TOPAS simulation of photoneutrons in radiotherapy: accuracy and speed with variance reduction.

Objective. We provide optimal particle split numbers for speeding up TOPAS Monte Carlo simulations of linear accelerator (linac) treatment heads while maintaining accuracy. In addition, we provide a new TOPAS physics module for simulating photoneutron production and transport.Approach.TOPAS simulation of a Siemens Oncor linac was used to determine the optimal number of splits for directional bremsstrahlung splitting as a function of the field size for 6 MV and 18 MV x-ray beams. The linac simulation was validated against published data of lateral dose profiles and percentage depth-dose curves (PDD) for the largest square field (40 cm side). In separate simulations, neutron particle split and the custom TOPAS physics module was used to generate and transport photoneutrons, called 'TsPhotoNeutron'. Verification of accuracy was performed by comparing simulations with published measurements of: (1) neutron yields as a function of beam energy for thick targets of Al, Cu, Ta, W, Pb and concrete; and (2) photoneutron energy spectrum at 40 cm laterally from the isocenter of the Oncor linac from an 18 MV beam with closed jaws and MLC.Main results.The optimal number of splits obtained for directional bremsstrahlung splitting enhanced the computational efficiency by two orders of magnitude. The efficiency decreased with increasing beam energy and field size. Calculated lateral profiles in the central region agreed within 1 mm/2% from measured data, PDD curves within 1 mm/1%. For the TOPAS physics module, at a split number of 146, the efficiency of computing photoneutron yields was enhanced by a factor of 27.6, whereas it improved the accuracy over existing Geant4 physics modules.Significance.This work provides simulation parameters and a new TOPAS physics module to improve the efficiency and accuracy of TOPAS simulations that involve photonuclear processes occurring in high-Zmaterials found in linac components, patient devices, and treatment rooms, as well as to explore new therapeutic modalities such as very-high energy electron therapy.

The effectiveness of a program of physical activity and diet to modify cardiovascular risk factors in patients with severe mental illness after 3-month follow-up: CAPiCOR randomized clinical trial.

BACKGROUND: The aim of this randomized clinical trial follow-up at three months was to evaluate the effectiveness of an educational intervention with a focus on diet and physical activity (PA) to change the amount of PA, body mass index (BMI) and the waist circumference (WC) in patients with severe mental illness. METHODS: We recruited 332 outpatients with severe mental disorders undergoing treatment with antipsychotic medication from Mental Healthcare Centers of Barcelona. They were randomly assigned to an intervention or a control group. The patients in the intervention group participated in a group PA and diet educational program. The blinded measurements at 0 and 3 months were: the level of PA (IPAQ questionnaire), BMI, WC, blood pressure, dietary habits (PREDIMED questionnaire), quality of life (SF-36 questionnaire) and laboratory parameters (cholesterol, triglycerides, glucose). RESULTS: The average age was 46.7 years and 55% were males. Schizophrenia had been diagnosed in 67.1% of them. At 3 months, the average weekly walking METs rose significantly in the IG 266.05 METs (95%CI: 16.86 to 515.25; P=0.036). The total MET average also rose although not significantly: 191.38 METs (95%CI: 1.38 to 381.38; P=0.086). However, the BMI decreased significantly more in the CG, by 0.26kg/m(2) (95%CI: 0.02 to 0.51; P=0.038), than in the IG. There were no significant differences in the WC. CONCLUSIONS: The short-term results suggest that the intervention increases the level of PA, but does not improve physical or laboratory parameters. TRIAL REGISTRATION: Clinicaltrials.gov NCT01729650 (effectiveness of a physical activity and diet program in patients with psychotic disorder [CAPiCOR]).

Evaluation of the Effectiveness of a Psychoeducational Intervention in Treatment-Naïve Patients with Antidepressant Medication in Primary Care: A Randomized Controlled Trial.

