ABSTRACT
BACKGROUND: Incidence, clinical course, and fatality of spontaneous subarachnoid haemorrhage (SAH) are evolving, with prevalence of risk factors diminishing, implementation of early detection programs and strategies for priority aneurysm exclusion, technical refinement towards less invasive procedures, and improvements in neurocritical care. Modern epidemiological and prognostic data are lacking, especially in southern European and Mediterranean populations. METHODS: A prospective multicentre observational study on SAH was held in Catalonia, Northeast Spain, 2020-2022 (HSACat project). All public tertiary hospitals participated in a common registry. Primary endpoints were functional outcomes (modified Rankin Scale, mRS) and mortality at 12-months. Secondary aims included epidemiological data, flux of patients between referral and tertiary hospitals, diagnostic and treatment delays, and in-hospital complications. RESULTS: Of 550 SAH cases reported in Catalonia (2020-2022), 474 had a complete registry for analysis. Death rate was 20.6% during hospital admission and 26.9% at one year. Good functional outcome (mRS 0-2) was observed in 63.4%, 70.1% and 76.0% at 3, 6 and 12 months. Age at presentation was lower in men, smokers, and hypertensives (p<0.05). The female:male ratio was 3:2, except in non-aneurysmal group. Time from onset to tertiary-hospital admission was longer in rural than metropolitan zones (7.0h vs 4.7h, p<0.01). Aneurysm occlusion in the first 72h was achieved in 83.3%; mainly endovascularly (77.5%) than microsurgically (19.3%). CONCLUSION: Even when most patients received timely aneurysmal treatment, rates of case fatality are considerably high. Data provided by the HSAcat project may have public health repercussions and be used to guide prevention programs and screening strategies.
ABSTRACT
BACKGROUND: Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its prognostic impact on prognosis of young patients harboring a pathogenic variant (PV) in the BRCA1 and/or BRCA2 genes. PATIENTS AND METHODS: This international, multicenter, retrospective cohort study included young patients (aged ≤40 years) diagnosed with invasive breast cancer and harboring germline PVs in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest [disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS)] were first investigated according to hormone receptor expression (positive versus negative), and then according to breast cancer subtype [luminal A-like versus luminal B-like versus triple-negative versus human epidermal growth factor receptor 2 (HER2)-positive breast cancer]. RESULTS: From 78 centers worldwide, 4709 BRCA carriers were included, of whom 2143 (45.5%) had hormone receptor-positive and 2566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% versus 9.6%, P < 0.001), while the rate of second primary breast cancer was lower (9.1% versus 14.7%, P < 0.001) compared to patients with hormone receptor-negative disease. The 8-year DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive versus negative disease changed over time for DFS, BCSS, and OS (P < 0.05 for interaction of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-year DFS: 60.8% in luminal A-like versus 63.5% in triple-negative versus 65.5% in HER2-positive and 69.7% in luminal B-like subtype). CONCLUSIONS: In young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor-positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.
Subject(s)
BRCA1 Protein , BRCA2 Protein , Breast Neoplasms , Receptor, ErbB-2 , Receptors, Estrogen , Receptors, Progesterone , Humans , Female , Adult , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/mortality , Breast Neoplasms/metabolism , Retrospective Studies , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Receptor, ErbB-2/metabolism , Receptor, ErbB-2/genetics , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Prognosis , Disease-Free Survival , Young Adult , Germ-Line Mutation , Heterozygote , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolismABSTRACT
BACKGROUND: Giant pituitary adenomas (GPAs) are defined as tumors with ≥40 mm in any maximum diameter, and these tend to invade multiple intracranial compartments. Hence, treatment remains a surgical challenge. OBJECTIVE: To describe the clinical and surgical outcomes of the endoscopic endonasal approach (EEA) for GPA in a pituitary referral center in Latin America and to analyze associated predictive factors. METHODS: 37 patients with histologically-confirmed GPA treated solely through the EEA between a 2-year period were included. Preoperative and postoperative clinical and neuroimaging findings; surgical morbidity and mortality; and binary logistic regression analysis to assess predictive factors were analyzed. RESULTS: Preoperative visual impairment prevalence was 97.3%. Mean tumor volume was 32 cc and gross total resection rate was 40.5%. Favorable visual acuity and visual fields outcome rate was 75% and 82.9%, respectively. In the multivariate analysis, bilateral cavernous sinus invasion (P = 0.018) and postoperative cerebrospinal fluid (CSF) leak (P = 0.036) were associated with an unfavorable visual acuity outcome, while radiation therapy (P = 0.035) was for visual fields. Similarly, intraoperative CSF leak was a predictive factor for postoperative CSF leak (10.8%) (P = 0.042) and vascular injury (13.5%) (P = 0.048). CONCLUSIONS: In this first Mexican clinical series, we demonstrated that the EEA is a safe and effective technique for GPA, although early diagnosis and prompt intervention may promote further visual function preservation without significant endocrine morbidity.
