Protective effects of D-005, a lipid extract from Acrocomia crispa fruits, against ischemia/reperfusion-induced acute kidney injury in rats

BACKGROUND: Acute kidney injury (AKI) induced by renal ischemia/reperfusion (IR) is associated with enhanced production of reactive oxygen species in renal tissues. D-005, a lipid extract obtained from Acrocomia crispa fruit, has previously shown antioxidant effects. The aim of this work was to evaluate the effects of D-005 on renal IR-induced AKI in rats.METHODS: Rats were randomized into seven groups including a negative control group (vehicle) without AKI and six groups with renal IR-induced AKI as follows: a positive control (vehicle); D-005 treatment at 25, 100, 200, or 400 mg/kg; and dexamethasone at 3 mg/kg. All treatments were orally administered as single doses 1 hour before AKI induction. Biomarkers (serum creatinine, urea, and uric acid concentrations), oxidative variables, and histopathological AKI changes were evaluated in blood and kidney tissues.RESULTS: All D-005 doses protected against IR-induced AKI in rats by significantly decreasing biomarkers and histopathological AKI changes as assessed by reduced serum concentrations of creatinine, urea, and uric acid. In addition, all D-005 doses decreased tubular damage, as shown by fewer detached cells and casts in the tubular lumen. D-005 reversed oxidation disturbance markers by decreasing malondialdehyde and sulfhydryl group concentrations in plasma and in kidney homogenates and by increasing kidney catalase activity. Dexamethasone, the reference substance, protected against IR-induced AKI in rats by reducing biochemical and histological variables of renal damage in a similar manner.CONCLUSION: Administration of single oral doses of D-005 markedly and significantly protected against renal IRinduced AKI, possibly due to its known antioxidant effects.

Effects of grape seed extract, vitamin C, and vitamin e on ethanol- and aspirin-induced ulcers.

Effects of GSE and vitamins C and E on aspirin- and ethanol-induced gastric ulcer and associated increases of lipid peroxidation in rats were compared. Two experiments were conducted. Rats were randomized into eight groups: a negative control and seven groups that received aspirin or ethanol for ulcer induction: one positive control (vehicle) and six with VC, VE, or GSE (25 and 250 mg/kg). Ulcer indexes and gastric levels of malondialdehyde (MDA) were quantified. VC, VE, and GSE (25 and 250 mg/kg) decreased aspirin, and ethanol-induced ulcers and MDA values compared with positive control group. The magnitude of aspirin ulcer reduction was comparable for all treatments, and MDA decrease with GSE was higher than with VC and tended to be greater, albeit none significantly, than with VE. GSE was more effective than VC and VE for lowering the ethanol ulcers, while the decrease of MDA levels with GSE was greater than with VC, but comparable to that achieved with VE. GSE protected against ethanol-induced gastric ulcers more effectively than VC or VE, while its protection against aspirin ulcers was comparable for all treatments. GSE produced the greatest reductions of gastric MDA in both models.

Spatiotemporal trafficking of HIV in human plasmacytoid dendritic cells defines a persistently IFN-α-producing and partially matured phenotype.

Plasmacytoid DCs (pDCs) are innate immune cells that are specialized to produce IFN-α and to activate adaptive immune responses. Although IFN-α inhibits HIV-1 replication in vitro, the production of IFN-α by HIV-activated pDCs in vivo may contribute more to HIV pathogenesis than to protection. We have now shown that HIV-stimulated human pDCs allow for persistent IFN-α production upon repeated stimulation, express low levels of maturation molecules, and stimulate weak T cell responses. Persistent IFN-α production by HIV-stimulated pDCs correlated with increased levels of IRF7 and was dependent upon the autocrine IFN-α/ß receptor feedback loop. Because it has been shown that early endosomal trafficking of TLR9 agonists causes strong activation of the IFN-α pathway but weak activation of the NF-κB pathway, we sought to investigate whether early endosomal trafficking of HIV, a TLR7 agonist, leads to the IFN-α-producing phenotype we observed. We demonstrated that HIV preferentially traffics to the early endosome in human pDCs and therefore skews pDCs toward a partially matured, persistently IFN-α-secreting phenotype.