BACKGROUND: There is evidence supporting the effectiveness of psychoeducation (PE) in patients with symptoms of depression in primary care (PC), but very few studies have assessed this intervention in antidepressant-naïve patients. The aim of this study is to assess the effectiveness of a PE program in these patients, since the use of antidepressant (AD) medication may interfere with the effects of the intervention. METHODS: 106 participants were included, 50 from the PE program (12 weekly 1.5-hour sessions) and 56 from the control group (CG) that received the usual care. Patients were assessed at baseline and at 3, 6, and 9 months. The main outcome measures were the Beck Depression Inventory (BDI) and remission based on the BDI. The analysis was carried out on an intention-to-treat basis. RESULTS: The PE program group showed remission of symptoms of 40% (P = 0.001) posttreatment and 42% (P = 0.012) at 6 months. The analysis only showed significant differences in the BDI score posttreatment (P = 0.008; effect size Cohen's d' = 0.55). CONCLUSIONS: The PE intervention is an effective treatment in the depressive population not treated with AD medication. Before taking an AD, psychoeducational intervention should be considered.

Contenido de sodio en minutas del Programa Nacional de Alimentación Escolar, su relación con el estado nutricional y presión arterial de escolares de primero básico de Quillota, Chile / Sodium content of meals provided by the National Public Schools Feeding Program and its realtionship with nutritional status and blood pressure in children from first grade, Quillota, Chile

Chilean children attending basic schools exhibit a high prevalence of overweight and obesity, and may present hypertension associated with an excessive sodium intake. The aim of the study was to measure the sodium content of the servings provided by the National Schools Feeding Program to first grade children attending public schools in Quillota during the year 2011, compare the results with the sodium intake recommendation established by WHO, and evaluate the nutritional status and blood pressure (BP). Sodium content of servings (ICP), nutritional status (BMI) and BP (sphingomanometer) of 333 children were measured. Meals contained 3.53+1.42 g sodium per serving. 19.2% of the children were overweight and 21.3% were obese, 7 exhibited prehypertension and I presented hypertension. The study provides background data related to early sodium exposure that is useful for designing strategies towards the reduction of sodium intake in Chile in order to reduce cardiovascular risk.

Los escolares chilenos presentan alta prevalencia de sobrepeso y obesidad, y podrían presentar hipertensión arterial asociada al consumo excesivo de sodio. El objetivo del estudio fue medir el sodio de las minutas del Programa de Alimentación Escolar entregadas a primero básico en las escuelas municipalizadas de Quillota en el año 2011, comparar los resultados con la recomendación de ingesta de la OMS, evaluar el estado nutricional y la presión arterial (PA) de escolares. Se midió el contenido de sodio de las minutas (ICP), se evaluó el estado nutricional (IMC) y se midió la PA (esfigmomanómetro) de 333 escolares. Las minutas contenían 3,53+1,42 g de sodio por ración 19,2% de escolares presentaban sobrepeso y 21,3% eran obesos, 7 escolares eran pre-hipertensos y 1 hipertenso. El estudio aporta antecedentes de exposición temprana al sodio, útiles para diseñar estrategias dirigidas a disminuir el consumo de sodio en Chile como medida de reducción del riesgo cardiovascular.

[Clinical practice variation in cataract surgery]. / Variabilidad clínica en la cirugía de la catarata.

PURPOSE: Cataract surgery rates have dramatically increased in the last two decades. However, clinical practice variation in cataract surgery has not been thoroughly studied. The aim of this review is to analyze clinical practice variation, including the causes and consequences of this phenomenon. Then, its role in health care planning and health care quality is focused, emphasizing the importance of reducing it and providing several practical strategies to accomplish it. RECENT FINDINGS: The latest researches are presented in this article. They identify the development and implementation of clinical practice guidelines as the best tool to standardize care processes. CONCLUSION: Managing unwarranted or unwanted variation would improve quality of care and may lead to a significant saving in health care spending.

