Phytochemical uptake following human consumption of Montmorency tart cherry (L. Prunus cerasus) and influence of phenolic acids on vascular smooth muscle cells in vitro.

PURPOSE: To investigate the phytochemical uptake following human consumption of Montmorency tart cherry (L. Prunus cerasus) and influence of selected phenolic acids on vascular smooth muscle cells in vitro. METHODS: In a randomised, double-blinded, crossover design, 12 healthy males consumed either 30 or 60 mL of Montmorency tart cherry concentrate. Following analysis of the juice composition, venous blood samples were taken before and 1, 2, 3, 5 and 8 h post-consumption of the beverage. In addition to examining some aspects of the concentrate contents, plasma concentrations of protocatechuic acid (PCA), vanillic acid (VA) and chlorogenic (CHL) acid were analysed by reversed-phase high-performance liquid chromatography (HPLC) with diode array for quantitation and mass spectrometry detection (LCMS) for qualitative purposes. Vascular smooth muscle cell migration and proliferation were also assessed in vitro. RESULTS: Both the 30 and 60 mL doses of Montmorency cherry concentrate contained high amounts of total phenolics (71.37 ± 0.11; 142.73 ± 0.22 mg/L) and total anthocyanins (62.47 ± 0.31; 31.24 ± 0.16 mg/L), as well as large quantities of CHL (0.205 ± 0.24; 0.410 ± 0.48 mg/L) and VA (0.253 ± 0.84; 0.506 ± 1.68 mg/L). HPLC/LCMS identified two dihydroxybenzoic acids (PCA and VA) in plasma following MC concentrate consumption. Both compounds were most abundant 1-2 h post-initial ingestion with traces detectable at 8 h post-ingestion. Cell migration was significantly influenced by the combination of PCA and VA, but not in isolation. There was no effect of the compounds on cell proliferation. CONCLUSIONS: These data show new information that phenolic compounds thought to exert vasoactive properties are bioavailable in vivo following MC consumption and subsequently can influence cell behaviour. These data may be useful for the design and interpretation of intervention studies investigating the health effects of Montmorency cherries.

Occupational exposure to endocrine disruptors and lymphoma risk in a multi-centric European study.

BACKGROUND: Incidence rates of lymphoma are usually higher in men than in women, and oestrogens may protect against lymphoma. METHODS: We evaluated occupational exposure to endocrine disrupting chemicals (EDCs) among 2457 controls and 2178 incident lymphoma cases and subtypes from the European Epilymph study. RESULTS: Over 30 years of exposure to EDCs compared to no exposure was associated with a 24% increased risk of mature B-cell neoplasms (P-trend=0.02). Associations were observed among men, but not women. CONCLUSIONS: Prolonged occupational exposure to endocrine disruptors seems to be moderately associated with some lymphoma subtypes.

Postmenopausal hormone therapy and non-Hodgkin lymphoma: a pooled analysis of InterLymph case-control studies.

BACKGROUND: Non-Hodgkin lymphoma (NHL) subtypes, diffuse large B-cell (DLBCL) and follicular lymphoma (FL) have different sex ratios and are diagnosed at ages over 60 years; DLBCL is more common in men and diagnosed at older ages than FL, which occurs more among women. This analysis of postmenopausal women examines the relationship between postmenopausal hormone therapy and NHL. DESIGN: Self-reported use of postmenopausal hormone therapy from 2094 postmenopausal women with NHL and 2731 without were pooled across nine case-control studies (1983-2005) from North America, Europe and Japan. Study-specific odds ratios (OR) and 95% confidence intervals (CI) estimated using logistic regression were pooled using random-effects meta-analyses. RESULTS: Postmenopausal women who used hormone therapy were at decreased risk of NHL (pooled OR = 0.79, 95% CI 0.69-0.90). Risks were reduced when the age of starting was 50 years or older. There was no clear trend with number of years of use. Current users were at decreased risk while those stopping over 2 years before diagnosis were not. Having a hysterectomy or not did not affect the risk. Favourable effects were present for DLBCL (pooled OR = 0.66, 95% CI 0.54-0.80) and FL (pooled OR = 0.82, 95% CI 0.66-1.01). CONCLUSION: Postmenopausal hormone therapy, particularly used close to menopause, is associated with a decreased risk of NHL.

