Dose and volume de-escalation of radiotherapy in head and neck cancer.

Radiotherapy plays a key role in the treatment of head and neck cancer. However, irradiation of the head and neck region is associated with high rates of acute and chronic toxicity. Technological advances have led to better visualisation of target volumes and critical structures and improved dose conformality in the treatment volume. Despite this, acute toxicity has not been substantially reduced and late toxicity has a significant impact on patients' quality of life. The greater radiosensitivity of tumours associated with the HPV and the development of new imaging techniques have encouraged research into new deintensified strategies to reduce the side effects of radiotherapy. The aim of this paper is to review the literature on the strategies of de-escalated treatment in dose and/or volume in head and neck cancer.

Oligometastatic non-small cell lung cancer: Current management.

BACKGROUND: In the past decade, major developments have improved the survival of patients with oligometastatic non-small cell lung cancer (NSCLC). About 20% - 50% of patients with NSCLC present with oligometastases at diagnosis. For this group of patients, it seems that an increase in survival would justify aggressive local therapies. The development of minimally invasive surgery and advanced radiotherapy techniques like stereotactic body radiation therapy (SBRT) makes local control possible for selected patients with metastatic NSCLC. The advantage of SBRT over surgery is that it is a non-invasive technique, with minimum side effects, and is more suitable for fragile and elderly patients, non-candidates for surgery, or patients who refuse surgery. AIM: The purpose of this review is to summarize the latest scientific evidence on the management of oligometastatic NSCLC, focusing on the role of radiotherapy. RELEVANCE FOR PATIENTS: The initial treatment recommended for patients with oligometastatic NSCLC is systemic therapy. Patients should be considered for radical treatment to both the primary tumor and oligometastases. Aggressive local therapy comprises surgery and/or definitive radiotherapy such as SRS or SBRT, and may be preceded or followed by systemic treatment. Recent clinical evidence from Phase II trials reports benefits in terms of PFS in patients with good performance status and long disease-free periods, with good response to systemic therapy, especially in EGFR wild-type tumors. Phase I and II trials have shown that radiotherapy combined with immunotherapy can improve tumor response rate and possibly overall survival. The recommendation is also to include OM patients in ongoing clinical trials.

Body size phenotypes comprehensively assess cardiometabolic risk and refine the association between obesity and gut microbiota.

OBJECTIVE: The gut microbiota associates with obesity and related disorders, but recent meta-analyses have found that this association is, at best, of small effect. We argue that such analyses are flawed by the use of body mass index (BMI) as sole proxy for disease, and explore a classification method that distinguishes the cardiometabolic health status of individuals to look for more comprehensive associations between gut microbes and health. DESIGN: We analyzed a 441 community-dwelling cohort on which we obtained demographic and health information, anthropometry and blood biochemistry data that served to categorize participants according to BMI, cardiometabolic health status and body size phenotypes. In addition, the participants donated fecal samples from which we performed 16S rRNA gene sequencing to analyze the gut microbiota. RESULTS: We observed that health-related variables deteriorate with increased BMI, and that there are further discrepancies within a given BMI category when distinguishing cardiometabolically healthy and unhealthy individuals. Regarding the gut microbiota, both obesity and cardiovascular disease associate with reductions in α-diversity; having lean, healthy individuals the most diverse microbiotas. Moreover, the association between the gut microbiota and health stems from particular consortia of microbes; the prevalence of consortia involving pathobionts and Lachnospiraceae are increased in obese and cardiometabolically abnormal subjects, whereas consortia including Akkermansia muciniphila and Methanobrevibacter, Oscillospira and Dialister have higher prevalence in cardiometabolically healthy and normoweight participants. CONCLUSIONS: The incorporation of cardiometabolic data allows a refined identification of dissimilarities in the gut microbiota; within a given BMI category, marker taxa associated with obesity and cardiometabolic disease are exacerbated in individuals with abnormal health status. Our results highlight the importance of the detailed assessment and classification of individuals that should be carried out prior to the evaluation of obesity treatments targeting the gut microbiota.

