RESUMEN
Pharmacology has broadened its scope considerably in recent decades. Initially, it was of interest to chemists, doctors and pharmacists. In recent years, however, it has been incorporated into the teaching of biologists, molecular biologists, biotechnologists, chemical engineers and many health professionals, among others. Traditional teaching methods, such as lectures or laboratory work, have been superseded by the use of new pedagogical approaches to enable a better conceptualization and understanding of the discipline. In this article, we present several new methods that have been used in Spanish universities. Firstly, we describe a teaching network that has allowed the sharing of pedagogical innovations in Spanish universities. A European experience to improve prescribing safety is described in detail. The use of popular films and medical TV series in biomedical students shows how these audiovisual resources can be helpful in teaching pharmacology. The use of virtual worlds is detailed to introduce this new approach to teaching. The increasingly important area of the social aspects of pharmacology is also considered in two sections, one devoted to social pharmacology and the other to the use of learning based on social services to improve understanding of this important area. Finally, the use of Objective Structured Clinical Evaluation in pharmacology allows to know how this approach can help to better evaluate clinical pharmacology students. In conclusion, this article allows to know new pedagogical methods resources used in some Spanish universities that may help to improve the teaching of pharmacology.
Asunto(s)
Farmacología Clínica , Farmacología , Humanos , Aprendizaje , Farmacología Clínica/educación , Personal de Salud , Farmacología/educaciónRESUMEN
BACKGROUND AND OBJECTIVE: The sequence of prenatal growth restraint and postnatal catch-up growth may lead to hepato-visceral adiposity, insulin resistance and low-grade inflammation before the onset of puberty. In prepubertal children born appropriate for gestational age (AGA) or small for gestational age (SGA), we assessed potential relationships between the aforementioned sequence and liver volume. SUBJECTS/METHODS: The study population consisted of 86 children (41 AGA and 45 SGA with catch-up growth; age (mean±s.e.m.), 8.5±0.1 years), recruited into two prospective longitudinal studies. Anthropometry, endocrine-metabolic variables and inflammatory and hepatic markers were assessed, along with liver volume, hepatic adiposity and abdominal fat partitioning (by magnetic resonance imaging). RESULTS: AGA and SGA children differed in hepato-visceral adiposity, but had similar liver volumes. Boys had larger livers than girls, and higher sex hormone binding globulin and inflammation markers. Liver volume correlated with height Z-score, body mass index Z-score, HOMA-IR (homeostasis model assessment-insulin resistance) and with subcutaneous and visceral fat, but not with birth weight Z-score or with hepatic adiposity. Height, visceral fat, gender and HOMA-IR were major determinants of liver volume, together explaining 61% of its variance. CONCLUSIONS: The trajectory from prenatal restraint, via postnatal catch-up, to hepato-visceral adiposity and insulin resistance does not appear to be detectably influenced by prepubertal alterations of liver volume. Further follow-up will disclose the potential role of liver volume in the pubertal segment of this trajectory, and whether the augmented fat content and visceral adiposity in SGA subjects is followed by the development of metabolic syndrome and hepatic dysfunction in adulthood.
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Hígado Graso/patología , Recién Nacido Pequeño para la Edad Gestacional/fisiología , Grasa Intraabdominal/patología , Hígado/patología , Obesidad Infantil/epidemiología , Niño , Femenino , Gráficos de Crecimiento , Humanos , Recién Nacido , Estudios Longitudinales , Masculino , Análisis Multivariante , Sobrepeso/epidemiología , Sobrepeso/patología , Obesidad Infantil/patología , Estudios Prospectivos , Factores de RiesgoRESUMEN
In major surgery, the implementation of multidisciplinary, multimodal and individualized strategies, collectively termed Patient Blood Management, aims to identify modifiable risks and optimise patients' own physiology with the ultimate goal of improving outcomes. Among the various strategies utilized in Patient Blood Management, timely detection and management of preoperative anaemia is most important, as it is in itself a risk factor for worse clinical outcome, but also one of the strongest predisposing factors for perioperative allogeneic blood transfusion, which in turn increases postoperative morbidity, mortality and costs. However, preoperative anaemia is still frequently ignored, with indiscriminate allogeneic blood transfusion used as a 'quick fix'. Consistent with reported evidence from other medical specialties, this imprudent practice continues to be endorsed by non-evidence based misconceptions, which constitute serious barriers for a wider implementation of preoperative haemoglobin optimisation. We have reviewed a number of these misconceptions, which we unanimously consider should be promptly abandoned by health care providers and replaced by evidence-based strategies such as detection, diagnosis and proper treatment of preoperative anaemia. We believe that this approach to preoperative anaemia management may be a viable, cost-effective strategy that is beneficial both for patients, with improved clinical outcomes, and for health systems, with more efficient use of finite health care resources.