Hippocampal abnormalities and age in chronic schizophrenia: morphometric study across the adult lifespan.

BACKGROUND: Hippocampal abnormalities have been demonstrated in schizophrenia. It is unclear whether these abnormalities worsen with age, and whether they affect cognition and function. AIMS: To determine whether hippocampal abnormalities in chronic schizophrenia are associated with age, cognition and socio-occupational function. METHOD: Using 3 T magnetic resonance imaging we scanned 100 persons aged 19-82 years: 51 were out-patients with stable schizophrenia at least 2 years after diagnosis and 49 were healthy volunteers matched for age and gender. Automated analysis was used to determine hippocampal volume and shape. RESULTS: There were differential effects of age in the schizophrenia and control samples on total hippocampal volume (group × age interaction: F(1,95) = 6.57, P = 0.012), with steeper age-related reduction in the schizophrenia group. Three-dimensional shape analysis located the age-related deformations predominantly in the mid-body of the hippocampus. In the schizophrenia group similar patterns of morphometric abnormalities were correlated with impaired cognition and poorer socio-occupational function. CONCLUSIONS: Hippocampal abnormalities are associated with age in people with chronic schizophrenia, with a steeper decline than in healthy individuals. These abnormalities are associated with cognitive and functional deficits, suggesting that hippocampal morphometry may be a biomarker for cognitive decline in older patients with schizophrenia.

Vitreous levels of somatostatin in patients with chronic uveitic macular oedema.

PURPOSE: Intravitreal somatostatin (SST) levels are decreased in patients with diabetic macular oedema. This deficit may be involved in the pathogenesis of this condition. The aim of the present study was to determine SST concentration in the vitreous fluid of patients with chronic uveitic macular oedema (CUMO) and quiescent intraocular inflammation. METHODS: Plasma and vitreous fluid samples were obtained during vitrectomy from 11 eyes of patients with CUMO and from 42 eyes of control subjects (idiopathic epiretinal membrane, macular hole). SST concentration was measured by radioimmunoassay. STATISTICS: χ(2)-square test, Mann-Whitney U-test, Wilcoxon test, Spearman's rank correlation coefficient, and multivariant linear regression models. RESULTS: Plasma SST concentrations were similar in uveitic patients and controls (28.25 pg/ml (21.3-31) vs 28.7 pg/ml (22-29.5); P=0.869). A higher vitreous concentration of proteins was found in uveitic patients (1.59±0.38 mg/ml vs 0.73±0.32 mg/ml, P<0.0001). Vitreous SST was markedly lower in uveitic patients, both in absolute terms and after adjusting for total intravitreous protein concentration (39.37 pg/ml (6.16-172) vs 486.73 pg/ml (4.7-1833), P<0.0001; 33.1 pg/mg (3.9-215.74) vs 629.75 pg/mg (6.91-2024), P<0.0001). No correlations were found between plasma and vitreous concentration of SST in either group (ρ=0.191, P=0.57 and ρ=0.49, P=0.66). There were no correlations between vitreous SST concentration and visual acuity or macular thickness in uveitic patients (ρ=0.302, P=0.31 and ρ=0.45, P=0.13). CONCLUSIONS: Intravitreous SST is decreased in patients with CUMO and quiescent intraocular inflammation. The deficit of SST may have a role in the pathogenesis of this condition.

[Comparison of Goldmann applanation and dynamic contour tonometry measurements: effects of corneal morphometry]. / Concordancia entre la tonometría de aplanación de Goldmann y la tonometría de contorno dinámico: efectos de la morfometría corneal.