Menstrual and reproductive factors, and hormonal contraception use: associations with non-Hodgkin lymphoma in a pooled analysis of InterLymph case-control studies.

BACKGROUND: The two most common forms of non-Hodgkin lymphoma (NHL) exhibit different sex ratios: diffuse large B-cell lymphoma (DLBCL) occurs more frequently in men and follicular lymphoma (FL) more frequently in women. Looking among women alone, this pooled analysis explores the relationship between reproductive histories and these cancers. MATERIALS AND METHODS: Self-reported reproductive histories from 4263 women with NHL and 5971 women without NHL were pooled across 18 case-control studies (1983-2005) from North America, Europe and Japan. Study-specific odd ratios (ORs) and confidence intervals (CIs) were estimated using logistic regression and pooled using random-effects meta-analyses. RESULTS: Associations with reproductive factors were found for FL rather than NHL overall and DLBCL. In particular, the risk of FL decreased with increasing number of pregnancies (pooled OR(trend) = 0.88, 95% CI 0.81-0.96). FL was associated with hormonal contraception (pooled OR = 1.30, 95% CI 1.04-1.63), and risks were increased when use started after the age of 21, was used for <5 years or stopped for >20 years before diagnosis. DLBCL, on the other hand, was not associated with hormonal contraception (pooled OR = 0.87, 95% CI 0.65-1.16). CONCLUSIONS: Hormonal contraception is associated with an increased risk of FL but not of DLBCL or NHL overall.

Bayesian algorithm implementation in a real time exposure assessment model on benzene with calculation of associated cancer risks.

The objective of the current study was the development of a reliable modeling platform to calculate in real time the personal exposure and the associated health risk for filling station employees evaluating current environmental parameters (traffic, meteorological and amount of fuel traded) determined by the appropriate sensor network. A set of Artificial Neural Networks (ANNs) was developed to predict benzene exposure pattern for the filling station employees. Furthermore, a Physiology Based Pharmaco-Kinetic (PBPK) risk assessment model was developed in order to calculate the lifetime probability distribution of leukemia to the employees, fed by data obtained by the ANN model. Bayesian algorithm was involved in crucial points of both model sub compartments. The application was evaluated in two filling stations (one urban and one rural). Among several algorithms available for the development of the ANN exposure model, Bayesian regularization provided the best results and seemed to be a promising technique for prediction of the exposure pattern of that occupational population group. On assessing the estimated leukemia risk under the scope of providing a distribution curve based on the exposure levels and the different susceptibility of the population, the Bayesian algorithm was a prerequisite of the Monte Carlo approach, which is integrated in the PBPK-based risk model. In conclusion, the modeling system described herein is capable of exploiting the information collected by the environmental sensors in order to estimate in real time the personal exposure and the resulting health risk for employees of gasoline filling stations.

Effects of Montmorency tart cherry (Prunus Cerasus L.) consumption on vascular function in men with early hypertension.

BACKGROUND: Tart cherries contain numerous polyphenolic compounds that could potentially improve endothelial function and reduce cardiovascular disease risk. OBJECTIVE: We sought to examine the acute effects of Montmorency tart cherry (MC) juice on vascular function in subjects with early hypertension. DESIGN: A placebo-controlled, blinded, crossover, randomized Latin square design study with a washout period of ≥14 d was conducted. Fifteen men with early hypertension [systolic blood pressure (SBP) ≥130 mm Hg, diastolic blood pressure ≥80 mm Hg, or both] received either a 60-mL dose of MC concentrate or placebo. Microvascular reactivity (laser Doppler imaging with iontophoresis), arterial stiffness (pulse wave velocity and analysis), blood pressure, and phenolic acid absorption were assessed at baseline and at 1, 2, 3, 5, and 8 h postconsumption. RESULTS: MC consumption significantly lowered SBP (P < 0.05) over a period of 3 h, with peak reductions of mean ± SEM 7 ± 3 mm Hg 2 h after MC consumption relative to the placebo. Improvements in cardiovascular disease risk factors were closely linked to increases in circulating protocatechuic and vanillic acid at 1-2 h. CONCLUSIONS: MC intake acutely reduces SBP in men with early hypertension. These benefits may be mechanistically linked to the actions of circulating phenolic acids. This study provides information on a new application of MCs in health maintenance, particularly in positively modulating SBP. This trial was registered at clinicaltrials.gov as NCT02234648.