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Anemia/diagnóstico , Anemia/terapia , Hemoglobinas/análisis , Cuidados Preoperatorios , Procedimientos Quirúrgicos Operativos , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Transfusión Sanguínea/estadística & datos numéricos , Femenino , Humanos , Masculino , Factores de RiesgoRESUMEN
BACKGROUND: Postoperative blood loss may be a risk factor for allogeneic blood transfusion (ABT) in patients undergoing subcapital hip fracture (SHF) repair. We investigated the utility and costs of using a low-vacuum reinfusion drain (Bellovac ABT) within a blood management protocol for reducing ABT requirements in consecutive SHF. METHODS: The blood management protocol consisted of the application of a restrictive transfusion trigger (Hb < 8 g/dl), the peri-operative administration of IV iron sucrose (3 × 200 mg/48 h) ± recombinant erythropoietin (1 × 40 000 IU sc) and the use of Bellovac ABT (Group 2, n = 117). An immediate previous SHF series managed without Bellovac ABT served as control (Group 1, n = 138). RESULTS: Overall, 72 out of 255 (28%) received at least one ABT unit (2·1 ± 1·0 U/transfused patient) without differences between groups. However, in the subgroup of patients with admission Hb < 13 g/dl, the use of Bellovac ABT reduced postoperative ABT rates (16% vs. 46%, for groups 2 and 1, respectively; P = 0·001), although only 3 were reinfused, and was cost-saving. The use of Bellovac ABT also resulted in fewer wound bleeding complications, but there were no differences in Hb at postoperative days 7 and 30 between groups. CONCLUSIONS: In SHF patients with admission Hb < 13 g/dl and managed with peri-operative IV iron ± recombinant erythropoietin plus restrictive transfusion indication, the use of Bellovac ABT was associated with reduced ABT requirements, without increasing postoperative complications, and cost-savings.
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Transfusión Sanguínea/métodos , Fracturas de Cadera/cirugía , Hemorragia Posoperatoria/prevención & control , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Eritropoyetina/administración & dosificación , Femenino , Humanos , Hierro/administración & dosificación , Masculino , Succión , VacioRESUMEN
BACKGROUND AND PURPOSE: Patients with the non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) may develop atypical parkinsonian syndromes. However, there is no current biomarker to assess which patients are at high risk of developing parkinsonism. 123I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT)-SPECT detects striatal dopamine dysfunction in vivo. The objective of the present study was to study whether non-fluent/agrammatic patients without parkinsonism at baseline present decreased striatal 123I-FP-CIT uptake. METHODS: Visual and semi-quantitative assessments of the striatal 123I-FP-CIT uptake ratio were carried out in 15 patients with nfvPPA, eight patients with the logopenic variant of PPA (lvPPA) and 18 controls. To rule out progranulin mutations or underlying Alzheimer's disease (AD), serum progranulin levels and cerebrospinal fluid (CSF) biomarkers of AD (Aß42 , total-tau, phosphorylated-tau181 ) were determined. A second 123I-FP-CIT-SPECT analysis in the biomarker-enriched groups was also carried out. RESULTS: Patients with nfvPPA presented reduced striatal 123I-FP-CIT binding, especially in the left hemisphere (P = 0.002), compared with controls. All lvPPA patients had normal striatal 123I-FP-CIT uptake. 123I-FP-CIT striatal binding in nfvPPA patients with normal progranulin and CSF biomarker levels (nfvPPA/bio-) was also significantly reduced (P < 0.05) compared with lvPPA patients with positive AD biomarkers. Sixty-four per cent (9/14) of nfvPPA patients and 80% of nfvPPA/bio- patients (8/10) showed a diminished individual left striatal 123I-FP-CIT uptake ratio. On follow-up, seven nfvPPA/bio- patients developed parkinsonism (median 1.9 years; range 1.2-2.9), six of them with baseline reduced 123I-FP-CIT uptake. CONCLUSIONS: Reduced striatal tracer uptake in nfvPPA patients prior to clinical parkinsonism can be detected by 123I-FP-CIT-SPECT, especially in those with nfvPPA/bio-, suggesting subclinical nigrostriatal degeneration. Decreased striatal 123I-FP-CIT binding might identify PPA patients at increased risk of developing atypical parkinsonian syndromes, probably related to tau-pathology.