Subject(s)
Adenoma , Pituitary Diseases , Pituitary Neoplasms , Humans , Pituitary Neoplasms/diagnostic imaging , Pituitary Neoplasms/surgery , Pituitary Neoplasms/complications , Adenoma/diagnostic imaging , Adenoma/surgery , Adenoma/complications , Nose/surgery , Postoperative Complications/epidemiology , Treatment Outcome , Retrospective StudiesABSTRACT
BACKGROUND: Most of large epidemiological studies on melanoma susceptibility have been conducted on fair skinned individuals (US, Australia and Northern Europe), while Southern European populations, characterized by high UV exposure and dark-skinned individuals, are underrepresented. OBJECTIVES: We report a comprehensive pooled analysis of established high- and intermediate-penetrance genetic variants and clinical characteristics of Mediterranean melanoma families from the MelaNostrum Consortium. METHODS: Pooled epidemiological, clinical and genetic (CDKN2A, CDK4, ACD, BAP1, POT1, TERT, and TERF2IP and MC1R genes) retrospective data of melanoma families, collected within the MelaNostrum Consortium in Greece, Italy and Spain, were analysed. Univariate methods and multivariate logistic regression models were used to evaluate the association of variants with characteristics of families and of affected and unaffected family members. Subgroup analysis was performed for each country. RESULTS: We included 839 families (1365 affected members and 2123 unaffected individuals). Pathogenic/likely pathogenic CDKN2A variants were identified in 13.8% of families. The strongest predictors of melanoma were ≥2 multiple primary melanoma cases (OR 8.1; 95% CI 3.3-19.7), >3 affected members (OR 2.6; 95% CI 1.3-5.2) and occurrence of pancreatic cancer (OR 4.8; 95% CI 2.4-9.4) in the family (AUC 0.76, 95% CI 0.71-0.82). We observed low frequency variants in POT1 (3.8%), TERF2IP (2.5%), ACD (0.8%) and BAP1 (0.3%). MC1R common variants (≥2 variants and ≥2 RHC variants) were associated with melanoma risk (OR 1.4; 95% CI 1.0-2.0 and OR 4.3; 95% CI 1.2-14.6, respectively). CONCLUSIONS: Variants in known high-penetrance genes explain nearly 20% of melanoma familial aggregation in Mediterranean areas. CDKN2A melanoma predictors were identified with potential clinical relevance for cancer risk assessment.
Subject(s)
Melanoma , Skin Neoplasms , Humans , Skin Neoplasms/epidemiology , Skin Neoplasms/genetics , Retrospective Studies , Mutation , Genetic Predisposition to Disease , Melanoma/epidemiology , Melanoma/genetics , Melanoma/pathology , Cyclin-Dependent Kinase Inhibitor p16/genetics , Germ-Line Mutation , Receptor, Melanocortin, Type 1/geneticsABSTRACT
The gelation process, elasticity, and mechanical recovery after shear were studied in mixed oleogels of ethylcellulose (EC), monoglycerides (MG), and candelilla wax (CW). EC oleogels produced without MG showed grainy texture due to incomplete dissolution of crystalline fractions of raw EC in the vegetable oil (150 °C). These fractions were eliminated by dissolving the raw EC/MG mixture in ethanol, evaporating the solvent, dispersing, and dissolving the solid residue in the vegetable oil (150 °C) prior gelation. The EC polymeric network, and MG, and CW crystals had a positive interaction on the elasticity of mixed oleogels. Mixed oleogels produced under static conditions showed a 100 % of elasticity recovery after shearing, a phenomenon associated with an EC interchain hydrogen bonding mediated by hydroxyl groups of MGs. This tentatively resulted from the formation of junction zones of the type EC-[MG]n-EC. The rheological behavior of these olegels was remarkably close to that of commercial shortenings.
