Characterization of the hypertriglyceridemic waist phenotype in patients with type2 diabetes mellitus in Spain: An epidemiological study. / Caracterización del fenotipo de cintura hipertrigliceridémica en pacientes con diabetes mellitus tipo2 en España: un estudio epidemiológico.

BACKGROUND AND OBJECTIVES: In patients with type2 diabetes mellitus (DM2), the presence of increased waist circumference and triglycerides is a reflection of increased visceral fat and insulin resistance. However, information about the prevalence and clinical characteristics of the hypertriglyceridemic waist (HTGW) phenotype in patients with DM2 is scarce. The aim of the present study was to analyze the prevalence and characteristics of DM2 patients with HTGW. METHODS: We analyzed 4214 patients with DM2 in this epidemiological, cross-sectional study conducted in primary care centers across Spain between 2011 and 2012. The HTGW phenotype was defined as increased waist circumference according to the International Diabetes Federation criteria for Europids (≥94cm for men and ≥80cm for women) with the presence of triglyceride levels ≥150mg/dl. We compared demographic, clinical and analytical variables according to the presence or absence of the HTGW phenotype. RESULTS: Thirty-five percent of patients presented the HTGW phenotype. Patients with the HTGW phenotype had a higher body mass index (31.14±4.88 vs. 29.2±4.82kg/m2; P<.001) and glycated hemoglobin levels (7.38±1.2% vs. 7±1.07%; P<.001). The presence of hypertension, peripheral arterial disease, cardiac insufficiency and microvascular complications were higher when compared with patients without the HTGW phenotype. Patients with the HTGW phenotype were less adherent to prescribed diet (69.8 vs. 81%; P<.001), exercise (44.6 vs. 58.2%; P<.001) and presented greater weight increase within the year prior to the study visit (29.4 vs. 22.5%; P<.001). CONCLUSIONS: The HTGW phenotype is prevalent in the Spanish DM2 population and identifies a subgroup of patients with higher cardiometabolic risk and prevalence of diabetic complications.

Effect of diet on carboxylesterase activity of tadpoles (Rhinella arenarum) exposed to chlorpyrifos.

An outdoor microcosm was performed with tadpoles (Rhinella arenarum) exposed to 125µgL-1 chlorpyrifos and fed two types of food, i.e., lettuce (Lactuca sativa) and a formulated commercial pellet. Acetylcholinesterase (AChE) and carboxylesterase (CbE) activities were measured in liver and intestine after 10 days of pesticide exposure. Non-exposed tadpoles fed lettuce had an intestinal AChE activity almost two-fold higher than that of pellet-fed tadpoles. No significant differences were observed, however, in liver AChE activity between diets. Likewise, intestinal CbE activity - measured using two substrates, i.e. 1-naphthyl acetate (1-NA) and 4-nitrophenyl valerate (4-NPV) - was higher in tadpoles fed lettuce than in those fed pellets. However, the diet-dependent response of liver CbE activity was opposite to that in the intestine. Chlorpyrifos caused a significant inhibition of both esterase activities, which was tissue- and diet-specific. The highest inhibition degree was found in the intestinal AChE and CbE activities of lettuce-fed tadpoles (42-78% of controls) compared with pellet-fed tadpoles (<60%). Although chlorpyrifos significantly inhibited liver CbE activity of the group fed lettuce, this effect was not observed in the group fed pellets. In general, intestinal CbE activity was more sensitive to chlorpyrifos inhibition than AChE activity. This finding, together with the high levels of basal CbE activity found in the intestine, may be understood as a detoxification system able to reduce intestinal OP uptake. Moreover, the results of this study suggest that diet is a determinant factor in toxicity testing with tadpoles to assess OP toxicity, because it modulates levels of this potential detoxifying enzyme activity.

Quantitative analysis of blood cells and inflammatory factors in wounds.