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Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Neostriado/metabolismo , Enfermedad de Parkinson/metabolismo , Afasia Progresiva Primaria no Fluente/metabolismo , Tomografía Computarizada de Emisión de Fotón Único/métodos , Tropanos , Anciano , Biomarcadores , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neostriado/diagnóstico por imagen , Enfermedad de Parkinson/diagnóstico por imagen , Afasia Progresiva Primaria no Fluente/diagnóstico por imagenRESUMEN
Reported values of D(2) receptor occupancy (RO) achieved by antipsychotic drugs tend to be lower when measured with (123)I-IBZM SPECT than with (11)C-Raclopride PET. Image degrading factors such as attenuation, distance-dependent collimator response and scatter could account for this difference. While attenuation correction is routinely applied to SPECT images, the other degradations are not usually accounted for. The aim of this work was to assess the impact of scatter correction on D(2) RO quantification with (123)I-IBZM SPECT, and to compare the results of both corrected and un-corrected SPECT values with (11)C-Raclopride PET measurements. Phantom experiments as well as within-subject human data from a previous study were used for this purpose. SPECT images were reconstructed using filtered back-projection including attenuation correction (FBP(A)), ordered subsets expectation maximization including attenuation and point spread function corrections (OSEM(A+PSF)) and ordered subsets expectation maximization including attenuation, point spread function and scatter corrections (OSEM(A+PSF+SCT)). PET images were reconstructed using the FBP algorithm and corrected for attenuation, scatter, random coincidences and dead time. Quantification of receptor availability was performed using the tissue ratio at pseudoequilibrium for SPECT, and the simplified reference tissue model (SRTM) for PET. Analysis was performed using both occipital cortex (occ) and cerebellum (cer) as reference regions for both modalities. When images were reconstructed using FBP(A), SPECT D(2) RO values were significantly lower as compared with PET leading to a D(2) RO difference of -20% (CI(95%): -13, -27%) (occ) and -23% (CI(95%): -14, -31%) (cer). When images were reconstructed using OSEM(A+PSF), SPECT D(2) RO values were also lower as compared with PET leading to a D(2) RO difference of -21% (CI(95%): -14, -27%) (occ) and -24% (CI(95%): -18, -30%) (cer). When images were reconstructed using OSEM(A+PSF+SCT), the D(2) RO bias was reduced to -6% (CI(95%): 0, -13%) (occ) and -11% (CI(95%): -4, -18%) (cer). These data suggest that the scatter correction plays a major role in explaining the differences between D(2) RO measurements using (123)I-IBZM SPECT and (11)C-Raclopride PET.
Asunto(s)
Benzamidas , Tomografía de Emisión de Positrones/métodos , Pirrolidinas , Racloprida , Receptores de Dopamina D2/metabolismo , Procesamiento de Señales Asistido por Computador , Tomografía Computarizada de Emisión de Fotón Único/métodos , Adulto , Algoritmos , Antipsicóticos/farmacología , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Mapeo Encefálico/instrumentación , Mapeo Encefálico/métodos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Modelos Neurológicos , Fantasmas de Imagen , Tomografía de Emisión de Positrones/instrumentación , Dispersión de Radiación , Tomografía Computarizada de Emisión de Fotón Único/instrumentaciónRESUMEN
Several gene delivery reagents were analyzed for their transfection efficiency. Genes studied belonged to the class of mammalian proteins termed regulators of G-protein signaling (RGS), ranged in size up to 2.2 Kb long and were transfected into the NG108-15, SH-SY5Y and CHO-K1 cell lines. Prior to transfection, genes were cloned into a nonviral vector pcDNA 6.2/EmGFP, so as to express a green fluorescent protein tag at the 3' end. Flow cytometry was used to analyze cell fluorescent activity and thereby transfection efficiency. Gene delivery reagents Lipofectamine 2000 and ExGen 500 produced more effective transfection in NG108-15 cells whereas Lipofectamine 2000, ExGen 500 and TurboFectin 8.0 were more effective in CHO-K1 cells. In both these cell lines, transfection efficiency reached 60-80%. In SH-SY5Y cells, TurboFectin 8.0 produced the best transfection result; however efficiency level was only 5%. Gene size had no effect on transfection efficiency. Unlike Lipofectamine 2000, cells transfected using ExGen 500 showed morphological deformation. Our results suggest that Lipofectamine 2000 is the most suitable transfection medium for gene delivery to NG108-15 and CHO-K1 cells.