The distribution of ventilation-perfusion ratios in the lungs of a dysmature foal.

The distribution of ventilation-perfusion (VA/Q) ratios, before and after 100 per cent oxygen, was studied in an induced-premature foal at 4 h and again at eleven days of age, using the multiple inert gas elimination technique. The major finding was an absence of low VA/Q ratios when breathing air, indicating that low PaO2 in the neonatal period was totally attributable to the right-to-left shunt. At 4 h of age the PaO2 was 5.48 kPa and the right-to-left shunt represented 33.4 per cent of the cardiac output. At eleven days of age the PaO2 was 9.76 kPa and right-to-left shunt was 10.1 per cent of cardiac output. At both ages there was a separate high mode where ventilation was greatly in excess of blood flow but at neither age were units with low VA/Q ratios present. Oxygen breathing for 40 mins did not increase the right-to-left shunt, but at eleven days right-to-left shunt decreased when 100 per cent oxygen was administered.

Phase 2 trial of carboplatin, weekly paclitaxel, and biweekly bevacizumab in patients with unresectable stage IV melanoma: a North Central Cancer Treatment Group study, N047A.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in the growth and metastatic progression of melanoma. Exposure of melanoma cells to chemotherapy induces VEGF overproduction, which in turn may allow melanoma cells to evade cell death and become chemotherapy resistant. Therefore, in patients with metastatic melanoma, the combination of chemotherapy with an agent that specifically targets VEGF might be able to control tumor growth and progression more effectively than chemotherapy alone. METHODS: A 2-stage phase 2 clinical trial was conducted in patients with unresectable stage IV (metastatic) melanoma to assess antitumor activity and the toxicity profile of the combination of carboplatin (area under the curve 6 iv on Day 1 of a 28-day cycle), paclitaxel (80 mg/m2 iv on Days 1, 8, and 15), and bevacizumab (10 mg/kg iv on Days 1 and 15). Treatment was continued until progression or intolerable toxicity. RESULTS: Fifty-three patients (62.3% male) were enrolled. Nine (17%) patients achieved partial remission, and another 30 (57%) achieved stable disease for at least 8 weeks. Median progression-free survival and median overall survival were 6 months and 12 months, respectively. One patient died after 8 treatment cycles from intracranial hemorrhage into undiagnosed brain metastases. The most common severe (grade>or=3) toxicities were neutropenia (53%), thrombocytopenia (11%), hypertension (9%), and anemia (8%). CONCLUSIONS: This combination of carboplatin, paclitaxel, and bevacizumab appears to be moderately well tolerated and clinically beneficial in patients with metastatic melanoma. Further study of this combination is warranted.

Effects of organic solvents on immobilized lipase in pectin microspheres.

Lipase from Brevibacillus agri 52 was found stable up to 90% diethylenglycol (DEG), glycerol (GLY), and 1,2 propanediol (1,2 PRO) at 37 degrees C for 1 h and the stability was reduced only approximately 20% after 12 h incubation, but in 40% dimethylsulfoxide (DMSO), lipase activity was stable only for 1 h. Inhibition of the biocatalysts with dimethylformamide (DMF) was detected at 20% solvent concentration. In water immiscible systems, the stability of lipase in n-hexane, n-tetradecane and n-heptane resembles the water activity, but in the presence of isobutanol, 1-hexanol, and butylbutirate, the stability was significantly reduced. Lipase 52 precipitates in the presence of 50% acetone or ethanol/water mixtures, but enzymatic activity was partially recovered by adding 20% GLY, DEG, 1,2 PRO, or DMSO to the reaction mixture. Furthermore, by increasing DEG in 70% DMF/DEG mixtures, the lipase activity was protected. Encapsulation of lipase in pectin gels cross-linked with calcium ions brings three to four times more enzymatic activity in 70% water miscible organic solvents compared to aqueous systems.

The remarkable effect of oxygen on the N2 selectivity of water catalytic denitrification by hydrogen.