Cdc42p controls yeast-cell shape and virulence of Paracoccidioides brasiliensis.

Paracoccidioides brasiliensis is characterized by a multiple budding phenotype and a polymorphic cell growth, leading to the formation of cells with extreme variations in shape and size. Since Cdc42 is a pivotal molecule in establishing and maintaining polarized growth for diverse cell types, as well as during pathogenesis of certain fungi, we evaluated its role during cell growth and virulence of the yeast-form of P. brasiliensis. We used antisense technology to knock-down PbCDC42's expression in P. brasiliensis yeast cells, promoting a decrease in cell size and more homogenous cell growth, altering the typical polymorphism of wild-type cells. Reduced expression levels also lead to increased phagocytosis and decreased virulence in a mouse model of infection. We provide genetic evidences underlying Pbcdc42p as an important protein during host-pathogen interaction and the relevance of the polymorphic nature and cell size in the pathogenesis of P. brasiliensis.

Differences in cardiovascular mortality in smokers, past-smokers and non-smokers: findings from the FRENA registry.

BACKGROUND: The influence of smoking on outcome in patients with coronary artery disease (CAD) is controversial. Even less is known about its influence in patients with cerebrovascular (CVD), or peripheral artery (PAD) disease. PATIENTS AND METHODS: FRENA is an ongoing, observational registry of consecutive outpatients with symptomatic CAD, CVD, or PAD. We reviewed their cardiovascular mortality according to smoking status. RESULTS: As of May 2008, 2501 patients had been enrolled in FRENA. Of these, 439 (18%) were current smokers, 1086 (43%) past-smokers, 976 (39%) had never smoked. Current- and past-smokers were 10 years younger, more often males, and more likely to have chronic lung disease, but had diabetes, hypertension, heart failure, or renal insufficiency less often than non-smokers. Over a mean follow-up of 14 months, 123 patients died (cardiovascular death, 68). On univariate analysis, current smokers had a significantly lower rate of cardiovascular death: 1.1 (95% CI: 0.4-2.4) per 100 patient-years in current smokers; 1.9 (95% CI: 1.2-2.8) in past-smokers; 3.5 (95% CI: 2.5-4.7) in non-smokers, with no differences between patients with CAD, CVD or PAD. Mean age at cardiovascular death was 82+/-6.4; 70+/-9.9 and 67+/-15 years, respectively. On multivariate analysis, smoking status was not independently associated with a lower risk for cardiovascular death. CONCLUSIONS: Current and past-smokers with CAD, CVD or PAD had a less than half cardiovascular mortality than those who never smoked, but this may be explained by the confounding effect of additional variables. They died over 10 years younger than non-smokers.

Towards a molecular genetic system for the pathogenic fungus Paracoccidioides brasiliensis.

We herein report the development of a molecular toolbox for the dimorphic fungus Paracoccidioides brasiliensis, specifically a more efficient transformation and a gene expression system. We evaluated several parameters that influence Agrobacterium tumefaciens-mediated transformation (ATMT), such as co-cultivation conditions and host cell susceptibility. Our results show that cellular recovery and air drying of A. tumefaciens:P. brasiliensis mixtures are essential for ATMT. Overall, our data indicate a transformation efficiency of 78+/-9 transformants/co-cultivation (5+/-1 transformants/10(6) target cells). P. brasiliensis GFP-expressing isolates were also constructed by insertion of the GFP gene under the control of several fungal promoters. RT-PCR, epifluorescence microscopy and flow cytometry analysis revealed Gfp visualization for all studied promoters but without significant differences in fluorescence and gene expression levels. Moreover, we present evidence for the occurrence of random single gene copy integration per haploid nuclei and the generation of homokaryon progeny, relevant for the future use in targeted mutagenesis and linking mutations to phenotypes.

Genome size and ploidy of Paracoccidioides brasiliensis reveals a haploid DNA content: flow cytometry and GP43 sequence analysis.