OBJECTIVE: The aim of this study was to quantify blood cells and inflammatory markers, involved in the healing process, in exudates from wounds in different healing phases, to assess these markers in order to identify the inflammatory phase of the wounds. METHOD: Patients who presented with postsurgical wounds, which closed by first and second intention, and those who presented with pressure ulcers (PUs), which were closed by second intention, were included in the study. RESULTS: We examined wounds from 37 patients and collected samples from 52 wounds in the inflammatory phase, 30 in the proliferative phase and 29 in the maturation phase. The number of neutrophils and platelets in the exudate collected from wounds in the inflammatory phase was significantly higher (p<0.001), while the number of lymphocytes, was significantly lower in exudate from wounds in the inflammatory phase (p<0.001). Wound c-reactive protein (CRP) and immunoglobulin G (IgG) levels were higher in the inflammatory group (p<0.001). We found a significantly positive correlation between CRP levels and the percentage of neutrophils and monocytes (r=0.346, p=0.004; r=0.293, p=0.015), and a significantly negative correlation between CRP levels and the percentage of lymphocytes (r=-0.503, p<0.001). A stepwise logistic regression analysis was used to identify an optimal combination of these biomarkers. The optimal biomarker combinations were neutrophils + monocytes + platelets + IgG + CRP, with an area under the curve (AUC) of 0.981 [confidence interval (CI) 95%: 0.955-1.000, p<0.001] for the diagnosis of wounds in the inflammatory phase. The optimal cutpoint yielded 96.9 % sensitivity and 94.6 % specificity. The biomarker combination predicted the inflammatory phase and was superior to individual biomarkers. CONCLUSION: Our findings suggest that the combination of the markers, percentage of neutrophils and monocytes, platelets, CRP and IgG levels could be useful prognostic indicators of the inflammatory phase.

From autochthonous to allochthonous resources: seasonal shifts in food use by stream-dwelling YOY Arctic charr Salvelinus alpinus through the ice-free season.

Substantial seasonal changes in resource use associated with enhanced water-column use were revealed in stream-living YOY Arctic charr Salvelinus alpinus during the ice-free season. In July, YOY individuals showed a diet dominated by aquatic invertebrates (mainly Chironomidae larvae), but despite the small size of the fish, the abundance of terrestrial insects in their diet increased markedly from July to September (from 1·9 to 62·8%). Similarly, the frequency of surface drifting foragers, i.e. individuals feeding on allochthonous resources, increased from July to September (from 20·6 to 80%); allochthonous resources thus constituting an important energy subsidy for YOY S. alpinus during the late sub-Arctic summer.

Gait parameters in a reference sample of healthy Spanish schoolchildren: multivariate descriptive statistics and asymmetries observed in left and right cycles.

INTRODUCTION: Instrumental gait analysis is an emerging technology used increasingly to evaluate motor disorders in children. Normal reference data is necessary in order to evaluate patients, but there are few reference resources for the Spanish paediatric population. OBJECTIVE: We aim to describe the values of 16 clinically relevant gait variables in healthy Spanish schoolchildren, and identify any linear associations or left-right asymmetries. SUBJECTS AND METHODS: The values of 16 gait variables were determined in schoolchildren (n=27, aged 5-13 years) using instrumental gait analysis. We analysed asymmetries for each variable (Student's t-test for dependent samples) and calculated their confidence intervals (95% of the standardised difference in right and left means [SMD]). Values and associations between variables were represented using a heat map. RESULTS: Our project presents normal values tables for 16 variables in the gait cycle. Significant asymmetries were detected in the mean values for minimum hip flexion (SMD: 0.25 95% CI, 0.11-0.39) and peak hip abduction in swing (SMD: -1.05 95% CI: -1.71--0.27). Functional associations among gait variables are present. CONCLUSIONS: We present a reference dataset for Spanish school-aged children in which left-right asymmetries and functional associations may be observed for different variables.

The nigrostriatal system in the presymptomatic and symptomatic stages in the MPTP monkey model: a PET, histological and biochemical study.