Antioxidant effects of D-004, a lipid extract from the Roystonea regia fruit, on the plasma of healthy men / 亚洲男科学杂志(英文版)

The aim of this study was to conduct a randomized, double-blind and placebo-controlled study to investigate the effects of D-004, a lipid extract of the Roystonea regia fruit that prevents testosterone- and phenylepinephrine-induced prostate hyperplasia in rodents, on plasma oxidative markers in healthy men. We enrolled male volunteers (20-55 years) in good health and without lower urinary tract symptoms. Thirty-four eligible participants were randomized to placebo or D-004 (320 mg) capsules administered daily for 6 weeks. An interim check-up and a final visit were conducted after 3 and 6 weeks of therapy, respectively. Physical examinations were performed at each visit, and laboratory tests were performed at baseline and at treatment completion. Oxidative variables included plasma malondialdehyde (MDA), total hydroxyperoxides (TOH), sulphydryl (SH) groups and total antioxidant status (TAS). We assessed treatment compliance and addressed adverse experiences (AEs) at weeks 3 and 6. At week 6, with D-004, the mean reductions of plasma MDA (26.7%), TOH (18.8%) and SH groups (31.6%), and the mean increase of TAS (35.3%) were significantly different from those of placebo (P<0.001 for plasma TAS, P<0.0001 for all other comparisons). D-004 did not differ from the placebo in safety indicators. There were two withdrawals (both in the D-004 group), with one due to dyspepsia (the only AE during the trial). In conclusion, D-004 displayed antioxidant effects on plasma oxidative markers in healthy men, which was consistent with findings from laboratory experimental studies.

Síndrome metabólico y factores de riesgo asociados con el estilo de vida de adolescentes de una ciudad de Argentina, 2005 / Metabolic syndrome and risk factors associated with life style among adolescents in a city in Argentina, 2005

OBJETIVOS: Determinar la prevalencia de síndrome metabólico (SM) en adolescentes de una ciudad argentina y establecer su asociación con algunos factores de riesgo vinculados con el estilo de vida. MÉTODOS: Estudio descriptivo transversal en una muestra representativa de 532 estudiantes de enseñanza secundaria de 11 a 20 años (promedio: 15,3 años; mujeres: 60,0 por ciento) de la ciudad de Posadas, Misiones, Argentina, entre julio y octubre de 2005. Se realizaron encuestas personales y sobre hábitos alimentarios, mediciones antropométricas, pruebas de sedentarismo, mediciones de la tensión arterial y pruebas de laboratorio. Se diagnosticó SM si se presentaban tres o más de las siguientes condiciones: glucemia > 110 mg/dL, triglicéridos > 110 mg/dL, colesterol de HDL < 40 mg/dL, tensión arterial sistólica o diastólica > percentil 90 y circunferencia de la cintura > percentil 90. RESULTADOS: La prevalencia de SM fue de 4,5 por ciento; significativamente mayor en varones que en mujeres (7,5 por ciento frente a 2,5 por ciento; P = 0,006) y en el grupo de 15 a 20 años que en el de 11 a 14 años (6,3 por ciento frente a 2,5 por ciento; P = 0,037). De los adolescentes, 44,7 por ciento tenía uno o más componentes del SM. El riesgo de los adolescentes con obesidad de padecer SM fue elevado (OR = 119,73; IC95 por ciento: 27,6 a 519,41). Los hábitos alimentarios y la frecuencia de consumo de alimentos fueron similares en los estudiantes con SM y sin SM, pero los primeros consumían alimentos obesogénicos con mayor frecuencia. Del total de adolescentes de la muestra, 84,8 por ciento eran sedentarios (100 por ciento de los que tenían SM). CONCLUSIONES: En Posadas, unos 1 400 estudiantes padecerían de SM y alrededor de 13 000 tendrían al menos un componente del SM. Se necesitan programas conjuntos del Estado y la comunidad para modificar los hábitos alimentarios y aumentar la actividad física, principalmente en varones, el grupo de 15-20 años y los obesos, ...