The aim of this study was to evaluate genome size and ploidy of the dimorphic pathogenic fungus Paracoccidioides brasiliensis. The cell cycle analysis of 10 P. brasiliensis isolates by flow cytometry (FCM) revealed a genome size ranging from 26.3+/-0.1Mb (26.9+/-0.1fg) to 35.5+/-0.2Mb (36.3+/-0.2fg) per uninucleated yeast cell. The DNA content of conidia from P. brasiliensis ATCC 60855-30.2+/-0.8Mb (30.9+/-0.8fg) -showed no significant differences with the yeast form, possibly excluding the occurrence of ploidy shift during morphogenesis. The ploidy of several P. brasiliensis isolates was assessed by comparing genome sizing by FCM with the previously described average haploid size obtained from electrophoretic karyotyping. The analysis of intra-individual variability of a highly polymorphic P. brasiliensis gene, GP43, indicated that only one allele seems to be present. Overall, the results showed that all analysed isolates presented a haploid, or at least aneuploid, DNA content and no association was detected between genome size/ploidy and the clinical-epidemiological features of the studied isolates. This work provides new knowledge on P. brasiliensis genetics/genomics, important for future research in basic cellular/molecular mechanisms and for the development/design of molecular techniques in this fungus.

New insights into the cell cycle profile of Paracoccidioides brasiliensis.

The present work focuses on the analysis of cell cycle progression of Paracoccidioides brasiliensis yeast cells under different environmental conditions. We optimized a flow cytometric technique for cell cycle profile analysis based on high resolution measurements of nuclear DNA. Exponentially growing cells in poor-defined or rich-complex nutritional environments showed an increased percentage of daughter cells in accordance with the fungus' multiple budding and high growth rate. During the stationary growth-phase cell cycle progression in rich-complex medium was characterized by an accumulation of cells with higher DNA content or pseudohyphae-like structures, whereas in poor-defined medium arrested cells mainly displayed two DNA contents. Furthermore, the fungicide benomyl induced an arrest of the cell cycle with accumulation of cells presenting high and varying DNA contents, consistent with this fungus' unique pattern of cellular division. Altogether, our findings seem to indicate that P. brasiliensis may possess alternative control mechanisms during cell growth to manage multiple budding and its multinucleate nature.

Phylogeographical insights into the origins of the Squalius alburnoides complex via multiple hybridization events.

The origin, the phylogeographical structure and divergence times of hybridrogenetic Squalius alburnoides complex were analysed based on the complete mitochondrial cytochrome b gene (1140 pb). The molecular phylogenetic analyses suggest that the S. alburnoides complex has at least five asexual lineages of independent origin. The events that produced this ancestral hybridization took place over a long period of time. There have been multiple hybridization events throughout time, beginning in the upper Pliocene and probably continuing into the present. Increased humidity caused by climate changes in the Pliocene, along with tectonic lifting and vasculation of the Iberian Peninsula, led to the formation of current river drainages which, in turn, contributed to these hybridization events. We postulate that the Northwestern (Mondego and Douro) and the Southwest (Quarteira) drainages of the Iberian Peninsula delimited the border of the maternal ancestral distribution and that vicariant events led to the disappearance of the maternal ancestor in these regions, leaving today only the hybrid species. Two hypotheses have been suggested to explain the similarities between the mtDNA diversity observed in S. alburnoides and its maternal ancestor (S. pyrenaicus). The first hypothesizes that mtDNA similarity results from the recent extinction of the paternal ancestor, while the other postulates that: 'reconstituted non hybrid males' assumed the place of the extinct bisexual paternal ancestor and produced new hybridizations with S. pyrenaicus females.

Haplotype diversity and phylogenetic relationships among the Iberian barbels (Barbus, Cyprinidae) reveal two evolutionary lineages.