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Lípidos , Transfección/métodos , Animales , Células CHO , Línea Celular Tumoral , Cricetinae , Cricetulus , Glioma/genética , Glioma/patología , Humanos , Ratones , Neuroblastoma/genética , Neuroblastoma/patología , RatasRESUMEN
PURPOSE: Image registration is important in functional image analysis. In neurotransmission single photon emission tomography (nSPECT), specific uptake sites can be accurately localized by superimposing the SPECT study onto a high-resolution structural image such as a magnetic resonance (MR) of the subject. Mutual-information (MI)-based algorithms are usually employed for this purpose. Nevertheless, nSPECT/MR registration using MI is often limited by the low count rates present in nSPECT. Several works have proposed extensions of the MI measures to include gradient information (GI) from the images but their performance has not been evaluated in SPECT studies. METHODS: In this work, the accuracy of the MI including gradient information (MIG) was compared with the standard MI using data from healthy volunteers and data simulating a specific uptake reduction using three different radioligands: 123I-IBZM, 123I-ADAM, 123I-R91150. RESULTS: The results showed that MIG-based registration yielded better accuracy than MI. The MIG-based similarity measures were less sensitive to sparse sampling and diminished computational time without a substantial decrease in registration accuracy. CONCLUSIONS: Accuracy of nSPECT/MR registration is improved when gradient information is included in the MI-based algorithm, which makes MIG-based registration potentially useful for clinical applications.
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Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada de Emisión de Fotón Único/métodos , Algoritmos , Benzamidas , Encéfalo/diagnóstico por imagen , Simulación por Computador , Humanos , Teoría de la Información , Radioisótopos de Yodo , Piperidinas , Pirrolidinas , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND: The treatment of malignant melanoma or sarcomas on a limb using extremity perfusion with tumour necrosis factor (TNF-alpha) and melphalan can result in a high degree of systemic toxicity if there is any leakage from the isolated blood territory of the limb into the systemic vascular territory. Leakage is currently controlled by using radiotracers and heavy external probes in a procedure that requires continuous manual calculations. The aim of this work was to develop a light, easily transportable system to monitor limb perfusion leakage by controlling systemic blood pool radioactivity with a portable gamma camera adapted for intraoperative use as an external probe, and to initiate its application in the treatment of MM patients. METHODS: A special collimator was built for maximal sensitivity. Software for acquisition and data processing in real time was developed. After testing the adequacy of the system, it was used to monitor limb perfusion leakage in 16 patients with malignant melanoma to be treated with perfusion of TNF-alpha and melphalan. RESULTS: The field of view of the detector system was 13.8 cm, which is appropriate for the monitoring, since the area to be controlled was the precordial zone. The sensitivity of the system was 257 cps/MBq. When the percentage of leakage reaches 10% the associated absolute error is +/-1%. After a mean follow-up period of 12 months, no patients have shown any significant or lasting side-effects. Partial or complete remission of lesions was seen in 9 out of 16 patients (56%) after HILP with TNF-alpha and melphalan. CONCLUSION: The detector system together with specially developed software provides a suitable automatic continuous monitoring system of any leakage that may occur during limb perfusion. This technique has been successfully implemented in patients for whom perfusion with TNF-alpha and melphalan has been indicated.
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Extremidades/cirugía , Melanoma/diagnóstico por imagen , Sarcoma/diagnóstico por imagen , Supervivencia sin Enfermedad , Diseño de Equipo , Extremidades/diagnóstico por imagen , Cámaras gamma , Humanos , Melanoma/mortalidad , Melanoma/patología , Melanoma/cirugía , Melfalán/uso terapéutico , Monitoreo Intraoperatorio/métodos , Metástasis de la Neoplasia , Cintigrafía , Reproducibilidad de los Resultados , Sarcoma/mortalidad , Sarcoma/patología , Sarcoma/cirugía , Análisis de Supervivencia , Tecnecio , Factor de Necrosis Tumoral alfa/uso terapéuticoRESUMEN
Fingolimod is one of the few oral drugs available for the treatment of multiple sclerosis (MS), a chronic, inflammatory, demyelinating and neurodegenerative disease. The mechanism of action proposed for this drug is based in the phosphorylation of the molecule to produce its active metabolite fingolimod phosphate (FP) which, in turns, through its interaction with S1P receptors, triggers the functional sequestration of T lymphocytes in lymphoid nodes. On the other hand, part if not most of the damage produced in MS and other neurological disorders seem to be mediated by reactive oxygen species (ROS), and mitochondria is one of the main sources of ROS. In the present work, we have evaluated the anti-oxidant profile of FP in a model of mitochondrial oxidative damage induced by menadione (Vitk3) on neuronal cultures. We provide evidence that incubation of neuronal cells with FP alleviates the Vitk3-induced toxicity, due to a decrease in mitochondrial ROS production. It also decreases regulated cell death triggered by imbalance in oxidative stress (restore values of advanced oxidation protein products and total thiol levels). Also restores mitochondrial function (cytochrome c oxidase activity, mitochondrial membrane potential and oxygen consumption rate) and morphology. Furthermore, increases the expression and activity of protective factors (increases Nrf2, HO1 and Trx2 expression and GST and NQO1 activity), being some of these effects modulated by its interaction with the S1P receptor. FP seems to increase mitochondrial stability and restore mitochondrial dynamics under conditions of oxidative stress, making this drug a potential candidate for the treatment of neurodegenerative diseases other than MS.