ABSTRACT
Plastics pollution has been recognized as a serious environmental problem. Nevertheless, new plastic uses, and applications are still increasing. Among these new applications, three-dimensional resin printers have increased their use and popularity around the world showing a vertiginous annual-sales growth. However, this technology is also the origin of residues generation from the alcohol cleaning procedure at the end of each printing. This alcohol/resin mixture can originate unintentionally very small plastic particles that usually are not correctly disposed, and as consequence, could be easily released to the environment. In this work, the nanoparticle generation from 3D printer's cleaning procedure and their physicochemical characterization is reported. Nano-sized plastic particles are easily formed when the resin residues are dissolved in alcohol and placed under UV radiation from sunlight. These nanoparticles can agglomerate in seawater showing an average hydrodynamic diameter around 1 µm, whereas the same nanoparticles remain dispersed in ultrapure water, showing a hydrodynamic diameter of ≈300 nm. The formed nanoparticles showed an isoelectric point close to pH 2, which can facilitate their interaction with other positively charged pollutants. Thus, these unexpected plastic nanoparticles can become an environmental issue and public health risk.
Subject(s)
Environmental Pollutants , Nanoparticles , Water Pollutants, Chemical , Animals , Environmental Pollution , Ethanol , Microplastics , PlasticsSubject(s)
Meningeal Neoplasms , Meningioma , Evidence-Based Practice , Humans , Incidental FindingsABSTRACT
TITLE: Fistula arteriovenosa intracraneal pial con variz gigante.
Subject(s)
Arteriovenous Fistula/complications , Cerebral Veins/abnormalities , Intracranial Arteriovenous Malformations/complications , Varicose Veins/complications , Adult , Arteriovenous Fistula/diagnostic imaging , Arteriovenous Fistula/surgery , Humans , Intracranial Arteriovenous Malformations/diagnostic imaging , Intracranial Arteriovenous Malformations/surgery , Male , Varicose Veins/diagnosis , Varicose Veins/pathology , Varicose Veins/surgeryABSTRACT
AIM: To determine the causes of mortality in cases of brain haemorrhage among patients with arteriovenous malformations (AVM) treated in a tertiary hospital. PATIENTS AND METHODS: The patients with AVM who died over the period 1990-2014 were selected from a prospective register of vascular malformations. Demographic aspects, localisation of the AVM, associated aneurysms and previous treatments were reviewed. Three main causes of death were established: initial bleeding/rebleeding, those related with the treatment of the AVM and other causes not related with AVM. RESULTS: A total of 400 patients were treated for AVM, 216 (54%) with a ruptured AVM, of whom 26 (12.1%) died as a result of a brain haemorrhage. The mean age of the group of patients who died was 48.8 years (range: 8-78 years). Twenty (76.9%) were admitted in coma (Glasgow Coma Scale < 9). In five cases (19.2%), bleeding was due to an associated aneurysm. A very high percentage (38.5%) had the AVM in the posterior fossa. Three patients had previously received non-curative treatments for the AVM in other medical centres. Of the total number, six (23.1%) received endovascular/surgical treatment in our hospital, and we have assumed that, due to the indication or owing to the time in which it was carried out, the cause of death was treatment-related, although two young patients underwent surgery with bilateral mydriasis. One patient died due to an associated glioblastoma, and the others, 19 (76%), due to rebleeding or to the initial brain damage. CONCLUSION: Knowing the causes of mortality can help improve the clinical outcome, above all in cases in which an early treatment could be indicated.
TITLE: Causas de la mortalidad hospitalaria por hemorragia cerebral en pacientes con malformacion arteriovenosa.Objetivo. Conocer las causas de la mortalidad en la hemorragia cerebral de los pacientes con malformaciones arteriovenosas (MAV) tratadas en un hospital terciario. Pacientes y metodos. De un registro prospectivo de malformaciones vasculares se han seleccionado los pacientes que fallecieron con MAV en el periodo 1990-2014. Se han revisado aspectos demograficos, localizacion de la MAV, aneurismas asociados y tratamientos previos. Se han establecido tres causas principales de muerte: sangrado inicial/resangrado, relacionadas con el tratamiento de la MAV y otras causas no relacionadas con la MAV. Resultados. Se trato a 400 pacientes de MAV, 216 (54%) con MAV rotas, de los que fallecieron 26 (12,1%) por hemorragia cerebral. La media de edad del grupo de pacientes fallecidos fue de 48,8 años (rango: 8-78 años). Veinte (76,9%) ingresaron en coma (escala de coma de Glasgow < 9). En cinco casos (19,2%), el sangrado se debio a un aneurisma asociado. Un porcentaje muy elevado (38,5%) tenia la MAV en la fosa posterior. Tres pacientes habian recibido previamente en otros centros tratamientos no curativos de la MAV. Del total, seis (23,1%) recibieron tratamiento endovascular/quirurgico en nuestro hospital, y hemos asumido que, por la indicacion o por el momento en que se realizo, la causa de la muerte se relacionaba con el tratamiento, aunque dos pacientes jovenes se operaron con midriasis bilateral. Un paciente fallecio por un glioblastoma asociado, y el resto, 19 (76%), por el resangrado o el daño cerebral inicial. Conclusion. El conocimiento de las causas de mortalidad puede contribuir a mejorar el resultado clinico, sobre todo en los casos en que podria estar indicado un tratamiento precoz.
