The prothrombotic state associated with obesity-induced hypertension is reduced by cocoa and its main flavanols.

BACKGROUND: Little is known about the effects of cocoa and its main flavanols on the prothrombotic state associated with the development of hypertension in diet-induced obesity models. PURPOSE: To evaluate the effects of cocoa powder, cocoa extract and their main flavanols on plasma biomarkers related to impaired coagulation and fibrinolysis and its association with hypertension and obesity-related metabolic disorders in rats fed a hypercaloric diet. METHODS: Male Wistar rats were randomly assigned to 7 treatment groups (n = 7): normal diet (ND); hypercaloric diet control group (HCD); HCD + cocoa powder (CO); HCD + cocoa extract (CO-EX); HCD + (-)-epicatechin (EPI); HCD + (+)-catechin (CAT); and HCD + procyanidin B2 (PB2). Blood pressure was measured using the tail-cuff method (week 7). At the end of the experimental period (week 8), rats were sacrificed and blood samples were collected immediately for coagulation and biochemical analyses. RESULTS: Oral administration of CO, CO-EX and their main flavanols significantly decreased plasma biomarkers related to impaired coagulation and fibrinolysis (vWF, FVIII, fibrinogen and PAI-1) in rats fed a hypercaloric diet. These effects were associated with decreased systolic and diastolic blood pressure, aortic oxidative stress (MDA levels) and improvement of dyslipidemia, insulin resistance and circulating markers of inflammation (TNF-α, IL-6 and CRP) compared to the HCD group. CONCLUSION: Our results showed that cocoa and its main flavanols may improve endothelial dysfunction and exert their antihypertensive effects by decreasing the prothrombotic state in rats fed a hypercaloric diet. Moreover, improvement of obesity-related metabolic disorders may also contribute to their BP-lowering effect.

Relación entre el diagnóstico clínico preoperatorio y el histopatológico posoperatorio, en pacientes con cáncer prostático localizado / Relationship between clinical preoperative diagnosis and postoperative histology in patients with localized prostate cancer

Introducción: Las variables relevantes preoperatorias con que cuenta el urólogo para una toma de decisión frente a un cáncer prostático localizado son: la edad, el tacto rectal, el antígeno prostático específico (APE) e informe histológico de la biopsia por punción con el Gleason. Además se pueden incluir otras variables como el volumen prostático, número de muestras de biopsias positivas, porcentaje de la muestra comprometida, etc. Nosotros quisimos evaluar el grado de concordancia entre el diagnóstico clínico-patológico preoperatorio con el hallazgo histológico, posoperatorio en pacientes prostatectomizados, debido a la implicancia pronóstica y en la toma de decisión que pudiese tener. Material y Método: Se estudiaron retrospectivamente 119 prostatectomías radicales entre marzo de 2004 y junio de 2009. Se consideraron: edad, tacto, antígeno prostático específico (APE) y score de Gleason. Se excluyeron pacientes con tratamiento antiandrogénico u hormonal neoadjuvante. Resultados: En el preoperatorio la mediana de edad fue de 66 años (61-68), de APE 7,35 ng/ml (5,38-11,8) y de Gleason fue de 6 (5-7). El 87,4 por ciento de los pacientes tenía un APE >4,0 ng/ml. El 54 por ciento (n= 64) tenía un estadio clínico T1c y el 46 por ciento (n= 55) un estadio T2. En el posoperatorio 23,5 por ciento (n= 28) tuvo un estadio pT2 y el 74 por ciento (n= 88) un estadio pT3. En pacientes con estadio pT2 el APE preoperatorio fue de 5,9 ng/ml (4,4-9,4), en el estadio pT3 fue de 7,9 ng/ml (5,7-12,8). El score de Gleason en pT2 fue de 5 (5-6), en el pT3 fue de 6 (5-7). No encontramos diferencia de edad en los estadios pT2 (67 años) y pT3 (68 años). Conclusiones: En el estudio histopatológico posoperatorio de pacientes con estadio clínico T1c y T2, se confirmó un estadio pT2 sólo en 23,5 por ciento, el 74 por ciento tenían un estadio pT3 (a, b). En el cáncer prostático localizado, el tacto rectal no fue útil en su correlación con el estadio histológico...