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Antioxidantes/farmacología , Neuronas Dopaminérgicas/metabolismo , Clorhidrato de Fingolimod/farmacología , Mitocondrias/metabolismo , Esclerosis Múltiple/tratamiento farmacológico , Receptores de Esfingosina-1-Fosfato/metabolismo , Animales , Muerte Celular , Línea Celular , Neuronas Dopaminérgicas/patología , Clorhidrato de Fingolimod/química , Clorhidrato de Fingolimod/uso terapéutico , Humanos , Lisofosfolípidos/metabolismo , Potencial de la Membrana Mitocondrial , Ratones , Imitación Molecular , Neuroprotección , Estrés Oxidativo/efectos de los fármacos , Consumo de Oxígeno , Fosfatos/química , Especies Reactivas de Oxígeno/metabolismo , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Vitamina K 3/toxicidadRESUMEN
OBJECTIVE: Standardised uptake value (SUV) and volumetric parameters such as metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from 18F-FDG PET/CT are useful criteria for disease prognosis in pre-operative and post-treatment epithelial ovarian cancer (EOC). Ki67 is another prognostic biomarker in EOC, associated with tumour aggressiveness. The aim of this study is to evaluate the association between 18F-FDG PET/CT measurements and Ki67 in pre-treatment EOC to determine if PET/CT parameters could non-invasively predict tumour aggressiveness. MATERIAL AND METHODS: A pre-treatment PET/CT was performed on 18 patients with suspected or newly diagnosed EOC. Maximum SUV (SUVmax), mean SUV (SUVmean), whole-body MTV (wbMTV), and whole-body TLG (wbTLG) with a threshold of 30% and 40% of the SUVmax were obtained. Furthermore, Ki67 index (mean and hotspot) was estimated in tumour tissue specimens. Immunohistochemical findings were correlated with PET parameters. RESULTS: The mean age was 57.0 years old (standard deviation 13.6 years). A moderate correlation was observed between mean Ki67 index and SUVmax (r=0.392), SUVmean 30% (r=0.437), and SUVmean 40% (r=0.443), and also between hotspot Ki67 index and SUVmax (r=0.360), SUVmean 30% (r=0.362) and SUVmean 40% (r=0.319). There was a weaker correlation, which was inversely negative, between mean and hotspot Ki67 and volumetric PET parameters. However, no statistical significant differences were found for any correlations. CONCLUSIONS: SUVmax and SUVmean were moderately correlated with Ki67 index, whereas volumetric PET parameters overall, showed a weaker correlation. Thus, SUVmax and SUVmean could be used to assess tumour aggressiveness in pre-treatment EOC.
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Antígenos de Neoplasias/análisis , Carcinoma/diagnóstico por imagen , Radioisótopos de Flúor/farmacocinética , Fluorodesoxiglucosa F18/farmacocinética , Antígeno Ki-67/análisis , Neoplasias Glandulares y Epiteliales/diagnóstico por imagen , Neoplasias Ováricas/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos/farmacocinética , Adulto , Anciano , Carcinoma/metabolismo , Carcinoma Epitelial de Ovario , Simulación por Computador , Femenino , Glucólisis , Humanos , Interpretación de Imagen Asistida por Computador , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Ováricas/metabolismo , Estudios Prospectivos , Distribución Tisular , Carga Tumoral , Adulto JovenRESUMEN
PURPOSE: Human dosimetry studies play a central role in radioligand development for positron emission tomography (PET). Drawing regions of interest (ROIs) on the PET images is used to measure the dose in each organ. In the study aspects related to ROI delineation methods were evaluated for two radioligands of different biodistribution (intestinal vs urinary). PROCEDURES: PET images were simulated from a human voxel-based phantom. Several ROI delineation methods were tested: antero-posterior projections (AP), 3D sub-samples of the organs (S), and a 3D volume covering the whole-organ (W). Inter- and intra-operator variability ROI drawing was evaluated by using human data. RESULTS: The effective dose estimates using S and W methods were comparable to the true values. AP methods overestimated (49 %) the dose for the radioligand with intestinal biodistribution. Moreover, the AP method showed the highest inter-operator variability: 11 ± 1 %. CONCLUSIONS: The sub-sampled organ method showed the best balance between quantitative accuracy and inter- and intra-operator variability.