Subject(s)
Cause of Death , Hospital Mortality , Intracranial Arteriovenous Malformations/complications , Intracranial Hemorrhages/mortality , Adolescent , Adult , Aged , Child , Embolization, Therapeutic , Female , Glioblastoma/complications , Humans , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/epidemiology , Intracranial Aneurysm/etiology , Intracranial Arteriovenous Malformations/epidemiology , Intracranial Arteriovenous Malformations/surgery , Intracranial Arteriovenous Malformations/therapy , Intracranial Hemorrhages/diagnostic imaging , Intracranial Hemorrhages/etiology , Intracranial Hemorrhages/therapy , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Prospective Studies , Registries , Socioeconomic Factors , Spain/epidemiology , Tertiary Care Centers/statistics & numerical data , Tomography, X-Ray Computed , Young AdultABSTRACT
The aim of this study was to quantify the content of polysaccharides of edible tender cladodes (nopalitos) of three species of Opuntia and to evaluate the rheological flow behavior of isolated polysaccharides. A completely randomized experimental design was used to characterize a wild (O. streptacantha), a semidomesticated (O. megacantha) and a domesticated (O. ficus-indica) species. Mucilage content was higher (4.93 to 12.43 g 100 g-1 dry matter), tightly bound hemicelluloses were lower (3.32 to 1.81 g 100 g-1 dry matter) and pectins and loosely bound hemicelluloses were not different in wild than in domesticated species. Aqueous solution/suspensions of mucilage, pectins, hemicellulose and cellulose of all species showed non-Newtonian behavior under simple shear flow. The flow behavior of the structural polysaccharides was well described by the Ostwald de-Waele model. Pectins and mucilages exhibited the highest consistency indexes (K values ranged from 0.075 to 0.177 Pasn) with a moderated shear-thinning behavior (n values ranged from 0.53 to 0.67). Cellulose dispersions exhibited the most shear-thinning behavior (n values ranged from 0.17 to 0.41) and hemicelluloses showed a tendency to Newtonian flow (n values ranged from 0.82 to 0.97). The rheological flow properties of these polysaccharides may be useful to improve the textural and sensory qualities of some foods and pharmaceutical materials. Moreover, they can emerge as functional ingredients mainly due to the nutraceutical properties that have been attributed to nopalitos.
Subject(s)
Opuntia/chemistry , Polysaccharides/chemistry , Cellulose/chemistry , Models, Theoretical , Opuntia/classification , Pectins/chemistry , Plant Mucilage/chemistry , RheologyABSTRACT
Hepatocellular carcinoma develops in cirrhotic liver. The nitric oxide (NO) synthase type III (NOS-3) overexpression induces cell death in hepatoblastoma cells. The study developed gene therapy designed to specifically overexpress NOS-3 in cultured hepatoma cells, and in tumors derived from orthotopically implanted tumor cells in fibrotic livers. Liver fibrosis was induced by CCl4 administration in mice. The first-generation adenoviruses were designed to overexpress NOS-3 or green fluorescent protein, and luciferase complementary DNA under the regulation of murine alpha-fetoprotein (AFP) and Rous Sarcoma Virus (RSV) promoters, respectively. Both adenovirus and Hepa 1-6 cells were used for in vitro and in vivo experiments. Adenoviruses were administered through the tail vein 2 weeks after orthotopic tumor cell implantation. AFP-NOS-3/RSV-luciferase increased oxidative-related DNA damage, p53, CD95/CD95L expression and caspase-8, -9 and -3 activities in cultured Hepa 1-6 cells. The increased expression of CD95/CD95L and caspase-8 activity was abolished by Nω-nitro-l-arginine methyl ester hydrochloride, p53 and CD95 small interfering RNA. AFP-NOS-3/RSV-luciferase adenovirus increased cell death markers, and reduced cell proliferation of established tumors in fibrotic livers. The increase of oxidative/nitrosative stress induced by NOS-3 overexpression induced DNA damage, p53, CD95/CD95L expression and cell death in hepatocellular carcinoma cells. The effectiveness of the gene therapy has been demonstrated in vitro and in vivo.