The phylogenetic relationships and haplotype diversity of all Iberian barbels were examined by analyzing the complete mitochondrial cytochrome b gene sequence (1141 bp) of 72 specimens from 59 Iberian localities. Phylogenetic findings demonstrated a clear distinction between two mitochondrial lineages and confirmed the existence of two previously considered subgenera: Barbus and Luciobarbus: The first subgenus, Barbus, is represented on the Iberian Peninsula by Barbus haasi and Barbus meridionalis. The second subgenus, Luciobarbus, includes the remaining endemic Iberian species: Barbus comizo, Barbus bocagei, Barbus microcephalus, Barbus sclateri, Barbus guiraonis, and Barbus graellsii. Mean haplotype divergence between these subgenera was 10.40%, providing evidence of a clear subdivision within the Iberian barbels. Our results conflict with those reported in a recent study, based on 307 cytochrome b base pairs, that failed to identify any division within the genus Barbus in the Iberian Peninsula. The inclusion of nine further species belonging to this genus (used as outgroups) allowed us to establish a closer relationship of the Iberian species of the subgenus Barbus with other European taxa than with the Iberian Luciobarbus, which was found to cluster with North African, Caucasian, and Greek species. At the population level, no biogeographic structure was shown by specimens of each species (only 5.98% of the variation was attributable to differences among populations of each species). Given the discrete amount of divergence found among the Luciobarbus species, the formation of current hydrographic basins during the Plio-Pleistocene seems to have played a major role in their isolation and evolution.

Nuclear and mitochondrial data reveal high genetic divergence among Atlantic and Mediterranean populations of the Iberian killifish Aphanius iberus (Teleostei: Cyprinodontidae).

The molecular divergence and phylogenetic relationships of the Iberian populations of Aphanius iberus were established using allozymes and the complete cytochrome b gene sequence. Congruent results were found with both nuclear and mitochondrial molecular markers. The Mediterranean and Atlantic populations are clearly differentiated into two independent lineages. Their high molecular divergence suggests an early isolation, and the absence of gene flow among the populations indicates their independent evolution. The nuclear and mitochondrial data reveal monophyletic clustering of the two geographical lineages, but provide weak support for the population relationships. However, the mitochondrial results differentiated the Villena population as a distinct mitochondrial unit within the Mediterranean group. Geographically broad studies across the distribution range of A. iberus have helped to elucidate the patterns of diversification of this species. The genetic divergence found between the Atlantic and the Mediterranean populations is of the same order as those found among recognized species of cyprinodontids. The identification of two discrete evolutionary lineages has important implications for the conservation of this species, since its recovery requires the recognition and preservation of natural diversity. The Mediterranean and Atlantic lineages should be managed separately to avoid loss of their genetic identity, and the genetic uniqueness of the populations should be preserved by using wild stocks as the source of genetic diversity in captive breeding programmes.

Antithrombotic potential of olive oil administration in rabbits with elevated cholesterol.

Olive oil is the main source of dietary fatty acids in the Mediterranean region. The objective of this study was to evaluate the effect of dietary supplementation with virgin olive oil in an experimental model with rabbits fed an atherogenic diet (saturated fat 48% of total fat). Four different groups of 10 animals each were studied: (1) normolipemic diet (NLD), (2) atherogenic diet or saturated fatty acid-enriched diet (SFAED), (3) NLD with 15% olive oil (NLD+OLIV), and (4) SFAED with 15% virgin olive oil (SFAED+OLIV). The animals were fed the experimental diets for 6 weeks, after which we determined serum lipid profile (total cholesterol, HDL-cholesterol, and triglycerides), platelet aggregation, platelet thromboxane B(2), aortic prostacyclin, and platelet and vascular lipid peroxidation. Scanning electron microscopic images of the vascular endothelium were studied, as were morphometric parameters in the arterial wall and thrombogenicity of the subendothelium (annular perfusion chamber). Animals fed the SFAED showed platelet hyperactivity and increased subendothelial thrombogenicity. Animals fed the SFAED+OLIV showed, compared with the SFAED group, an improved lipid profile with decreased platelet hyperactivity and subendothelial thrombogenicity and less severe morphological lesions of the endothelium and vascular wall. We conclude that supplementation of the SFAED with 15% olive oil reduced vascular thrombogenicity and platelet activation in rabbits. Although the percentage of olive oil in the diet was higher than the amount in the human diet, these results may be helpful in determining the effect of olive oil in the human thrombogenic system.