OBJECTIVES: To compare intraocular pressure (IOP) measurements made by Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT). METHODS: IOPs were measured by GAT and DCT in 63 eyes of 63 healthy subjects. A comparison was made by intraclass correlation coefficient. Passing-Bablok plot was constructed to establish the existence of systematic and/or proportional biases. Multivariate regression analysis was used to examine whether the measurements of both instruments were affected by the power of the steepest and flattest corneal axes, their orientation, age or central corneal thickness (CCT). RESULTS: The intra-class correlations (ICCs) were 0.57 (95% confidence interval (95% CI): 0.29-0.74). Mean differences were 1.68 (DCT minus GAT) (95% CI: 0.92-2.44). Passing-Bablok analysis (X=DCT, Y=GAT) revealed a systematic bias (A=-14.35, 95% CI: -24.51-[-9.14]) and a proportional bias (B=1.74, 95% CI: 1.43-2.26). Multivariate regression analysis revealed that the DCT was independent of the corneal characteristics analysed while GAT was biased by CCT (B=0.042, 95% CI: 0.002-0.082). CONCLUSIONS: While GAT was biased by corneal CCT; DCT readings were independent of corneal morphometry.

[Clinical- histological correlation in patients with dry eye]. / Correlación clínico-histológica en los pacientes con ojo seco.

AIM: It is well known that there is a lack of association between symptoms and signs in patients with dry eye disease. The purpose of this study was to assess if there was any agreement between common dry eye diagnostic tests and to compare them with impression cytology. METHODS: A total of 40 patients were enrolled in this cases-controls study. The group of cases consisted of 20 patients previously diagnosed with dry eye and the controls were 20 volunteers. The examination included: the quality of life test OSDI, break up time test (BUT), fluorescein staining, Schirmer's test and finally the study of goblet and conjunctival epithelial cells with impression cytology. The Student t and U Mann-Whitney tests were used to evaluate the results, and Spearmans Rho coefficient to assess their correlation. RESULTS: Statistical differences were observed between cases and controls Group for all tests (P<0.0001). After assessing the good correlation between BUT, fluorescein staining and Schirmer's test, we studied their association with the impression cytology. The number of isolated goblet cells showed a weak association with the majority of tests, however the grade of metaplasia showed a greater association. CONCLUSION: Impression cytology is a valuable test in the diagnosis of dry eye. Although the number of goblet cells is not a sufficient diagnostic criterion, its joint assessment with the grade of metaplasia and the other dry eye tests is useful.

Mechanisms underlying the inhibition of the cytochrome P450 system by copper ions.

Copper toxicity has been associated to the capacity of free copper ions to catalyze the production of superoxide anion and hydroxyl radical, reactive species that modify the structure and/or function of biomolecules. In addition, nonspecific Cu2+-binding to thiol enzymes, which modifies their catalytic activities, has been reported. Cytochrome P450 (CYP450) monooxygenase is a thiol protein that binds substrates in the first and limiting step of CYP450 system catalytic cycle, necessary for the metabolism of lipophilic xenobiotics. Therefore, copper ions have the potential to oxidize and bind to cysteinyl residues of this monooxygenase, altering the CYP450 system activity. To test this postulate, we studied the effect of Cu2+ alone and Cu2+/ascorbate in rat liver microsomes, to independently evaluate its nonspecific binding and its pro-oxidant effects, respectively. We assessed these effects on the absorbance spectrum of the monooxygenase, as a measure of structural damage, and p-nitroanisole O-demethylating activity of CYP450 system, as a marker of functional impairment. Data obtained indicate that Cu2+ could both oxidize and bind to some amino acid residues of the CYP450 monooxygenase but not to its heme group. The differences observed between the effects of Cu2+ and Cu2+/ascorbate show that both mechanisms are involved in the catalytic activity inhibition of CYP450 system by copper ions. The significance of these findings on the pharmacokinetics and pharmacodynamics of drugs is discussed.

Lipoprotein lipase but not hormone-sensitive lipase activities achieve normality after surgically induced weight loss in morbidly obese patients.