Introduction: Relevant preoperative variables in patients with localized prostate cancer are: age, digital rectal examination (DRE), prostatic specific antigen (PSA) level and Gleason score in the transrectal biopsy. Other variables include prostate volume, number of positive biopsy samples, percentage of involvement in the biopsy, etc. We evaluated the agreement between the preoperative clinico pathologic diagnosis and the postoperative histology report in patients submitted to prostatectomy. Material and method: This is a retrospective review of 119 radical prostatectomies performed between March 2004 and June 2009. We recorded age, DRE, PSA level, and Gleason score. Patients receiving anti-androgenic treatment or neoadjuvant hormonal treatment were excluded. Results: Preoperative findings: median age was 66 years (61-68), median PSA level was 7.35 ng/ml(5.38-11.8) and median Gleason score was 6 (5-7). PSA level >4 ng/ml was found in 87.4 percent of the patients. Clinical stage T1c was found in 54 percent (n=64) of the cases whereas 46 percent (n=55) were stage T2. Postoperative findings: stage pT2 was found in 23.5 percent (n=28) of the patients whereas 74 percent (n =88)were pT3 stage. In pT2 patients, preoperative PSA was 5,9 ng/ml (4.4-9.4). In pT3 patients, PSA was7.9 ng/ml (5.7-12.8). Gleason score in pT2 was 5 (5-6); in pT3 patients, Gleason score was 6 (5-7). No age difference was found between pT2 stage (67 years) and pT3 stage (68 years).Conclusions: Postoperative histology in patients with T1c and T2 stages confirmed a pT2 stage only in 23.5 percent of the cases; 74 percent of the cases were pT3 (a,b) stage. In localized prostate cancer, DRE was not useful for the correlation with pathologic staging, especially for stage pT3 cases. Preoperative Gleason score was relatively useful; we found understaging 36.2 percent of the cases and overstaging 21.8 percent of the patients. These variables should be considered in the initial evaluation of...

Influence of the fatty acid composition of lipids in chylomicron remnants derived from fish or corn oil on the lipid profile of cultured rat hepatocytes.

The aim of this work was to characterise the lipid and fatty acid composition of chylomicron remnants enriched in n-3 or n-6 polyunsaturated fatty acids (PUFA) and to investigate their influence on the fatty acid profiles of the lipids of rat hepatocytes cultured in monolayers. Chylomicrons were prepared from the lymph collected from the thoracic duct of rats given an oral dose of fish or corn oil (high in n-3 and n-6 PUFA, respectively), and remnants were prepared in vitro from such chylomicrons using rat plasma containing lipoprotein lipase. The fatty acids predominating in the oils abounded also in their respective chylomicrons and remnants, especially in triacylglycerols. Chylomicrons as well as remnants contained small amounts of phospholipids and long-chain PUFA that were minor in, or absent from, the dietary oils, evidently provided by the intestinal epithelium. The incubation of hepatocytes for 6 h, with either n-3 or n-6 PUFA-rich remnants (0.25-0.75 mM triacylglycerol) resulted in a dose-dependent increase in the amount of triacylglycerols and phospholipids in the cells, which was not affected further by increasing the incubation time to 19 h. Whereas hepatocyte triacylglycerols mostly incorporated the PUFA predominating in each remnant type, the fatty acid profile of cell phospholipids was virtually unchanged. In addition, irrespective of whether they were enriched in n-3 or n-6 PUFA, remnants promoted a relative decrease in the amount of cholesteryl esters, a minor hepatocyte lipid class poor in PUFA. The results demonstrate that the hepatocyte fatty acid profile is modulated in a lipid-class specific way by the amount and type of dietary PUFA delivered to cells in chylomicron remnants.

Major clofibrate effects on liver and plasma lipids are independent of changes in polyunsaturated fatty acid composition induced by dietary fat.