Actividad coagulante del factor VII (FVIIc) en ancianos con cardiopatía isquémica / Coagulant activity of factor VII (FVIIc) in old people with ischemic heart disease

Fundamento. La actividad coagulante del factor VII (FVIIc) aumenta con la edad y es un factor de riesgo en el sujeto de mediana edad, pero no se sabe su protagonismo en el anciano. El objetivo de este trabajo es evaluar si la FVIIc es un factor de riesgo en dicha población. Pacientes y método: Diseño: casos y controles. Formaron el grupo 'casos' 79 pacientes que cumplieron los siguientes criterios de inclusión: a) edad entre 65 y 85 años, y b) ingreso en el Hospital Valle de los Pedroches de Pozoblanco por infarto de miocardio y/o angina inestable en un período comprendido entre 2 años y 6 meses previos al inicio del estudio. El grupo 'control' lo formaron 81 sujetos, de similar edad, extraídos al azar de las listas del Padrón Municipal, excluyendo aquéllos con cardiopatía coronaria. La FVIIc se midió por métodos convencionales. El plasma problema se diluyó con plasma deficiente en FVIIc y se midieron los tiempos de coagulación tras añadir tromboplastina y calcio. La medición se calibró frente a un plasma 'control' y el resultado se presentó en forma de porcentaje sobre el control. Resultados: No hubo diferencias significativas entre la FVIIc entre casos (118,3 [22,2]) y controles (116,5 [24,4]; p = 0,630) en el grupo total. Al estratificar por edad se observó que, en el grupo de más de 75 años, los casos tenían una FVIIc superior a los controles (124,1 [18,2] frente a 113,3 [23,5]; p < 0,05). Al estratificar por sexos se observaron unos resultados en los varones similares al grupo global. En el análisis bivariable, en sujetos con enfermedad coronaria, la FVIIc se relacionó con el colesterol total, cLDL, apoproteína B, índice de masa corporal, HbA1c y edad. Los factores que se relacionaron con la FVIIc en el análisis multivariable fueron la glucosa basal, el índice de masa corporal y de forma negativa con el cHDL. Conclusiones: La FVIIc está elevada en la enfermedad coronaria del sujeto muy anciano, por lo que puede ser un factor de riesgo coronario significativo en este grupo de edad (AU)

Congruence between allozyme and cytochrome b gene sequence data in assessing genetic differentiation within the Iberian endemic Chondrostoma lemmingii (Pisces: cyprinidae).

To understand further the fragmentation of the hydrographical basins and the processes of divergence and speciation of freshwater fishes of the Iberian Peninsula, 10 populations of the Iberian endemic cyprinid Chondrostoma lemmingii were studied using 26 loci encoding 19 enzymes and the complete nucleotide sequence of the mitochondrial cytochrome b gene. Nuclear and mitochondrial DNA markers showed complete congruence in assessing the genetic differentiation among the samples analysed. This congruence was supported by a Mantel test in which a significant correlation (r=0.89) between Nei's genetic distances and sequence divergence (uncorrected p distances) was obtained. Diagnostic loci, Nei's genetic distances, and FST values, as well as the percentage of sequence divergence indicate that the Duero basin population accumulates the highest level of genetic differentiation. A moderate divergence was also observed among populations of the rest of the basins. Phenetic and phylogenetic relationships support the hypothesis that the differentiation process was not only due to hydrographical basin isolation but also due to an ancient endorrheism event, previous to hydrographical configuration, that could explain the marked differentiation of the Duero basin population.

[Coagulant activity of factor VII (FVIIc) in the elderly with ischemic heart disease]. / Actividad coagulante del factor VII (FVIIc) en ancianos con cardiopatía isquémica.