BACKGROUND: Although bariatric surgery is currently the most common practice for inducing weight loss in morbidly obese patients (BMI>40 kg/m2), its effect on the lipid content of adipose tissue and its lipases (lipoprotein lipase [LPL] and hormone-sensitive lipase [HSL]) are controversial. METHODS: We analyzed LPL and HSL activities and lipid content from plasma as well as subcutaneous (SAT) and visceral (VAT) adipose tissue of 34 morbidly obese patients (MO) before and after (6 and 12 months) Roux-en-Y gastric bypass surgery and compare the values with those of normal weight (control) patients. RESULTS: LPL activity was significantly higher in MO (SAT=32.9+/-1.0 vs VAT=36.4+/-3.3 mU/g tissue; p<0.001) than in control subjects (SAT=8.2+/-1.4 vs VAT=6.8+/-1.0 mU/g tissue) in both adipose depots. HSL activity had similar values in both types of tissue (SAT=32.8+/-1.6 and VAT=32.9+/-1.6 mU/g) of MO. In the control group, we found similar results but with lower values (SAT=11.9+/-1.4 vs VAT=12.1+/-1.4 mU/g tissue). Twelve months after surgery, SAT LPL activity diminished (9.8+/-1.4 mU/g tissue, p<0.001 vs morbidly obese), while HSL (46.6+/-3.7 mU/g tissue) remained high. All lipids in tissue and plasma diminished after bariatric surgery except plasma nonesterified fatty acids, which maintained higher levels than controls (16+/-3 vs 9+/-0 mg/dL; p<0.001, respectively). CONCLUSIONS: When obese patients lose weight, they lose not only part of the lipid content of the cells but also the capacity to store triacylglycerides in SAT depots.

Ghrelin and apolipoprotein AIV levels show opposite trends to leptin levels during weight loss in morbidly obese patients.

BACKGROUND: Although bariatric surgery is the most common procedure used to induce weight loss in morbidly obese patients, its effect on plasma satiety factors (leptin, ghrelin, and apolipoprotein (apo)-AIV) is controversial. The aim of this work was to analyze these parameters before and at different times after surgery. METHODS: Plasma was obtained from 34 patients before undergoing Roux-en-Y gastric bypass and during weight loss in the 12 months following surgery. RESULTS: Morbidly obese patients had significantly higher values (147%) of leptin than normal-weight (NW) persons, while their ghrelin levels were 46% less than NW. Apo-AIV levels had approximately the same value in both groups (obese and NW). During weight loss, leptin decreased by 75% and ghrelin increased by 78%. Both parameters reached values less than or near NW, respectively, at 1 year after surgery. During the first month after surgery, apo-AIV plasma levels decreased (47%) but later increased and finally returned to preoperative values. Apo-AIV levels were correlated negatively with leptin and positively with ghrelin. High-density lipoprotein (HDL) levels were positively correlated with those of ghrelin and apo-AIV. CONCLUSIONS: During weight loss, plasma leptin and ghrelin could be good markers of total fat decrease. Ghrelin could also indicate gastric mucous improvement, whereas apo-AIV could indicate the recovery of intestinal function. Changes produced in the HDL levels of morbidly obese patients during weight loss suggest a decreased risk of coronary disease.

[Quick and simple synthesis of (11)C-(+)-alpha-dihydrotetrabenazine to be used as a PET radioligand of vesicular monoamine transporters]. / Síntesis rápida y simplificada de C-(+)-alpha-dihidrotetrabenazina para su utilización como radioligando PET de los transportadores vesiculares de monoaminas.