OBJECTIVES: To determine the prevalence of metabolic syndrome among adolescents in a city in Argentina and to establish its association with certain risk factors linked to life style. METHODS: Cross-sectional study of a representative sample of 532 middle and high school students from 11-20 years of age (mean: 15.3 years; females: 60 percent) in the city of Posadas, province of Misiones, Argentina, from July-October 2005. Surveys were conducted of individuals' dietary habits, anthropometric measurements, sedentary levels, blood pressure readings, and laboratory results. Metabolic syndrome was diagnosed if three or more of the following conditions were present: fasting glucose > 110 mg/dL; triglycerides > 110 mg/dL; HDL cholesterol < 40 mg/dL; arterial systolic or diastolic pressure > 90th percentile; and waist circumference > 90th percentile. RESULTS: The prevalence of metabolic syndrome was 4.5 percent; significantly higher among males than among females (7.5 percent vs. 2.5 percent; P = 0.006) and among the 15-20 year old age group than among the 11-14 year old group (6.3 percent vs. 2.5 percent; P = 0.037). Of the adolescents, 44.7 percent had one or more components of metabolic syndrome. The risk of metabolic syndrome among obese adolescents was elevated (odds ratio = 119.73; 95 percent confidence interval: 27.6-519.41). Dietary habits and frequency of food consumption were similar among students with and without metabolic syndrome; however, the first group consumed fattening foods more frequently. Of all the adolescents in the sample, 84.8 percent were sedentary (100 percent of those with metabolic syndrome). CONCLUSIONS: In the city of Posadas, some 1 400 students suffer from metabolic syndrome and about 13 000 have at least one metabolic syndrome component. Joint efforts by the state government and the community are needed to change dietary habits and increase physical activity, mainly among boys, those 15-20 years of age, and ...

[Metabolic syndrome and risk factors associated with life style among adolescents in a city in Argentina, 2005]. / Sindrome metabólico y factores de riesgo asociados con el estilo de vida de adolescentes de una ciudad de Argentina, 2005.

OBJECTIVES: To determine the prevalence of metabolic syndrome among adolescents in a city in Argentina and to establish its association with certain risk factors linked to life style. METHODS: Cross-sectional study of a representative sample of 532 middle and high school students from 11-20 years of age (mean: 15.3 years; females: 60%) in the city of Posadas, province of Misiones, Argentina, from July-October 2005. Surveys were conducted of individuals' dietary habits, anthropometric measurements, sedentary levels, blood pressure readings, and laboratory results. Metabolic syndrome was diagnosed if three or more of the following conditions were present: fasting glucose > or = 110 mg/dL; triglycerides > or = 110 mg/dL; HDL cholesterol < or = 40 mg/dL; arterial systolic or diastolic pressure > 90th percentile; and waist circumference > 90th percentile. RESULTS: The prevalence of metabolic syndrome was 4.5%; significantly higher among males than among females (7.5% vs. 2.5%; P = 0.006) and among the 15-20 year old age group than among the 11-14 year old group (6.3% vs. 2.5%; P = 0.037). Of the adolescents, 44.7% had one or more components of metabolic syndrome. The risk of metabolic syndrome among obese adolescents was elevated (odds ratio = 119.73; 95% confidence interval: 27.6-519.41). Dietary habits and frequency of food consumption were similar among students with and without metabolic syndrome; however, the first group consumed fattening foods more frequently. Of all the adolescents in the sample, 84.8% were sedentary (100% of those with metabolic syndrome). CONCLUSIONS: In the city of Posadas, some 1 400 students suffer from metabolic syndrome and about 13 000 have at least one metabolic syndrome component. Joint efforts by the state government and the community are needed to change dietary habits and increase physical activity, mainly among boys, those 15-20 years of age, and the obese, to reverse the situation and reduce the morbidity/mortality that results from metabolic syndrome.