The selective catalytic reduction of nitrates (NO3-) in pure water toward N2 formation by the use of gaseous H2 and in the presence of O2 (air) at 1 atm total pressure and 25 degrees C has been investigated over Pd-Cu supported on various mixed metal oxides, x wt % MO(x(/gamma-Al2O3 (MO(x) = CeO2, SrO, Mn2O3, Cr2O3, Y2O3, and TiO2). It is demonstrated for the firsttime that a remarkable improvement in N2 reaction selectivity (by 80 percentage units) can be achieved when oxygen is present in the reducing feed gas stream. In particular, significantly lower reaction selectivities toward NH4+ and NO2- can be obtained, whereas the rate of NO3- conversion is not significantly affected. Moreover, it was shown thatthe same effect is obtained over the Pd-Cu-supported catalysts irrespective to the chemical composition of support and the initial concentration of nitrates in water used. The Pd-Cu clusters supported on 4.8 wt%TiO2/gamma-Al2O3 resulted in a solid with the best catalytic behavior compared with the rest of supports examined, both in the presence and in the absence of oxygen in the reducing feed gas stream. DRIFTS studies performed following catalytic reduction by H2 of NO3- in water revealed that the presence of TiO2 in the Pd-Cu/TiO2-Al2O3 system enhanced the reactivity of adsorbed bidentate nitrate species toward H2. Nitrosyl species adsorbed on the alumina and titania support surfaces are considered as active intermediate species of the selective catalytic reduction of NO3- by H2 in water. Pd-Cu/TiO2-Al2O3 appears to be the most selective catalyst ever reported in the literature for the reduction of nitrates present in pure water into N2 by a reducing gas mixture of H2/air.

The distribution of ventilation-perfusion ratios in the lungs of newborn foals.

The distributions of ventilation-perfusion ratios, and the effects of 100% oxygen administration on the distributions, were studied in 3 foals from 4h to 9 days of age, using the multiple inert gas elimination technique. The distributions were calculated from the pulmonary clearance of 6 inert gases following infusion into a peripheral vein of a solution containing the inert gases. The results from a total of 8 studies showed several consistent features. The major findings were (i) the absence of low ventilation-perfusion ratios, i.e. regions where blood flow was greatly in excess of ventilation; (ii) the presence of variable right to left shunt; (iii) a reduction in this shunt with increasing post-natal age; (iv) the presence of a separate high mode of ventilation-perfusion ratios where ventilation was greatly in excess of blood flow and; (v) the observation that breathing enriched oxygen mixtures for 40 min did not increase the right to left shunt in any foal at any age studied. These studies indicate that hypoxaemia in the neonatal foal is attributable to right to left shunt which may be intrapulmonary or intracardiac, or both, rather than overperfusion of poorly ventilated lungs.

Atrial natriuretic peptide release during sleep in patients with obstructive sleep apnoea before and during treatment with nasal continuous positive airway pressure.

1. Plasma levels of atrial natriuretic peptide (ANP) were measured in seven patients with obstructive sleep apnoea (OSA) while they were awake, during repetitive apnoea and during treatment with nasal continuous positive airway pressure (CPAP). 2. ANP levels in both pulmonary artery and peripheral venous samples were elevated during apnoeic sleep and reduced when apnoea was prevented by nasal CPAP. Mean values of pulmonary artery ANP were 116.3 +/- 17.9 pg/ml during apnoea and 64.8 +/- 15.2 pg/ml (P less than 0.05) on nasal CPAP. 3. It is concluded that there is increased ANP release during sleep in patients with OSA and that CPAP treatment normalizes ANP secretion. These findings may explain previously identified urinary abnormalities in OSA.

Home treatment of obstructive sleep apnoea with continuous positive airway pressure applied through a nose-mask.

Continuous positive airway pressure (CPAP) applied through the nose completely prevented obstructive apnoea during all night testing in 50 patients with severe obstructive apnoea. In early 1981, we began a home treatment trial of nasal CPAP. Patients were treated in hospital for 3 to 5 nights, a period in which they were trained to fit the custom made nose-mask used to provide nasal CPAP. Patients subsequently continued treatment at home. Daytime somnolence resolved within days of starting therapy, and did not recur while the nasal CPAP unit was used on a regular basis. At present, we have 35 patients who have been on therapy for periods ranging between 3 and 30 months. Although each patient has displayed a reduction of severity of the underlying sleep apnoea when tested without nasal CPAP, the majority continue to require regular nightly nasal CPAP. In a few patients, treatment with nasal CPAP appeared to help in weight control such that obstructive apnoea and snoring have resolved. Nasal CPAP is a safe, fully effective therapy for obstructive apnoea, and can be used indefinitely by the patient at home.

Long-term follow-up of women with ovarian cancer after positive second-look laparotomy.