UNLABELLED: Dihydrotetrabenazine (2-hydroxy-3-isobutyl-9,10-dimethoxy-1,3,4,6,7-hexahydro-11bH-benzo[a]-quinolizine, DTBZ) has become the ideal radioligand for the presynaptic vesicular monoamine transporter VMAT2 based on its high binding affinity and optimal lipophilicity. OBJECTIVE: To develop an automatic procedure for labelling DTBZ with carbon-11, which has been shown to be a highly effective marker for in vivo studies of neuronal losses in animal models with Parkinson's disease using positron emission tomography (PET). MATERIALS AND METHODS: We have developed a new fully automated synthesis procedure to obtain 11C-(+)DTBZ quickly and simply through labelling the precursor -(+)desmethyldihy-drotetrabenazine- at room temperature in the presence of dimethyl sulfoxide (DMSO) and potassium hydroxide (KOH), using 11CH3I as primary precursor. The final purification was carried out by solid phase extraction using commercially available cartridges and the residual solvents (DMSO and ethyl ether) were eliminated by evaporation. RESULTS: The whole procedure was automated, and after 54 syntheses, an average production of 1.94 GBq of sterile, pyrogen-free 11C-(+)DTBZ with a radiochemical purity > 99 % was obtained with 5 minutes irradiation and 6 minutes of synthesis after 11CH3I production. 11C-(+)DTBZ binding to presynaptic dopamine nerve terminals has been demonstrated by MicroPET studies in Wistar rats and M. Fascicularis monkeys. CONCLUSIONS: This new synthesis procedure is quick and simple, due to optimised techniques, which have allowed elimination of residual solvents based on their polarity for the final purification. It is also applicable to other automatic syntheses for obtaining compounds labelled by methylation reactions.

Impaired response inhibition in obsessive compulsive disorder.

OBJECTIVE: The present study investigates different three inhibitory control functions in patients with obsessive-compulsive disorder (OCD). Selective motor response inhibition was tested in a GO/NO-GO paradigm, the inhibition of a triggered motor response in a STOP paradigm and the ability to inhibit cognitive interference in a motor STROOP paradigm. METHODS: 27 patients who met DSM-IV criteria for OCD and 25 age, handedness and IQ-matched healthy control subjects were tested in the GO/NO-GO, STOP and motor STROOP tasks. RESULTS: OCD patients performed significantly worse than controls in the selective inhibition of their motor responses (GO/NO-GO) and in the inhibition of cognitive interference (STROOP), and also showed worse performance in suppressing previously triggered motor responses (STOP). CONCLUSION: Patients with OCD are impaired in motor and cognitive inhibitory mechanisms. The findings are consistent with psychobiological and neuropsychological models of OCD suggesting impairment of frontostriatal circuitries that mediate functions of inhibitory control.

Behavior of free testosterone in patients with prostate cancer on androgen deprivation therapy.

OBJECTIVES: Determination of free testosterone (FT) serum level is an efficient method to evaluate bioavailable testosterone. We analyzed the behavior of serum FT in patients with prostate cancer receiving androgen deprivation therapy (ADT) and correlated FT with total testosterone (TT). We also analyzed the efficiency of both isoforms in the evaluation of the ADT. METHODS: Serum levels of TT and FT were determined in 191 patients with prostate cancer in a cross-sectional study. A subset of 56 patients submitted only to radical prostatectomy served as control group. The remaining 135 patients with advanced prostate cancer on three-month LHRH agonist treatment comprised the study group. The median age of the population was 73 years (range, 53-86 years) and the median time on ADT was 42 months (6-198). RESULTS: A significant correlation and linear regression between TT and FT was observed (r2 0.948). The efficiency of TT and FT to discriminate patients with and without ADT was similar (AUC: 0.993 and 0.995, respectively, p > 0.05). A castration level of serum FT established at 1.7 pg/mL had a sensitivity of 85.9% and a specificity of 100%, which are similar to the sensitivity and specificity of 50 ng/dL of TT. All patients without ADT had levels of serum TT and FT above the castration level. In 19 of the 135 (14.1%) patients on ADT serum TT was above 50 ng/dL. In 12 of these 19 patients (63.2%) serum FT was below 1.7 pg/mL while in seven patients (5.2%) FT was also above the castration level. CONCLUSIONS: The castration level of FT was established at 1.7 pg/mL. Serum TT and TF correlated very well; however, they seemed to provide complementary information in the evaluation of ADT efficiency. 14.1% of the patients on ADT failed to reach the castration level of serum TT; determination of serum FT in these patients would reduce this rate to 5.2%.