Subject(s)
Carcinoma, Hepatocellular/therapy , Gene Expression Regulation, Neoplastic , Genetic Therapy/methods , Liver Neoplasms/therapy , Nitric Oxide Synthase Type III/genetics , Adenoviridae/genetics , Animals , Carcinoma, Hepatocellular/genetics , Caspase 3/genetics , Caspase 3/metabolism , Caspase 8/genetics , Caspase 8/metabolism , Caspase 9/genetics , Caspase 9/metabolism , Cell Line, Tumor , Cell Proliferation , DNA Damage , DNA, Complementary/genetics , DNA, Complementary/metabolism , Disease Models, Animal , Fas Ligand Protein/genetics , Fas Ligand Protein/metabolism , Genetic Vectors , Liver/cytology , Liver/metabolism , Liver Cirrhosis/genetics , Liver Cirrhosis/therapy , Liver Neoplasms/genetics , Mice , NG-Nitroarginine Methyl Ester/metabolism , Nitric Oxide Synthase Type III/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Rous sarcoma virus/genetics , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , alpha-Fetoproteins/genetics , alpha-Fetoproteins/metabolismABSTRACT
Nitric oxide (NO) plays a relevant role during cell death regulation in tumor cells. The overexpression of nitric oxide synthase type III (NOS-3) induces oxidative and nitrosative stress, p53 and cell death receptor expression and apoptosis in hepatoblastoma cells. S-nitrosylation of cell death receptor modulates apoptosis. Sorafenib is the unique recommended molecular-targeted drug for the treatment of patients with advanced hepatocellular carcinoma. The present study was addressed to elucidate the potential role of NO during Sorafenib-induced cell death in HepG2 cells. We determined the intra- and extracellular NO concentration, cell death receptor expression and their S-nitrosylation modifications, and apoptotic signaling in Sorafenib-treated HepG2 cells. The effect of NO donors on above parameters has also been determined. Sorafenib induced apoptosis in HepG2 cells. However, low concentration of the drug (10nM) increased cell death receptor expression, as well as caspase-8 and -9 activation, but without activation of downstream apoptotic markers. In contrast, Sorafenib (10 µM) reduced upstream apoptotic parameters but increased caspase-3 activation and DNA fragmentation in HepG2 cells. The shift of cell death signaling pathway was associated with a reduction of S-nitrosylation of cell death receptors in Sorafenib-treated cells. The administration of NO donors increased S-nitrosylation of cell death receptors and overall induction of cell death markers in control and Sorafenib-treated cells. In conclusion, Sorafenib induced alteration of cell death receptor S-nitrosylation status which may have a relevant repercussion on cell death signaling in hepatoblastoma cells.
Subject(s)
Antineoplastic Agents/pharmacology , Gene Expression Regulation, Neoplastic , Niacinamide/analogs & derivatives , Phenylurea Compounds/pharmacology , Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism , Receptors, Tumor Necrosis Factor, Type I/metabolism , Signal Transduction , Caspase 3/genetics , Caspase 3/metabolism , Caspase 8/genetics , Caspase 8/metabolism , Caspase 9/genetics , Caspase 9/metabolism , Cell Death/drug effects , Cysteine/analogs & derivatives , Cysteine/chemistry , Cysteine/pharmacology , Hep G2 Cells , Humans , Niacinamide/pharmacology , Nitric Oxide/chemistry , Nitric Oxide/pharmacology , Nitric Oxide Donors/chemistry , Nitric Oxide Donors/pharmacology , Nitric Oxide Synthase Type III/genetics , Nitric Oxide Synthase Type III/metabolism , Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics , Receptors, Tumor Necrosis Factor, Type I/genetics , S-Nitrosothiols/chemistry , S-Nitrosothiols/pharmacology , SorafenibABSTRACT
Cannabinoids are key regulators of vascular tone, some of the mechanisms involved include the activation of cannabinoid receptor types 1 and 2 (CB); the transient receptor potential cation channel, subfamily V, member 1 (TRPV1); and non-(CB(1))/non-CB2 receptors. Here, we used the potent, selective CB(1) agonist arachidonylcyclopropylamide (ACPA) to elucidate the mechanism underlying vascular tone regulation. Immunohistochemistry and confocal microscopy revealed that CB(1) was expressed in smooth muscle and endothelial cells in rat aorta. We performed isometric tension recordings in aortic rings that had been pre-contracted with phenylephrine. In these conditions, ACPA caused vasorelaxation in an endothelium-independent manner. To confirm that the effect of ACPA was mediated by CB(1) receptor, we repeated the experiment after blocking these receptors with a selective