Parkinson's disease (PD) is diagnosed when striatal dopamine (DA) loss exceeds a certain threshold and the cardinal motor features become apparent. The presymptomatic compensatory mechanisms underlying the lack of motor manifestations despite progressive striatal depletion are not well understood. Most animal models of PD involve the induction of a severe dopaminergic deficit in an acute manner, which departs from the typical, chronic evolution of PD in humans. We have used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administered to monkeys via a slow intoxication protocol to produce a more gradual development of nigral lesion. Twelve control and 38 MPTP-intoxicated monkeys were divided into four groups. The latter included monkeys who were always asymptomatic, monkeys who recovered after showing mild parkinsonian signs, and monkeys with stable, moderate and severe parkinsonism. We found a close correlation between cell loss in the substantia nigra pars compacta (SNc) and striatal dopaminergic depletion and the four motor states. There was an overall negative correlation between the degree of parkinsonism (Kurlan scale) and in vivo PET ((18)F-DOPA K(i) and (11)C-DTBZ binding potential), as well as with TH-immunoreactive cell counts in SNc, striatal dopaminergic markers (TH, DAT and VMAT2) and striatal DA concentration. This intoxication protocol permits to establish a critical threshold of SNc cell loss and dopaminergic innervation distinguishing between the asymptomatic and symptomatic parkinsonian stages. Compensatory changes in nigrostriatal dopaminergic activity occurred in the recovered and parkinsonian monkeys when DA depletion was at least 88% of control, and accordingly may be considered too late to explain compensatory mechanisms in the early asymptomatic period. Our findings suggest the need for further exploration of the role of non-striatal mechanisms in PD prior to the development of motor features.

Cervical human papillomavirus infection in Mexican women with systemic lupus erythematosus or rheumatoid arthritis.

Cervical human papillomavirus (HPV+) infection is associated with an increased risk of cervical dysplasia. Although the frequency of HPV+ in systemic lupus erythematosus (SLE) has been investigated in some races its prevalence in Hispanic women is still unknown. This cross-sectional study evaluated the prevalence of cervical HPV+ in Mexican women with SLE (n = 34) or rheumatoid arthritis (RA) (n = 43) and in healthy controls (n = 146). These women were interviewed about risk factors for sexually transmitted infections and cervical cytology analysis was performed. HPV+ viral types were identified using PCR: HPV+ was observed in 14.7% of SLE, 27.9% of RA and 30.8% of controls. High-risk HPV types were observed in 11.7% of women with SLE, 27.9% of women with RA, and in 26% of the controls. High-risk viral types 58, 35 and 18 were the most frequently identified in SLE. Two women with SLE had a high-grade squamous intraepithelial lesion and one had cervical cancer. An association was observed between methotrexate utilization, longer duration of therapy with prednisone, and HPV+ in RA or SLE. Thus, there is a high prevalence of cervical HPV infection in Mexican women with SLE or RA, and physicians must be vigilant in preventing the development of cervical dysplasia.

Effect of heavy metal exposure on blood haemoglobin concentration and methemoglobin percentage in Lumbricus terrestris.

The earthworm haemoglobin (Hb) is a large extracellular hemoprotein flowing in a closed circulatory system. In spite of the fundamental role of this respiratory pigment in earthworm physiology, little is known about its sensitivity to environmental pollutants. The aim of the present work was to investigate the possible effect of heavy metal (cadmium, copper, mercury) exposure on Hb concentration and oxidation state (methemoglobin formation) in the earthworm Lumbricus terrestris. In addition, the tissue concentration of metallothioneins, a well-known biomarker of heavy metal exposure, was determined as an indicator of metal uptake. The animals were exposed to increasing concentrations of Cd, Cu and Hg utilizing the standard acute toxicity test, "Filter paper test" for 48 h. Exposure to heavy metals (10(-5)-10(-3) M for Cd, 10(-4)-10(-3) M for Hg, and 10(-4)-10(-2) M for Cu) was found to increase haemoglobin concentration in L. terrestris, although the magnitude of such an increase was dependent on the metal. In addition, metal exposure led to the formation of methemoglobin. Compared to other known biological responses to heavy metals, such as metallothionein induction, methemoglobin increase showed a higher sensitivity and a higher percentage variation in exposed organisms, showing to be a possible suitable biomarker of exposure/effect to be included in a multi biomarker strategy in earthworm in soil monitoring assessment.