OBJECTIVE: Previous reports indicate that cytoreduction and salvage therapy with P32 or whole abdominal radiation may improve survival in patients with positive findings at second-look laparotomy (SLL). The aim of this investigation was to determine whether these findings held true with extended follow-up and a larger patient cohort. METHODS: From 1977 (the year platinum-based chemotherapy was introduced to our institution) to 1989, 150 patients had persistent disease at SLL. Relevant clinical information was extracted through retrospective chart review. RESULTS: One hundred forty-five patients were followed until death, with a median follow-up of 15.4 years for the 5 living patients. Median actuarial survival from the time of SLL was 18 months. Tumor grade (P = 0.003) and pre- and post-SLL tumor size (P < 0.0001) were significant determinants of survival by univariate analysis. Patients with microscopic disease or those with < or =1 cm disease rendered microscopic at SLL had improved survival relative to those with < or =1 cm and macroscopic disease following SLL (P = 0.03) (median survivals of 3.3, 2.5, and 1.4 years, respectively). In contrast, median survival of those with >1 cm disease cytoreduced to microscopic disease was no different than those with macroscopic residual, even if < or =1 cm (1.3 and 1.0 years, respectively). After adjusting for tumor size, salvage treatment was not a significant predictor of survival. CONCLUSION: With long-term follow-up there was no suggestion that the type of salvage therapy (e.g., P32 or WART) influenced survival. Rather, low-grade disease and low tumor burdens following cytoreduction were associated with improved survival on multivariate analysis.

Reinserción social, capacidad funcional y supervivencia alejada al egreso de áreas críticas / Social reinsertion, functional capacity and survival far from leaving critical areas

Objetivos: 1) Establecer grado de supervivencia alejada (10 meses o más) al egreso de UTI; 2) Relacionar la mortalidad con los niveles de gravedad en la admisión (Score Mapuche) y el desarrollo de fracasos orgánicos (FO); 3) Relacionar las reinternaciones con el nivel de gravedad y la patología de base; 4) Evaluar la calidad de vida y el grado de reinserción laboral y social a través de parámetros objetivos y subjetivos; 5) Evaluar aspectos psíquicos y de relación médico-paciente referidos a la internación en UTI, según patología de base, y relacionarlos con secuelas psicofísicas posteriores y con reinternaciones; 6) Describir las características de la población fallecida al egreso de UTI. Material y métodos: Diseño prospectivo, observacional, transversal. Se incluyeron 105 pacientes asistidos en UTI y egresados vivos en 2 períodos: enero-septiembre 1991 y septiembre 1992-agosto 1993 (muestra azarizada), y pacientes nivel IV de la clasificación Mapuche y con 3 o más FO (en cualquier nivel), en iguales períodos, que egresaron vivos (muestra consecutiva). Se usaron como métodos estadísticos: media, porcentajes, desvío standar, chi cuadrado, T de Student y Test de Wilcoxon. Se registraron datos por revisión de Dbase y por encuesta personal o telefónica, referidos a supervivencia, y a las áreas psicológicas, afectiva, social, laboral, y a la capacidad funcional. Resultados y conclusiones: 1) Muestra con media de edad 60 años, 55 por ciento sexo M, el 67 por ciento internados menos de 6 días... 2) Sobrevivió el 79 por ciento,... 3) Mortalidad 21 por ciento... 4) Se reinternó el 16,8 por ciento... 5) El 31 por ciento presentó amnesia al egreso... 6) El 22 por ciento quienes trabajaban dejó de hacerlo; 7) El deterioro de las actividades cotidianas fue entre 13 y 61,4 por ciento; 8) El 14,4 por ciento presentó deterioro psíquico; 9) El 17 por ciento tuvo molestias en su internación, y el 50 por ciento de las mismas se debió a factores humanos del personal; 10) Se presentó miedo en el 24 por ciento... 11) Se halló relación entre deterioro psíquico y malas experiencias durante la internación... 12) El consumo de fármacos fue más alto al egreso; 13) Se observaron diferencias de mortalidad en pacientes de niveles I y II con menos de 3 FO; 14) El Mapuche mostró diferencias significativas entre fallecidos y sobrevivientes, no así los FO; 15) Hubo distinta mortalidad en ambos períodos, asociada a diferencias en el Mapuche (sin diferencias de edad y FO)