Asunto(s)
Algoritmos , Procesamiento de Imagen Asistido por Computador , Tomografía de Emisión de Positrones , Radiometría , Simulación por Computador , Humanos , Variaciones Dependientes del Observador , Distribución TisularRESUMEN
Insulin-like growth factor-II (IGF-II) is a naturally occurring hormone that exerts neurotrophic and neuroprotective properties in a wide range of neurodegenerative diseases and ageing. Accumulating evidence suggests that the effects of IGF-II in the brain may be explained by its binding to the specific transmembrane receptor, IGFII/M6P receptor (IGF-IIR). However, relatively little is known regarding the role of IGF-II through IGF-IIR in neuroprotection. Here, using adult cortical neuronal cultures, we investigated whether IGF-II exhibits long-term antioxidant effects and neuroprotection at the synaptic level after oxidative damage induced by high and transient levels of corticosterone (CORT). Furthermore, the involvement of the IGF-IIR was also studied to elucidate its role in the neuroprotective actions of IGF-II. We found that neurons treated with IGF-II after CORT incubation showed reduced oxidative stress damage and recovered antioxidant status (normalized total antioxidant status, lipid hydroperoxides and NAD(P) H:quinone oxidoreductase activity). Similar results were obtained when mitochondria function was analysed (cytochrome c oxidase activity, mitochondrial membrane potential and subcellular mitochondrial distribution). Furthermore, neuronal impairment and degeneration were also assessed (synaptophysin and PSD-95 expression, presynaptic function and FluoroJade B® stain). IGF-II was also able to recover the long-lasting neuronal cell damage. Finally, the effects of IGF-II were not blocked by an IGF-IR antagonist, suggesting the involvement of IGF-IIR. Altogether these results suggest that, in or model, IGF-II through IGF-IIR is able to revert the oxidative damage induced by CORT. In accordance with the neuroprotective role of the IGF-II/IGF-IIR reported in our study, pharmacotherapy approaches targeting this pathway may be useful for the treatment of diseases associated with cognitive deficits (i.e., neurodegenerative disorders, depression, etc.).
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Factor II del Crecimiento Similar a la Insulina/farmacología , Plasticidad Neuronal , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo , Animales , Células Cultivadas , Homólogo 4 de la Proteína Discs Large/metabolismo , Complejo IV de Transporte de Electrones/metabolismo , Glucocorticoides/toxicidad , Potencial de la Membrana Mitocondrial , Neuronas/metabolismo , Neuronas/fisiología , Ratas , Receptor IGF Tipo 2/metabolismo , Sinapsis/efectos de los fármacos , Sinapsis/metabolismo , Sinapsis/fisiología , Sinaptofisina/metabolismoRESUMEN
UNLABELLED: Extrapyramidal symptoms and Parkinsonism (PS) are side effects commonly observed with antipsychotic treatment. However, about 24% of never-treated schizophrenic patients may suffer from PS, which contrast with that 1% observed from the general population. 123I-FP-CIT SPECT has probe useful to differentiate degenerative from non-degenerative PS, so it could be interesting using it for establishing the functional state of presynaptic dopamine neurons of these patients. AIM: To determine the dopamine transporter binding (DAT) in a homogeneous group of first-episode schizophrenic patients. METHODS: An open, transversal study. Thirty schizophrenic in-patients and 15 healthy subjects were recruited. Patients were treated with similar doses of risperidone and all subjects were scanned with 123I-FP-CIT. Extrapyramidal symptoms and psychopathological status was assessed by Simpson-Angus, CGI and PANSS. Semi-quantitative analyses of SPECT images were performed using ROIs placed in caudate nucleus, anterior, medium and posterior putamen and occipital cortex. RESULTS: Whole striatum 123I-FP-CIT binding ratio was significantly lower in patients than healthy subjects (t = 2.56, p < 0.014). This was observed in whole putamen (t = 2.66, p < 0.011), anterior (t = 2.35, p < 0.023), medium (t = 2.38, p < 0.022) and posterior putamen (t = 2.09, p < 0.042). No differences were observed in caudate nucleus (t = 1.81, p = 0.076). Females obtained higher binding ratios than males (t = -3.13, p < 0.003). No correlation was observed between 123I-FP-CIT binding ratios and clinical scales. CONCLUSION: In our series, first episode schizophrenic patients treated with risperidone have a decrease striatal DAT binding assessed with 123I-FP-CIT SPECT. This alteration could be related to their own schizophrenia disease or be secondary to the antipsychotic treatment.