Characterization of the hypertriglyceridemic waist phenotype in patients with type 2 diabetes mellitus in Spain: an epidemiological study.

BACKGROUND AND OBJECTIVES: In patients with type 2 diabetes mellitus (DM2), the presence of increased waist circumference and triglycerides is a reflection of increased visceral fat and insulin resistance. However, information about the prevalence and clinical characteristics of the hypertriglyceridemic waist (HTGW) phenotype in patients with DM2 is scarce. The aim of the present study was to analyze the prevalence and characteristics of DM2 patients with HTGW. METHODS: We analyzed 4214 patients with DM2 in this epidemiological, cross-sectional study conducted in primary care centers across Spain between 2011 and 2012. The HTGW phenotype was defined as increased waist circumference according to the International Diabetes Federation criteria for Europids (≥ 94 cm for men and ≥ 80 cm for women) with the presence of triglyceride levels ≥ 150 mg/dL. We compared the demographic, clinical and analytical variables according to the presence or absence of the HTGW phenotype. RESULTS: Thirty-five percent of patients presented the HTGW phenotype. Patients with the HTGW phenotype had a higher body mass index (31.14 ±â€¯4.88 vs. 29.2 ±â€¯4.82 kg/m2; p < .001) and glycated hemoglobin levels (7.38 ±â€¯1.2% vs. 7 ±â€¯1.07%; p < .001). The presence of hypertension, peripheral arterial disease, cardiac insufficiency and microvascular complications were higher when compared with patients without the HTGW phenotype. Patients with the HTGW phenotype were less adherent to prescribed diet (69.8 vs. 81%; p < .001), exercise (44.6 vs. 58.2%; p < .001) and presented greater weight increase within the year prior to the study visit (29.4 vs. 22.5%; p < .001). CONCLUSIONS: The HTGW phenotype is prevalent in the Spanish DM2 population and identifies a subgroup of patients with higher cardiometabolic risk and prevalence of diabetic complications.

Olive mill wastewater-evaporation ponds long term stored: Integrated assessment of in situ bioremediation strategies based on composting and vermicomposting.

During the last two decades, the method most widely used to manage olive mill wastewater (OMW) derived from olive oil production has been its disposal in evaporation ponds. Long-term storage of OMW leads to the accumulation of toxic sediments (OMWS) rich in recalcitrant compounds with phytotoxic and antimicrobial properties, which limit their use for agronomic purpose. The aim of this study was to compare the effect of two in situ bioremediation strategies (composting and a combination of composting followed by vermicomposting) to remove the potential toxicity of the sediments derived from long-term stored OMW. The results obtained showed that the composting method assisted with the earthworms enhanced the depletion of phenolic compounds and OMWS ecotoxicity more than composting, especially during the maturation stage. Moreover, vermicomposting was more effective in the reduction of the OMWS salinity. However, a pre-composting process to the OMWS is necessary prior to vermicomposting to provide the suitable conditions for earthworms survival and activity. Furthermore, the final compost showed a phytostimulating effect. Therefore, these in situ bioremediation strategies can be considered potential tools for decontamination and recovery of long-term stored OMWS in evaporation ponds, which currently poses an unsolved environmental problem.

Evolutional patterns of articular cartilage following growth plate injury in rats.

BACKGROUND: No study to date has analyzed the damage of the articular cartilage and its relation to growth plate injury. The purpose of this study was to test whether primary injury to the growth plate contributes to secondary damage to the articular cartilage in rats. METHODS: A total of 109 two-week-old male Wistar rats were allocated to four lesional groups. In group I (controls) no surgery took place. In the remaining animals, an injury was caused in the proximal physis of the left tibia: group II, perichondrial ring injury; group III, direct injury to the growth plate; group IV, traumatic separation of the epiphysis where a Salter-Harris II-type injury was created. The results were assessed at 1 week, 6 weeks, and 6 months. A growth plate score was used. The stereological and histological changes in the articular cartilage were analyzed, and the results were subjected to statistical analysis. RESULTS: Histological studies showed discrete degenerative changes in the articular cartilage in the injured growth plate. Changes in the cell density, mean cell volume, and articular cartilage occurred in the injured growth plate. The changes appeared to be transient in groups II and III. CONCLUSIONS: Primary injury to the growth plate contributes to secondary damage to the articular cartilage in young rats. Our data -- extrapolated to the clinical view -- suggests that a Salter-Harris type II injury does not seem to have impunity to subsequent joint degeneration.