BACKGROUND: The coagulant activity of factor VII increases with age and is a risk factor in middle aged subjects. Its role in elderly people is still unknown. The aim of this study was to evaluate whether or not FVIIc is a risk factor in such population. STUDY DESIGN: cases and controls study. The group of cases consisted of 79 subjects fulfilling the following criteria: a) age between 65 and 85 years, and b) admission in the Valle de los Pedroches Hospital of Pozoblanco (Córdoba, Spain) due to a myocardial infarction and/or unstable angina, 2 or 6 months before their enrollment. The control group consisted of 81 subjects of similar age, chosen at random from the municipal registry, and excluding those with coronary heart disease. Factor VIIc was measured by conventional methods. Plasma samples were diluted with deficient plasma in FVIIc, and coagulation times were measured after adding thromboplastin and calcium. The measures were compared with a <> plasma and the results were presented as a percentage. RESULTS: There were no significant differences in the FVIIc between cases (118.3 [SD 22.2]) and controls (116.5 [24.4]; p = 0.630) in the total group. When classified according to their age, it was observed that within the group of more than 75 years old, cases had a higher FVIIc than controls (124.1 [18.2] vs 113.3 [23.5]; p < 0. 05). When the classification was carried out according to sex, male presented similar results than the total group. Bivariable analysis showed, in subjects with coronary diseases, that FVIIc was related to total cholesterol, cLDL, apoprotein B, body mass index, HbA1c, and age. Factors related to FVIIc in the multivariable analysis were basal glucose serum level, body mass index; cHDL was negatively related. CONCLUSIONS: FVIIc is higher in very old subjects with coronary diseases so it may be a significant coronary risk factor in this age group.

Antiplatelet effect of the anaesthetic drug propofol: influence of red blood cells and leucocytes.

1. The present study was designed to investigate the mechanism of the antiplatelet action of the anaesthetic propofol in vitro. 2. Human whole blood was incubated with different concentrations of propofol and its solvent Intralipid(R). We determined, platelet aggregometry in whole blood, platelet-enriched plasma (PRP), PRP plus red blood cells (RBC), and PRP plus leucocytes (LC); platelet production of thromboxane B2 (TxB2), ATP release by platelet dense granules, adenosine uptake by RBC, intraplatelet levels of cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP), and LC production of nitric oxide (NO). 3. Propofol-induced inhibition of platelet aggregation was greater in whole blood (IC50 80 - 136 microM) than in PRP (IC50>600 microM), except when aggregation was induced by arachidonic acid, in which case the antiaggregatory effect of the anaesthetic was similar in both media (IC50 72 - 85 microM). Inhibition of platelet aggregation correlated significantly with inhibition of TxB2 synthesis (r2=0.83). Propofol also inhibited granular ATP release; this effect was greatest in whole blood. 4. The presence of RBC or LC increased the antiaggregatory effect of propofol, mainly when collagen was used as aggregating agent. Intralipid inhibited the uptake of adenosine by RBC, however this effect probably does not contribute significantly to its antiaggregatory effect. 5. The anaesthetic potentiated the NO-cyclic GMP pathway, mainly by increasing the synthesis of NO by LC. Intralipid had no effect on the NO-cyclic GMP pathway in the LC-platelet interaction. 6. Propofol inhibited platelet aggregation in human whole blood, possibly through the sum of the effects of Intralipid on the platelet-RBC interaction and the increased synthesis of NO by LC in the platelet-LC interaction.

The effect of propofol on oxidative stress in platelets from surgical patients.

UNLABELLED: We investigated the changes in oxidative stress in platelets from surgical patients anesthetized with propofol. We studied 60 surgical patients (ASA physical status I and II) and 12 healthy volunteers. The patients were divided into three groups: anesthesia induced with an IV bolus dose of 4 mg/kg thiopental; anesthesia induced with an IV bolus dose of 2 mg/kg propofol; and total IV anesthesia (induction with propofol 2 mg/kg, infusion with propofol 10 mg/kg during the first 10 min, then 8 mg/kg for 10 min, and 6 mg/kg during the rest of the operation). Healthy volunteers were given an IV bolus dose of 10% fat emulsion (Intralipid). We measured the following variables in platelets: thiobarbituric acid reactive substances content, glutathione content, and glutathione peroxidase, reductase, and transferase activities. Thiopental did not modify any of the variables. Propofol decreased thiobarbituric acid reactive substances production by 25.7% and increased total glutathione content by 24.6%. The percentage of glutathione in oxidized form was 29.5% smaller in patients anesthetized with propofol. Glutathione peroxidase activity was 28.3% less, glutathione transferase was 44.5% more, and glutathione reductase was not significantly different. Intralipid had no effect on any of the variables. After infusion of propofol for 1 h, the effects were, in qualitative terms, the same as those seen after an initial bolus dose. In conclusion, our findings show that propofol has an antioxidant effect in humans. This effect may be beneficial in patients who have diseases in which free radicals play an important role. IMPLICATIONS: This study demonstrates that propofol inhibits cellular oxidative damage, measured in platelets from surgical patients. Neither thiopental nor the fat emulsion (Intralipid) showed any effect. Moreover, propofol increased the antioxidant defense of glutathione. This could be applied in the protection of tissues from ischemic damage.