The effects of clofibrate on the content and composition of liver and plasma lipids was studied in mice fed for 4 wk on diets enriched in n-6 or n-3 polyunsaturated fatty acids (PUFA) from sunflower oil (SO) or fish oil (FO), respectively; both oils were fed at 9% of the diet (dry weight basis). Only FO was hypolipidemic. Both oil regimes led to slightly increased concentrations of phospholipids (PL) and triacylglycerols (TG) in liver as compared with a standard chow diet containing 2% fat. Clofibrate promoted hypolipidemia only in animals fed SO. Its main effect was to enlarge the liver, such growth increasing the amounts of major glycerophospholipids while depleting the TG. SO and FO consumption changed the proportion of n-6 or n-3 PUFA in liver and plasma lipids in opposite ways. After clofibrate action, the PUFA of liver PL were preserved better than in the absence of oil supplementation. However, most of the drug-induced changes (e.g., increased 18:1n-9 and 20:3n-6, decreased 22:6/20:5 ratios) occurred irrespective of lipids being rich in n-6 or n-3 PUFA. The concentration of sphingomyelin (SM), a minor liver lipid that virtually lacks PUFA, increased with the dietary oils, decreased with clofibrate, and changed its fatty acid composition in both situations. Thus, oil-increased SM had more 22:0 and 24:0 than clofibrate-decreased SM, which was significantly richer in 22:1 and 24:1.

The influence of chylomicron remnants on cholesteryl ester metabolism in cultured rat hepatocytes: comparison of the effects of particles enriched in n-3 or n-6 polyunsaturated fatty acids.

The effect of chylomicron remnants derived from fish oil (rich in n-3 polyunsaturated fatty acids) or corn oil (rich in n-6 polyunsaturated fatty acids) on the formation and hydrolysis of cholesteryl esters in cultured rat hepatocytes was investigated. Hepatocytes were incubated with or without fish or corn oil chylomicron remnants (0.25-0.75 mM triacylglycerol), and the activity of acyl-CoA:cholesterol acyltranferase (ACAT) and cholesteryl ester hydrolases in the cytosol (cCEH) and endoplasmic reticulum (erCEH), and the expression of mRNA for ACAT1, ACAT2 and cCEH, and of enzyme protein for erCEH was determined. Addition of either type of remnants to hepatocyte cultures resulted in a decreased activity of erCEH, cCEH (after 6 and 19 h incubation), and of ACAT (after 6 h only). Hepatocyte levels of mRNA encoding ACAT1 and ACAT2 were not affected by either type of chylomicron remnants after 6 h of incubation, while ACAT2 mRNA levels were down-regulated by fish oil remnants as compared with corn oil remnants, and also with control cells in the long term (19 h). In contrast, cCEH mRNA levels were down-regulated by chylomicron remnants derived from corn oil but not fish oil. The expression of erCEH protein was induced in response to the inhibitory effect of both types of remnants on the activity of the enzyme, with corn oil remnants having a significantly greater effect. These findings demonstrate that dietary polyunsaturated fatty acids when delivered to hepatocytes in chylomicron remnants regulate the activity of the enzymes governing the intracellular cholesteryl ester balance, and suggest that dietary n-3 and n-6 polyunsaturated fatty acids or a metabolite thereof have differential effects on the expression of their genes at the mRNA and post-transcriptional levels.

Polystachynes A-E, five cis-neo-clerodane diterpenoids from Salvia polystachya.

From the aerial parts of Salvia polystachya five new neo-clerodane diterpenoids, polystachynes A-E, have been isolated. The structures were established by spectroscopic methods, including the X-ray analysis of polystachynes C and D. The known clerodanes salvifaricin, linearolactone and dehydrokerlin were also isolated.

Anti-inflammatory activity of phenyl propanoids from Coreopsis mutica var. mutica.

The structures of three phenyl propanoids isolated from the aerial parts of Coreopsis mutica var. mutica were established by spectroscopic analysis as (-)-bornyl p-coumarate (1), (-)-bornyl ferulate (2), and (-)-bornyl caffeate (3). These compounds have been previously isolated from diverse sources. Their complete and assigned 1H- and 13C-NMR data together with an assessment of their anti-inflammatory activities are given.

Anti-inflammatory activity of phenyl propanoids from Coreopsis mutica var. mutica.

The structures of three phenyl propanoids isolated from the aerial parts of Coreopsis mutica var. mutica were established by spectroscopic analysis as (-)-bornyl p-coumarate, (-)-bornyl ferulate, and (-)-bornyl caffeate. These compounds have been previously isolated from diverse sources. Their complete and assigned 1H- and 13C-NMR data together with an assessment of their anti-inflammatory activities are given.