Therapeutic drug monitoring of tumour necrosis factor inhibitors in the management of chronic inflammatory diseases.

Tumour necrosis factor inhibitor therapy has drastically changed the management of chronic inflammatory diseases. Some important drawbacks that can cause loss of response during treatment with these drugs are related to their large individual variability, the disease burden and the formation of antidrug antibodies that increase its clearance. Therapeutic drug monitoring of these drugs is not yet recommended by all scientific societies, and if so, only in patients with inflammatory symptoms. Proactive therapeutic drug monitoring represents a new strategy with many potential clinical benefits, including the prevention of immunogenicity, a reduction in the need for rescue therapy and greater durability of tumour necrosis factor inhibitor treatment. The review is based on a systematic search of the literature for controlled trials, systematic reviews, experimental studies, guideline papers and cohort studies addressing the best practice in tumour necrosis factor inhibitor therapeutic drug monitoring. Although there is ample evidence supporting the use of therapeutic drug monitoring in clinical practice to achieve better outcomes, some challenges have been detected. Many studies are focused on finding solutions for the lack of standardization of analytical methods to measure tumour necrosis factor inhibitor and antidrug antibodies concentrations. Other challenges are development of effective cost-saving proactive algorithms to identify optimal drug concentrations and the research on the role of antidrug antibodies, especially in the management and prevention of loss of response. Therapeutic drug monitoring of tumour necrosis factor inhibitor offers a rational approach to the optimization of the treatment of chronic inflammatory disease. Although prospective controlled trials yield little conclusive evidence of its benefits, there is growing acceptance of its value in clinical practice.

[Proximal humeral resurfacing. Whats today indication?] / Prótesis de recubrimiento en húmero proximal: ¿Cuál es la indicación hoy en día?

INTRODUCTION: Data published in the literature about humeral resurfacing prostheses are not conclusive with good functional results but with large differences in the revision rate. The aim of our study was to evaluate the clinical and functional outcomes in patients operated at our center. MATERIAL AND METHODS: Retrospective study of 19 cases in 18 patients. Follow-up of 31 (12-61) months. Surgery was indicated in cases of primary or secondary osteoarthritis. Demographic data, Constant scale, DASH questionnaire, complications and satisfaction were analyzed. Three patients were lost to follow-up due to death unrelated to surgery. RESULTS: Mean age of 56 (25-80) years. Constant normalized of 73 (23-104) points. DASH questionnaire of 31 (7-84) points. Ninety four percent of the patients resumed their recreational activities and 81% sports activities. In seven cases, inferior conflict in the glenoid with varus implant was observed radiologically. There were five complications; a conservatively resolved capsulitis, three reinterventions due to symptomatic inferior glenoid usury and another to uncontrollable pain in a conservative way. Patients without rotator cuff lesion presented better scores on the functional questionnaires. All patients were satisfied with the symptomatic improvement over the previous situation and would be operated again if necessary. CONCLUSIONS: The functional outcomes reported are similar to those previously published and, based on them, we believe that the resurfacing prosthesis is an option to be considered in cases of primary or secondary osteoarthritis when there is no rotator cuff injury, regardless of age.