antagonist, AM281. In these conditions, ACPA did not cause vasorelaxation. We explored the role of K(+) channels in the effect of ACPA by applying high-K(+) solution to induce contraction in aortic rings. In these conditions, the ACPA-induced vasorelaxation was about half that observed with phenylephrine-induced contraction. Thus, K(+) channels were involved in the ACPA effect. Furthermore, the vasorelaxation effect was similarly reduced when we specifically blocked calcium-activated potassium channel subunit alpha-1 (KCa1.1) (MaxiK; BKCa) prior to adding ACPA. Finally, ACPA-induced vasorelaxation was also diminished when we specifically blocked the calcium channel, voltage-dependent, L type, alpha 1C subunit (Ca(v)1.2). These results showed that ACPA activation of CB(1) in smooth muscle caused vasorelaxation of aortic rings through a mechanism involving the activation of K(Ca)1.1 and the inhibition of Ca(v)1.2.
Subject(s)
Arachidonic Acids/pharmacology , Calcium Channels, L-Type/metabolism , Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/metabolism , Receptor, Cannabinoid, CB1/metabolism , TRPV Cation Channels/metabolism , Vasodilation/physiology , Animals , Aorta, Thoracic/drug effects , Aorta, Thoracic/metabolism , Calcium/metabolism , Dose-Response Relationship, Drug , Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/agonists , Male , Organ Culture Techniques , Rats , Rats, Wistar , Receptor, Cannabinoid, CB1/agonists , TRPV Cation Channels/agonists , Vasodilation/drug effectsABSTRACT
Se determinó la presencia de residuos de rodenticidas anticoagulantes por cromatografía de líquidos acoplada a espectrometría de masas de triple cuadrupolo en el hígado de 61 aves rapaces muertas provenientes del Centro de Recuperación de Fauna Silvestre de Tafira (Gran Canaria), pertenecientes a 5 especies de las 11 presentes en el archipiélago canario. Se encontraron residuos en 42 animales (69%) si bien en sólo 1 de ellos se consideró la intoxicación por rodenticidas como causa primaria de muerte, según los datos clínicos, analíticos y de necropsia. De las rapaces estudiadas, fueron las especies Tyto alba y Accipiter nisus las que más frecuentemente presentaron residuos de anticoagulantes (85% y 89% respectivamente). Se detectaron residuos de 5 anticoagulantes, todos ellos de segunda generación, siendo la bromadiolona las más frecuentemente detectada, seguida del brodifacoum y del difenacoum. Un elevado número de las muestras positivas (63%) presentó más de un residuo de anticoagulantes en su hígado, habiéndose encontrado mezclas de hasta 4 productos diferentes. Llamó la atención que la mayoría de los animales que ingresaron en el centro de recuperación por politraumatismo por colisión presentaba residuos de uno o varios anticoagulantes, así como que rapaces que se alimentan principalmente de pájaros también presentaron frecuentemente residuos de estos compuestos. Los resultados de este estudio sugieren que el elevado uso de rodenticidas anticoagulantes en el medio natural implica su incorporación a la cadena trófica, viéndose afectadas especies de fauna silvestre en las que estos productos podrían producir efectos adversos. Esto implica que la aplicación de rodenticidas anticoagulantes en espacios abiertos supone una amenaza para el estado de conservación de la biodiversidad de las Islas Canarias (AU)
Anticoagulant rodenticide (AR) levels were studied in liver of 61 dead raptors of five of the eleven species of the Canary Islands. The animals were delivered to our laboratory from the Centro de Recuperación de Fauna Silvestre de Tafira (Gran Canaria). Anticoagulant residues were detected in 42 (69%) of the studied animals, but only 1 may have died by AR poisoning according to the clinical information, necropsy findings and toxicological analysis. Of the studied raptors Tyto alba and Accipiter nisus were the species with more frequency and higher levels of anticoagulants (85% and 89%). Residues of 5 anticoagulants were detected, all of them of second generation, being the most frequently detected bromadiolone, brodifacoum and difenacoum. A large number of samples (63%) presented more than one residue of anticoagulants in their livers, and we have found as much as 4 different residues in one animal. It was remarkable that most of the animals that had suffered polytraumatism by collision presented residues of anticoagulants, and that species such as the hawk that mainly eat birds frequently presented anticoagulant residues. The results of this study suggest that the high use of anticoagulant rodenticides in the natural environment involves their incorporation into the food chain, and this can affect wildlife species in which these products may cause side effects. This means that the application of anticoagulant rodenticides in open spaces poses a threat to the conservation status of biodiversity in the Canary Islands (AU)
