in the high-risk group as compared to those in the other two groups. The serum cholesterol levels were highly correlated with BMI (r = 0.435), triglyceride (r = 0.425) and LDL/HDL cholesterol (r = 0.870) ratio. The highest fatty acid intake was from oleic acid (33 - 34% of total fatty acid intakes), which was followed by linoleic acid (27%), palmitic acid (19%), and stearic acid (7%). There was no correlation between the serum cholesterol levels and the dietary fatty acid intakes, polyunsaturated/monounsaturated/saturated fatty acids (P/M/S) and omega6/omega3 ratios. The correlation between plasma fatty acids such as myristic acid, oleic acid, linoleic acid, and docosahexaenoic acid and serum cholesterol levels was also weak.

Protective Effect of PKC and Nitric Oxide Affecting Taxol-Induced Cytotoxicity in C6-Gial Cells / 대한해부학회지

Paclitaxel (Taxol) is known as effective drug for inhibition of cell cycle encouraging in human cancer cells. This drug named an antimicrotubule agent which simulate the mitotic arrest towards an apoptosis. The influence of phorbol 12 myristate 13 acetate (PMA) activated protein kinase C (PKC) and nitric oxide (NO) on taxol-induced apoptosis, is poorly understood. To investigate the effects of PMA and NO on the signal transduction in taxol-induced apoptosis in C6-glial cells, the viability and caspase-3 activity of C6-glial cells were analyzed. Pretreatement with PKC activatior (PMA) protected taxol-induced cell death in C6-glial cells, by inhibited caspases-3 activity. On the other hand, the taxol-induced apoptosis was highly enhanced by sodium nitroprusside (SNP) and lipopolysaccharide (LPS), as NO activator. These results suggest that PMA strongly blocks the apoptotic effect of taxol, while nitric oxide has no protective effects in the process of toxol-induced apoptosis in C6-glial cells.

Effect of TRH on Phospholipase D Activity in GH3 Cell / 대한내분비학회지

BACKGROUND: GH3 cells are a well characterized and widely used model used for the in vitro study of growth hormone (GH) secretion. Thyrotropin releasing hormone (TRH) binds to receptors belonging to the family of G protein-coupled receptors, and secrets both GH & prolactin. Phospholipase D (PLD) is an enzyme that hydrolyses phosphatidylcholine to yield phosphatidic acid and choline, and plays important roles in cellular proliferation and hormonal secretion. To elucidate the pathway of the action of TRH in GH3 cells, we investigated the activities of PLC and PLD in GH3 cells treated with TRH or phorbor 12-myristate 13-acetate (PMA). METHODS: GH3 cells were labeled with [3H] myristate, followed by incubation of with 0.3% ethanol, prior to before the addition of the agonists. The total lipids were extracted from the harvested cells following treatment with the agonists. The PLD activity was assessed by measuring [3H] phosphatidylethanol from the [3H] phospholipid using thin layer chromatography. RESULTS: TRH (1 muM) stimulated the PLC activity by 44-fold over that of the control values. TRH (1 microM), mastoparan (5 muM), and PMA (500 muM) for 30 minutes increased PLD activity by 1.9, 1.5 and 2.2 fold, respectively, in comparison to the controls. The PLD activities after 15, 30, 60, 120 and 240 min treatments of TRH (1 microM) were 142%, 170%, 172%, 160% and 115%, respectively. CONCLUSION: These results suggest that TRH stimulates not only the PLC activity, but also the PLD activity in GH3 cells.