INTRODUCCIÓN: Los resultados funcionales de las prótesis de superficie en el húmero proximal son aceptables, pero con grandes diferencias en la tasa y causa de revisión según las diferentes series. El objetivo de nuestro trabajo fue analizar los resultados clínicos obtenidos en nuestro centro y tratar de definir al paciente ideal para este implante. MATERIAL Y MÉTODOS: Estudio retrospectivo de 19 casos. Seguimiento de 31 (12-61) meses. La cirugía se indicó en casos de artrosis primaria o secundaria. Se analizaron datos demográficos, escala de Constant normalizada, cuestionario DASH, complicaciones y satisfacción. Hubo tres pérdidas durante el seguimiento por fallecimiento sin relación con la cirugía. RESULTADOS: Edad media de 56 (25-80) años. La puntuación en la escala de Constant normalizada fue 73 (23-104) puntos y en el cuestionario DASH 31 (7-84) puntos. Noventa y cuatro por ciento de los pacientes retomaron sus actividades de ocio. En siete casos se objetivó radiológicamente colocación en varo del implante generando un conflicto inferior en la glena. Se produjo una capsulitis adhesiva resuelta de forma conservadora, tres reintervenciones por usura glenoidea sintomática y una por dolor incontrolable. Los pacientes sin lesión del manguito rotador presentaron mejor puntuación en los cuestionarios funcionales. Todos los pacientes refirieron estar satisfechos con la mejoría sintomática respecto a la situación previa. CONCLUSIONES: Los resultados funcionales obtenidos son similares a los publicados previamente. Creemos que la prótesis de superficie debe ser considerada una opción en los casos de artrosis primaria o secundaria sin lesión del manguito rotador, independientemente de la edad.

Pharmacokinetics and dosing requirements of digoxin in pregnant women treated for fetal supraventricular tachycardia.

BACKGROUND: The objective of this study was to characterize the pharmacokinetics (PK) of digoxin in pregnant women and its potential implications for drug dosing. METHODS: Serum digoxin concentrations (SDCs) obtained in pregnant women treated for fetal supraventricular tachycardia (SVT) was retrospectively collected. PK analysis was comparatively performed using a two-stage approach (PKS™) and a Population PK approach (NONMEM™). As clinical outcome the fetal heart rate was recorded. RESULTS: A total of 42 SDCs were obtained from 8 women in the 3rd trimester of pregnancy (mean age 33.0 years). The PK parameters estimated by both two-stage (volume of distribution (Vd) = 682.0 L, CV = 47.5%; serum clearance (CL) = 16.1 L/h, CV = 19%) and population approaches (Vd = 731.3 L, CV = 30.5%; CL = 18.7 L/h, CV = 17.8%) are very similar and show a clear trend of increasing drug disposition in the third trimester of pregnancy. An oral loading dose of 0.5 mg/8 h during 24 h followed by a maintenance regimen of 0.5 mg/12 h been recommended to start treatment. CONCLUSIONS: Despite the small population, these parameters could be used as a guide to calculate the initial dosage requirements in the third trimester of pregnancy for treating fetal SVT. In addition, maternal SDCs should be routinely monitored for dosage adjustment purposes.

Earthworm biomarkers in ecological risk assessment.

Earthworms have had a notable contribution in terrestrial ecotoxicology. They have been broadly used to assess environmental impact from metal pollution, and they are typical test organisms (e.g., Eisenia) in standardized toxicity tests. Several reviews and international workshops have stressed the need for increasing the understanding and applicability of earthworm biomarkers in the ecological risk assessment (ERA) process. This review summarizes recent available information concerning the most investigated earthworm biomarkers. In earthworms, the use of biomarkers has been focused on assessing metal pollution, and available data on biomarker responses to organic contaminants are rather limited. The potential for applying earthworm biomarkers in the standardized toxicity tests is suggested in view of their significant contribution to the risk assessment of contaminated soils (e.g., estimation of bioavailable and bioactive fraction or sublethal effects). Field studies involving earthworm biomarkers are still scarce and are summarized according to their main practical approaches in retrospective ERA: biological surveys, laboratory tests of the soil, simulated field studies, and in situ exposure bioassays. Despite the great volume of laboratory studies on earthworm biomarkers, future lines of research are suggested besides the recommendations made by others: (1) the potential and limitations of the inclusion of biomarkers in the standardized toxicity tests should be examined under a well-defined weight-of-evidence framework; (2) it is necessary to develop operating guidelines to standardize earthworm biomarker assays, an important step to apply biomarkers in a regulatory context; (3) molecular and physiological biomarkers should be directly linked to behavioral changes with significant ecological implications, an important step in considering them as ecotoxicological biomarkers; and (4) biomarkers to organic pollutants of current concern (e.g., polycyclic aromatic hydrocarbons, anti-ChE and pyrethroid insecticides, polybrominated flame retardants, etc.) need to be developed and validated in the field. Also, an increase in the knowledge of earthworm biomarkers is undoubtedly useful in assessing the effectiveness of procedures for recovering/protecting the environment (e.g., phytoremediation or agrienvironment schemes) besides its potential use in the ERA framework.