Selective translocation of protein kinase c isozymes by PAF in rabbit platelets.

The action of platelet activating factor (PAF) on subcellular distribution and activity of protein kinase C (PKC) isoforms in rabbit platelets was analyzed. The results showed an increase of PKC alpha in membrane fraction, concomitantly with a decrease in cytosolic fraction after 5 min PAF treatment, indicating that a translocation of PKC alpha occurred. In addition, PKC zeta was redistributed in a "reverse" form, from the membrane to cytosolic fraction after PAF treatment. PAF induced an increase of PKC alpha activity, whereas a decrease rather than increase in PKC zeta was observed by using immunoprecipitation assays. In addition, some results indicated that PI3 kinase activation was not involved in PAF-induced PKC zeta translocation as occur in several cells and with other agonists. These actions were time- and concentration-dependent, and were inhibited by the treatment with a PAF antagonist. No translocation was observed when the platelets were incubated with lysoPAF, a PAF related compound. The redistribution of PKC isoforms take place through the activation of high specificity PAF binding sites. The pretreatment of the rabbit platelets with staurosporine, a putative inhibitor of PKC, completely blocked the PAF-evoked aggregation without affecting to PAF-evoked shape change and serotonin release. All together, these data could suggest that the specific translocation of PKC isoforms play an important role in the activation of rabbit platelets.

Usefulness of prostate-specific antigen nadir as predictor of androgen-independent progression of metastatic prostate cancer.

The objective of this study was to analyze the value of the nadir level of prostate-specific antigen (PSA) to predict androgen-independent progression (AIP) in metastatic prostate cancer patients after androgen deprivation therapy. In a group of 185 metastatic prostate cancer patients who received androgen deprivation therapy serum PSA was determined every three months until AIP occurred. Multiple regression analysis was performed to define independent clinical and PSA-related predictors of AIP. AIP was assumed to be present after two consecutive increases in serum PSA after the PSA nadir. Independent predictors of the duration of AIP-free survival (less than 12 months versus more than 12 months) were the extent of bone involvement (six or fewer hot spots versus more than six) with an odds ratio (O.R.) of 3.95, Gleason score (7 or less versus more than 7) with an O.R. of 3.47, and PSA nadir (2 microg/L or less versus more than 2 microg/L) with an O.R. of 14.63. AIP was independently predicted by the extent of bone involvement with an O.R. of 1.72, Gleason score with an O.R. of 1.74, PSA nadir with an O.R. of 3.22, and time to reach the PSA nadir (9 months or less versus more than 9 months) with an O.R. of 2.84. When patients were stratified according to these predictors, those with three good prognostic factors had a median AIP-free survival of 58 months while those with two, one or no good prognostic factors had a median AIP-free survival of 19 months, 12 months and 7 months, respectively. We conclude that the PSA nadir seems to be a good predictor of AIP in patients with metastatic prostate cancer after androgen deprivation therapy. Time to PSA nadir, extent of bone involvement and Gleason score are also independent predictors. The combination of these prognostic factors allows to stratify metastatic prostate cancer patients for the prediction of AIP.

Endothelin-1 decreases ethanolamine plasmalogen levels and evokes PAF production in brain microvessels.

Treatment of brain microvessels with Endothelin-1 evoked a decrease in ethanolamine plasmalogen levels by calcium-independent phospholipase A(2). In contrast, the diacyl molecular forms of ethanolamine phospholipids were unaffected. Evidence also shows that Endothelin type A receptors are involved. Concomitantly, PAF production mediated by CoA-independent transacylase was observed. This is the first evidence of involvement of these pathways on the Endothelin-1 mechanism of action on the blood-brain barrier.