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Antipsicóticos/farmacología , Cuerpo Estriado/química , Antagonistas de Dopamina/farmacología , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/análisis , Proteínas del Tejido Nervioso/análisis , Terminales Presinápticos/química , Risperidona/farmacología , Esquizofrenia/tratamiento farmacológico , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Antipsicóticos/efectos adversos , Enfermedades de los Ganglios Basales/inducido químicamente , Enfermedades de los Ganglios Basales/diagnóstico por imagen , Núcleo Caudado/química , Núcleo Caudado/diagnóstico por imagen , Cuerpo Estriado/diagnóstico por imagen , Estudios Transversales , Antagonistas de Dopamina/efectos adversos , Femenino , Humanos , Radioisótopos de Yodo/farmacocinética , Masculino , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/diagnóstico por imagen , Putamen/química , Putamen/diagnóstico por imagen , Radiofármacos/farmacocinética , Risperidona/efectos adversos , Risperidona/uso terapéutico , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/metabolismo , Factores Sexuales , Tropanos/farmacocinéticaRESUMEN
OBJECTIVE: Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from (18)F-FDG PET/CT are emerging prognostic biomarkers in various solid neoplasms. These volumetric parameters and the SUVmax have shown to be useful criteria for disease prognostication in preoperative and post-treatment epithelial ovarian cancer (EOC) patients. The purpose of this study was to evaluate the utility of (18)F-FDG PET/CT measurements to predict survival in patients with recurrent EOC. MATERIAL AND METHODS: Twenty-six patients with EOC who underwent a total of 31 (18)F-FDG PET/CT studies for suspected recurrence were retrospectively included. SUVmax and volumetric parameters whole-body MTV (wbMTV) and whole-body TLG (wbTLG) with a threshold of 40% and 50% of the SUVmax were obtained. Correlation between PET parameters and progression-free survival (PFS) and the survival analysis of prognostic factors were calculated. RESULTS: Serous cancer was the most common histological subtype (76.9%). The median PFS was 12.5 months (range 10.7-20.6 months). Volumetric parameters showed moderate inverse correlation with PFS but there was no significant correlation in the case of SUVmax. The correlation was stronger for first recurrences. By Kaplan-Meier analysis and log-rank test, wbMTV 40%, wbMTV 50% and wbTLG 50% correlated with PFS. However, SUVmax and wbTLG 40% were not statistically significant predictors for PFS. CONCLUSION: Volumetric parameters wbMTV and wbTLG 50% measured by (18)F-FDG PET/CT appear to be useful prognostic predictors of outcome and may provide valuable information to individualize treatment strategies in patients with recurrent EOC.
Asunto(s)
Recurrencia Local de Neoplasia/diagnóstico por imagen , Neoplasias Ováricas/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Femenino , Humanos , Imagen Multimodal , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Tomografía de Emisión de Positrones , Pronóstico , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Carga TumoralRESUMEN
Endogenous interferon beta (IFNß) is an important cytokine involved in several chronic inflammatory diseases, such as Multiple Sclerosis (MS). In spite of the numerous therapeutic approaches available for MS patients, the administration of recombinant IFNß continues being one of the first line treatment to these patients. The soluble form of IFNß receptor (sIFNAR2) could act as critical regulator of the endogenous and the systemically administered IFNß, but whether it functions as an agonist or antagonist of its ligand is not completely elucidated. Morover, the possible role of sIFNAR2 in autoimmune diseases like MS is still unknown and so far overlooked. Here we evaluated the efficacy of the combined therapy of IFNß and our recombinant protein analogous to human sIFNAR2 as a treatment in a chronic mice model of MS (CP-EAE). We also tested the effect of the sIFNAR2 administered as a monotherapy over these EAE-animals. The results showed that our recombinant sIFNAR2 protein potentiates the immunomodulatory effects of exogenous IFNß in CP-EAE by increasing the reduction of the induced inflammation and the tissue damage. Furthermore, we demonstrate for the first time that sIFNAR2 shows intrinsic properties by modulating the CP-EAE progression and the neuroinflammation processes related to this disease. Another intrinsic activity showed by sIFNAR2 is the inhibition of the T cells proliferation, which increase its potential as therapeutic molecule.