Subject(s)
Animals , Birds/classification , Anticoagulants/toxicity , Waste Products/adverse effects , Insecticides/toxicity , 35510 , Toxicity Measurements , Pesticides/adverse effects , Pesticides/toxicity , Pesticide Residues/adverse effects , Pesticide Residues/toxicity , Hazardous Waste/adverse effects , Chromatography, Liquid/methods , Chromatography, Liquid/standards , Chromatography, Liquid , Gas Chromatography-Mass Spectrometry/methods , Gas Chromatography-Mass Spectrometry , Cholinesterase Inhibitors/toxicityABSTRACT
En el presente estudio se ha evaluado el grado de contaminación por contaminantes orgánicos persistentes (COPs) en 193 ejemplares de tortuga boba (Caretta caretta) varadas en las Islas Canarias entre 2007-2011. La cuantificación en plasma de los niveles de pesticidas organoclorados (POCs), bifenilos policlorados (PCBs) e hidrocarburos aromáticos policíclicos (PAHs) se realizó mediante GC-MS. Todas las muestras analizadas presentaron niveles cuantificables de alguno de los COPs incluidos en el estudio. El grupo de COPs que presentó mayores niveles fue el de los PAHs (alcanzando la carga total de PAHs 6,45 ng/ml), siendo el fenantreno el hidrocarburo más frecuentemente detectado y a concentraciones más altas, lo que indica el origen petrogénico de estos contaminantes. La contaminación por PCBs alcanzó niveles menores (3,84 ng/ml), predominando el grupo de los hexaclorobifenilos (PCB-153 y PCB- 138 principalmente). Los niveles de contaminación por POCs fueron también bajos alcanzando valores de 1,67 ng/ml, siendo el principal metabolito del DDT, el p,p´-DDE el compuesto más frecuentemente detectado (89,6%) y a más altas concentraciones (0,68 ng/ml). Fue evidente una asociación inversa entre el tamaño de las tortugas y la carga de PCBs y PAHs. Asimismo existieron niveles más altos de contaminación por COPs en los años 2009 y 2010. Este trabajo evalúa por vez primera la presencia de PAHs en sangre de tortugas varadas y nuestros resultados parecen indicar que esta metodología y esta especie animal pueden ser muy útiles para monitorizar la presencia de contaminación por derivados del petróleo en el medio acuático (AU)
This study assessed the degree of contamination by persistent organic pollutants (POPs) present in 193 specimens of loggerhead turtle (Caretta caretta) stranded in the Canary Islands between 2007-2011. Quantification of plasma levels of organochlorine pesticides (POCs), polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) were performed by GC-MS. All samples tested showed measurable levels of several of the POPs included in the study. PAHs was the group that showed the highest levels (total burden of PAHs = 6.45 ng/ml), being phenanthrene the compound most frequently detected and at higher concentrations, indicating the petrogenic origin of these contaminants. PCBs contamination reached lower levels (3.84 ng/ml), dominating the group of hexachlorobiphenyls (PCB-153 and PCB-138 in particular). The pollution levels were also low in the subgroup of POCs, reaching values of 1.67 ng/ml, and being the main metabolite of DDT, p, p'-DDE the compound most frequently detected (89.6%) and at highest concentrations (0.68 ng/ml). There was a clear inverse association between the size of the turtles and the burden of PCBs and PAHs. There were also higher levels of POPs in 2009 and 2010 than in the other years. This study evaluates for the first time the presence of PAHs in stranded turtles blood and our results suggest that this methodology and this animal species can be very useful for monitoring the presence of petroleum derivatives contamination in the aquatic environment (AU)
Subject(s)
Animals , Male , Female , Turtles/physiology , Organic Chemicals/toxicity , Organic Pollutants , Garbage , Insecticides, Organochlorine/adverse effects , Insecticides, Organochlorine/prevention & control , Polychlorinated Biphenyls/toxicity , Polybrominated Biphenyls/toxicity , Pesticides/toxicity , Pesticide Residues/toxicity , Hydrocarbons, Aromatic/toxicity , Polycyclic Compounds/toxicity , Polycyclic Aromatic Hydrocarbons/toxicityABSTRACT