The Almadén district (Spain): anatomy of one of the world's largest Hg-contaminated sites.

We present data from an early reconnaissance survey (stream sediments, soil, and water Hg chemistry; plants and water crustaceans Hg intake) of the Almadén district (central Spain), that was carried out to establish the potential environmental hazards derived from the anomalous mercury concentrations measured in this realm. The Almadén mercury district (approximately 300 km2) can be regarded as the largest geochemical anomaly of mercury on Earth. The district includes a series of mercury mineral deposits, having in common a simple mineralogy (dominant cinnabar: HgS, and minor pyrite: FeS2). The ore deposits have been mined for more than 2000 years, and the main mine of the district (Almadén), has been active from Roman times to present day with almost no interruptions. The mercury distribution in soils of the district reveals the existence of high, and extremely high mercury values (up to 8889 microg g(-1)), whereas concentrations in stream sediments and waters reach exceptional values of up to 16,000 microg g(-1) and 11,200 ng l(-1) respectively. On the other hand, very high concentrations of methylmercury (MeHg) have been detected in calcines (up to 3100 ng g(-1)), sediments (0.32-82 ng g(-1)), and waters (0.040-30 ng l(-1)). Mercury gets incorporated to edible river crustaceans and plants. The red swamp crayfish Procambarus clarkii, has Hg concentrations of up to 9060 ng g(-1) (muscle) and 26,150 ng g(-1) (hepatopancreas). Regarding plants, the local wild asparagus (Asparagus acutifolius) yields values of up to 298 microg g(-1) Hg. Mercury also escapes to the atmosphere, and mineral deposits, together with metallurgical activities, generate strong anomalies of atmospheric Hg. The most important concentrations relate to the emissions from the Almadén metallurgical roaster, in the order of 14,000 ng Hg m(-3). Additionally, large open pit operations also contribute to the district atmospheric pool of mercury, with high concentrations above 1000 ng Hg m(-3). Thus, no system (rocks, soils, sediments, waters, atmosphere, biota) in the Almadén district is free from strong Hg contamination.

TP53 mutational pattern in Spanish and Polish non-small cell lung cancer patients: null mutations are associated with poor prognosis.

Inactivation of TP53 tumor suppressor gene is the most frequent molecular alteration in NSCLC, involving up to 60% of cases. Furthermore, TP53 mutational spectrum is related to the type of mutagen exposure, as well as racial and/or diet differences. Nearly 95% of TP53 perturbations affect codons included within exons 5-8 which encode for almost the entire DNA-binding domain. In this study we addressed the possible prognostic value of the molecular alterations identified in exons 5-8 of the TP53 gene in DNAs from 151 paraffin-embedded NSCLC sections corresponding to 59 Spanish and 92 Polish stage I-IIIA resected patients. PCR/single-strand conformation polymorphism (SSCP) analysis revealed that the occurrence of TP53 exon 5-8 mutations was 17/59 (29%) in the Spanish cohort and 17/92 (18%) in the Polish group. However, when DNA sequencing analysis was performed, these frequencies were reduced because of the presence of SSCP-false positive, intronic and silent mutations and polymorphisms. Fifteen of the 59 Spanish NSCLC tumors (25%) harbored TP53 mutations affecting exons 5-8 coding sequences, whereas only 12 of 92 Polish neoplasms (13%) contained alterations in the central hydrophobic region of p53. Our results indicate that the occurrence of TP53 mutations affecting exon 5-8 coding sequences in some European NSCLC populations may be lower than previously reported, and that the TP53 mutational patterns of these cohorts differ somewhat. The Spanish NSCLC patients contained missense mutations (9/59, 15%) and a relatively high percentage of null mutations (5/59, 8%) while the Polish patients mostly harbored missense mutations (9/92, 10%) and only one tumor contained a null type (1/92, 1%). Moreover, most TP53 missense mutations in the Spanish group were located outside the conserved regions, whereas the same mutations in the Polish group affected conserved amino acids. Furthermore, the Polish patients harbored a high percentage of G-->A transitions (most of them at non-CpG sites), while G-->T transversions were predominant in the Spanish group. Our findings suggest that there may be different racial or exogenous factors in these two populations which may help to explain both the distinct TP53 mutational pattern and the lower frequency obtained in the Polish group. The presence of missense mutations did not confer a worse clinical outcome in these subsets of NSCLC patients. However, patients whose tumors contained null TP53 gene mutations had a 5 month median disease-free survival time in contrast with 42 months in those patients without mutations (P=0.008). These findings suggest that loss of p53 function may enhance tumor progression in NSCLC patients independently of whether dominant negative TP53 missense mutations are present.