Effect of dietary supplementation with evening primrose oil on vascular thrombogenesis in hyperlipemic rabbits.

The dietary intake of saturated fatty acids affects arteriosclerosis. We studied the effect of supplementation (15% wt/wt) of a hyperlipemic diet (1.3% cholesterol) with evening primrose oil (Oenothera biennis) in four groups of 10 rabbits each. After 6 weeks the aortic endothelium was analyzed morphologically with scanning electron microscopy, and the arterial wall was studied with morphometric techniques and cell nucleus counts. Endothelial functioning was analyzed by measuring prostacyclin synthesis, and thrombogenicity of the subendothelium was studied by perfusion in a Baumgartner annular chamber. Evening primrose oil reduced hypercholesterolemia (from 29 +/- 3 to 12 +/- 2 nmol/l), increased HDL-cholesterol (from 0.5 +/- 0.06 to 0.8 +/- 0.09 nmol/l) and doubled prostacyclin synthesis (from 2.7 +/- 2 to 6.2 +/- 0.7 ng/mg aorta) in rabbits on the hyperlipemic diet, reduced subendothelial surface occupied by platelets (from 6.9 +/- 0.4 to 4.8 +/- 0.3%), and reduced human platelet adhesion on the subendothelium (from 53.3 +/- 6% to 38 +/- 8%, respect to total occupation). Morphological analyses showed that evening primrose oil diminished endothelial lesions caused by the atherogenic diet, reducing area of the arterial wall (from 6.9 +/- 0.2 to 4.7 +/- 0.2 microm2 x 10(6)) and the degree of neointimal proliferation (from 0.6 +/- 0.02 to 0.4 +/- 0.09 microm2 x 10(6)). We conclude that in our experimental model, this dietary supplement enhanced the antithrombotic capacity of the endothelium, reduced subendothelial thrombogenicity, and diminished the extent of vascular wall lesions caused by the hyperlipemic diet.

The in vitro effects of propofol on tissular oxidative stress in the rat.

UNLABELLED: This study was designed to evaluate the in vitro effects of propofol on lipid peroxide formation and the glutathione antioxidant system in some tissues of Wistar rats (n = 8-10 per experiment). We measured thiobarbituric acid reactive substances (TBARS), and the activities of glutathione peroxidase (GSHpx), reductase (GSSGrd), and transferase (GSHtf). Propofol inhibited TBARS formation in a concentration-dependent manner. Etomidate and thiopental sodium 10(-6) to 10(-3) M had no effect. The effect of propofol was apparent immediately and was observed for up to 15-20 min after the start of TBARS formation. Propofol inhibited GSHpx activity by a maximum of 75.1%+/-8.4%, increased GSSGrd activity by a maximum of 188%+/-12.6%, and increased GSHtf activity by a maximum of 230%+/-20%. The solvent intralipid had no significant effect on any of the enzyme activities or on lipid peroxidation. We conclude that propofol not only inhibits lipid peroxidation, but also enhances the cellular antioxidant defense system. Propofol is thus able to prepare tissues against oxidative attack by boosting stores of reduced glutathione. IMPLICATIONS: This study demonstrates that the anesthetic propofol increases one of the most important mechanisms against cellular damage, the glutathione system. The study was performed in several tissues of healthy rats. This could be applied as a possible protection in surgical patients suffering from an ischemic process (cerebrovascular disease, coronary ischemia, etc.).