En el Hospital Universitario de Canarias pusimos en marcha, en mayo de 2008, un protocolo de tratamiento de inducción para pacientes hipersensibilizados que reciben injerto renal de cadáver utilizando inmunoglobulinas intravenosas, plasmaféresis y rituximab más una inmunosupresión triple con prednisona, tacrolimus y micofenolatomofetil. Presentamos los resultados de 4 pacientes. Todo sellos presentaban una tasa de anticuerpos anti-HLA (PARA por CDC) superior al 75%, llevaban en lista de espera de 4a 17 años, el tiempo de seguimiento posterior al trasplante fue de 10-14 meses y la supervivencia de paciente y del injerto en este período fue del 100%. Sólo un paciente sufrió un rechazo agudo mediado por anticuerpos y otro uno celular, en ambos casos reversibles con el tratamiento. En la evolución no se objetivó aparición de novo de anticuerpos donante-específicos. Todos los pacientes habían reducido significativamente el número de células CD19+ después de la infusión de rituximab. No se han detectado síntomas neurológicos indicativos de leucoencefalopatía multifocal progresiva ni infecciones virales graves después del trasplante y tampoco se han observado efectos secundarios inmediatos tras la administración de la medicación. En resumen, el tratamiento de inducción combinado con inmunoglobulinas, plasmaféresis y rituximab en pacientes (..) (AU)
In our Universitary Hospital of Canarias we iniciated in May2008 a induction therapy protocol for sensitized patients receiving cadaveric renal graft using intravenous immunoglobulins, plasmapheresis and rituximab plusimmuno suppression with prednisone, tacrolimus and mycophenolate mofetil. We present the results of four patients. Everyone had anti-HLA antibodies rate (PRA by CDC) more than 75%, were on a waiting list during 4 to 17 years and follow-up time was 10-14 months after transplantation. Patient and graft survival in this period was 100%. Only one patient suffered a humoral acute rejection and another one cellular rejection, in both cases reversible with treatment. During the first year, no evidence of de novo donor-specific antibodies was detected. All patients had significantly reduced the CD19+ cells percentage after infusion of rituximab. Neurological symptoms suggestive of progressive multifocal leukoencephalopathy or serious viral infections after transplantation have not been observed. Additionally, no immediate side effects were observed after administration of medication. In summary, induction therapy by combining immunoglobulin, plasmapheresis and rituximab in hypersensitive patients allows the realization of deceased kidney transplantation with good results in the short and medium-term without serious side effects. It remains to know whether this success will continue in the long term (AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Kidney Transplantation/methods , Immunoglobulins/administration & dosage , Plasmapheresis/methods , Antibodies, Monoclonal/administration & dosage , Transplantation Conditioning/methods , Induction Chemotherapy/methods , Hypersensitivity/drug therapy , Nephritis, Interstitial/therapy , Diabetic Nephropathies/therapy , Polycystic Kidney Diseases/therapyABSTRACT
In our Universitary Hospital of Canarias we iniciated in May 2008 a induction therapy protocol for sensitized patients receiving cadaveric renal graft using intravenous immunoglobulins, plasmapheresis and rituximab plus immunosuppression with prednisone, tacrolimus and mycophenolate mofetil. We present the results of four patients. Everyone had anti-HLA antibodies rate (PRA by CDC) more than 75%, were on a waiting list during 4 to 17 years and follow-up time was 10-14 months after transplantation. Patient and graft survival in this period was 100%. Only one patient suffered a humoral acute rejection and another one cellular rejection, in both cases reversible with treatment. During the first year, no evidence of de novo donor-specific antibodies was detected. All patients had significantly reduced the CD19+ cells percentage after infusion of rituximab. Neurological symptoms suggestive of progressive multifocal leukoencephalopathy or serious viral infections after transplantation have not been observed. Additionally, no immediate side effects were observed after administration of medication. In summary, induction therapy by combining immunoglobulin, plasmapheresis and rituximab in hypersensitive patients allows the realization of deceased kidney transplantation with good results in the short and medium-term without serious side effects. It remains to know whether this success will continue in the long term.