Hepatic biotransformation and antioxidant enzyme activities in Mediterranean fish from different habitat depths.

Marine fish are threatened by anthropogenic chemical discharges. However, knowledge on adverse effects on deep-sea fish or their detoxification capabilities is limited. Herein, we compared the basal activities of selected hepatic detoxification enzymes in several species (Solea solea, Dicentrarchus labrax, Trachyrhynchus scabrus, Mora moro, Cataetix laticeps and Alepocehalus rostratus) collected from the coast, middle and lower slopes of the Blanes Canyon region (Catalan continental margin, NW Mediterranean Sea). The xenobiotic-detoxifying enzymes analysed were the phase-I carboxylesterases (CbEs), and the phase-II conjugation activities uridine diphosphate glucuronyltransferase (UDPGT) and glutathione S-transferase (GST). Moreover, some antioxidant enzyme activities, i.e., catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GR), were also included in this comparative study. Because CbE activity is represented by multiple isoforms, the substrates α-naphthyl acetate (αNA) and ρ-nitrophenyl acetate (ρNPA) were used in the enzyme assays, and in vitro inhibition kinetics with dichlorvos were performed to compare interspecific CbE sensitivity. Activity of xenobiotic detoxification enzymes varied among the species, following a trend with habitat depth and body size. Thus, UDPGT and some antioxidant enzyme activities decreased in fish inhabiting lower slopes of deep-sea, whereas UDPGT and αNA-CbE activities were negatively related to fish size. A trend between CbE activities and the IC50 values for dichlorvos suggested S. solea and M. moro as potentially more sensitive to anticholinesterasic pesticides, and T. scabrus as the most resistant one. A principal component analysis considering all enzyme activities clearly identified the species but this grouping was not related to habitat depth or phylogeny. Although these results can be taken as baseline levels of the main xenobiotic detoxification enzymes in Mediterranean fish, further research is needed to evaluate their response to environmental contaminant exposure.

High levels of plasma FVIII and vWF in the toxic epidemic syndrome patients.

Factor VIII and von Willebrand factor proteins were evaluated in 115 patients having the chronic phase of the Toxic Epidemic Syndrome (TES), a new multisystemic disease probably caused by the ingestion of denatured rapeseed oil, and in 50 control volunteers. Higher circulating levels of factor VIII procoagulant activity (VIII:C) (158 +/- 58.4 U/dl), von Willebrand factor antigen (vWF:Ag) (166.1 +/- 55.5 U/dl) and von Willebrand factor ristocetin cofactor activity (vWF:RCo) (178.7 +/- 55.2 U/dl) were seen in TES patients (p less than 0.001, TES patients versus control subjects, for each parameter). The increased levels of vWF:Ag and vWF:RCo observed in TES patients correlated with the scleroderma like lesion of the skin, with the sicca syndrome and with Raynaud's phenomenon (p less than 0.01), but not with other clinical manifestations. The multimeric analysis of vWF in 92% of the TES patients was similar to that found in normal plasma, but in the remaining 8% a very slight increase of larger vWF multimers in plasma were observed. The raised levels of vWF found in TES patients in the chronic phase may reflect an "in vivo" vascular injury.