Ex vivo antioxidant effects of D-004, a lipid extract from Roystonea regia fruits, on rat prostate tissue / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To investigate whether oral treatment with D-004, a lipid extract of the Cuban royal palm fruit, produces antioxidant effects in the prostate tissue of normal and testosterone (T)-treated rats.</p><p><b>METHODS</b>In our first experiment, normal rats were distributed into five groups: one group treated with the vehicle and four groups treated with D-004 (100, 200, 400 or 800 mg/kg). In our second experiment, rats were randomized into five groups: a negative control group and four T-injected groups. The latter were comprised of a positive control group treated with the vehicle, and three groups treated with D-004 (200, 400 or 800 mg/kg).</p><p><b>RESULTS</b>In normal rats, D-004 (100-800 mg/kg) inhibited significantly and dose-dependently iron-initiated malondialdehyde (MDA) accumulation in prostate homogenates (35.7%-80.0%) vs the controls. D-004 (200-800 mg/kg) significantly reduced baseline MDA and carbonyl groups in prostate homogenates of normal rats to approximately 80% and 50%, respectively, and totally (100%) in T-treated rats.</p><p><b>CONCLUSION</b>Oral treatment with D-004 reduced MDA and carbonyl groups dose-dependently and markedly in normal and T-injected rats. These findings show that D-004 given at doses effective to prevent prostate hyperplasia also produces antioxidant effects in the prostate tissue.</p>

CD28 interaction with filamin-A controls lipid raft accumulation at the T-cell immunological synapse.

During physiological T-cell stimulation by antigen presenting cells (APCs), a major T-cell membrane rearrangement is known to occur leading to the organization of 'supramolecular activation clusters' at the immunological synapse. A possible role for the synapse is the generation of membrane compartments where signalling may be organized and propagated. Thus, engagement of the costimulatory molecule CD28 at the immunological synapse promotes the organization of a signalling compartment by inducing cytoskeletal changes and lipid raft accumulation. We identified the actin-binding protein Filamin-A (FLNa) as a novel molecular partner of CD28. We found that, after physiological stimulation, CD28 associated with and recruited FLNa into the immunological synapse, where FLNa organized CD28 signalling. FLNa knockdown by short interfering RNA (siRNA) inhibited CD28-mediated raft accumulation at the immunological synapse and T-cell costimulation. Together, our data indicate that CD28 binding to FLNa is required to induce the T-cell cytoskeletal rearrangements leading to recruitment of lipid microdomains and signalling mediators into the immunological synapse.

Characterization of Phytophthora infestans genes regulated during the interaction with potato.

SUMMARY Suppression Subtractive Hybridization (SSH) was used to search for genes of Phytophthora infestans that are induced during the infection of potato. To avoid having to distinguish the genes of the pathogen from the plant genes involved in defence responses and to isolate the genes involved in the early stages of interaction, mycelium of P. infestans was induced by contact with the host plant and then separated from the plant tissue. A differential cDNA library was generated by SSH that compared such induced mycelium with mycelium incubated in water. The expression of about 100 cDNA fragments from this differential cDNA library was analysed by hybridization of the arrayed PCR products with mRNA from control and induced mycelium. Twenty per cent of them showed increased transcript levels in mycelium within the first 24 h after exposure to a potato leaf. For six of these cDNA clones the elevated expression in response to the potato leaf could be proven by RNA gel blot analysis. Five of these cDNA clones have predicted amino acid sequence homologies to entries in the databases, including an amino acid transporter, a sucrose transporter, a spliceosome-associated factor, an ABC transporter, and a cell division control protein. We showed that the genes corresponding to these six cDNA clones are differentially regulated during their life. Reliable gene expression analysis of Phytophthora in infected leaf tissue is not possible until c. 48 h post-infection, but for two of the genes we identified, induction during in planta growth was detectable by RNA gel blot analysis. Therefore the SSH library that we have created provides a basis for the identification of P. infestans genes that are up-regulated during the interaction with the plant, which could be important for pathogenicity.