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Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Inmunosupresores/administración & dosificación , Receptor de Interferón alfa y beta/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Animales , Proliferación Celular/efectos de los fármacos , Quimioterapia Combinada , Encefalomielitis Autoinmune Experimental/patología , Encefalomielitis Autoinmune Experimental/fisiopatología , Escherichia coli , Femenino , Humanos , Interferón beta/administración & dosificación , Interferón beta/metabolismo , Ratones Endogámicos C57BL , Microglía/efectos de los fármacos , Microglía/patología , Microglía/fisiología , Neuronas/efectos de los fármacos , Neuronas/patología , Neuronas/fisiología , Oligodendroglía/efectos de los fármacos , Oligodendroglía/patología , Oligodendroglía/fisiología , Factor de Transcripción STAT1/metabolismo , Transducción de Señal/efectos de los fármacos , Médula Espinal/efectos de los fármacos , Médula Espinal/patología , Médula Espinal/fisiopatología , Bazo/efectos de los fármacos , Bazo/fisiopatología , Linfocitos T/efectos de los fármacos , Linfocitos T/fisiologíaRESUMEN
The effect of the muscarinic receptors agonist carbachol (Cch) on intracellular calcium concentration ([Ca(2+)](i)) and cAMP level was studied in polarized Fischer rat thyroid (FRT) epithelial cells. Cch provoked a transient increase in [Ca(2+)](i), followed by a lower sustained phase. Thapsigargin, a specific microsomal Ca(2+)-ATPase inhibitor, caused a rapid rise in [Ca(2+)](i) and subsequent addition of Cch was without effect. Removal of extracellular Ca(2+) reduced the initial transient response and completely abolished the plateau phase. Ryanodine, an agent that depletes intracellular Ca(2+) stores through stimulation of ryanodine receptors (RyRs), had no effect on [Ca(2+)](i). However, the transitory activation of [Ca(2+)](i) was dose-dependently attenuated in cells pretreated with U73122, a specific inhibitor of phospholipase C (PLC). These data suggest that the Cch-stimulated increment of [Ca(2+)](i) required IP(3) formation and binding to its specific receptors in Ca(2+) stores. Further studies were performed to investigate whether the effect of Cch on Ca(2+) entry into FRT cells was via L-type voltage-dependent Ca(2+) channels (L-VDCCs). Nicardipine, a nonspecific L-type Ca(2+) channel blocker, decreased Cch-induced increase on [Ca(2+)](i), while Bay K-8644, an L-type Ca(2+) channel agonist, slightly increased [Ca(2+)](i) in FRT cells. These data indicate that Ca(2+) entry into these nondifferentiated thyroid cells occurs through an L-VDCC, and probably through another mechanism such as a capacitative pathway. Cch did not affect the intracellular cAMP levels, but its effects on [Ca(2+)](i) were significantly reduced when cells were pretreated with forskolin, suggesting the existence of an intracellular cross-talk between PLC and cAMP mechanisms in the regulation of intracellular Ca(2+) mobilization in neoplastic FRT cells.
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Calcio/metabolismo , Carbacol/farmacología , AMP Cíclico/metabolismo , Inhibidores Enzimáticos/farmacología , Agonistas Muscarínicos/farmacología , Antagonistas Muscarínicos/farmacología , Receptores Muscarínicos/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Canales de Calcio Tipo L/efectos de los fármacos , Canales de Calcio Tipo L/metabolismo , Carbacol/metabolismo , Línea Celular , Colforsina/farmacología , Relación Dosis-Respuesta a Droga , Activación Enzimática , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Ratas , Ratas Endogámicas F344 , Rianodina/farmacología , Transducción de Señal , Glándula Tiroides , Factores de TiempoRESUMEN
Water skiing, boat racing, skin and scuba diving, as well as pleasure boat cruising are becoming increasingly popular hobbies. As a result, the incidence of injuries secondary to motor propellers is becoming more frequent. Injuries by propellers, amputation, death by drowning, and bleeding are rare reported events in forensic literature. The most common circumstances surrounding boat-propeller-related injuries are concerned with getting into or out of the boat, personal watercraft use or water skiing, and falling or being thrown from the boat. A case of a scuba diver's death that occurred during an illegal scuba fishing trip around a desalination plant is presented. A complete autopsy and histological study of all organs and surfaces of dismembered cadaveric sections, performed in order to determine the phases of death, are reported. An underwater scene investigation was conducted by an engineering team studying the mouth of the pump and the dynamic characteristic of rotating propeller blades.
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Amputación Traumática/etiología , Muerte , Buceo , Medicina Legal , Purificación del Agua , Humanos , Masculino , Persona de Mediana Edad , Heridas y LesionesRESUMEN
The aim of this work was to evaluate the influence of anatomical variability between subjects and of the partial volume effect (PVE) on the standardized Specific Uptake Ratio (SUR) in [(123)I]FP-bib SPECT studies. To this end, magnetic resonance (MR) images of 23 subjects with differences in the striatal volume of up to 44% were segmented and used to generate a database of 138 Monte Carlo simulated SPECT studies. Data included normal uptakes and pathological cases. Studies were reconstructed by filtered back projection (FBP) and the ordered-subset expectation-maximization algorithm. Quantification was carried out by applying a reference method based on regions of interest (ROIs) derived from the MR images and ROIs derived from the Automated Anatomical Labelling map. Our results showed that, regardless of anatomical variability, the relationship between calculated and true SUR values for caudate and putamen could be described by a multiple linear model which took into account the spill-over phenomenon caused by PVE (R² ≥ 0.963 for caudate and ≥0.980 for putamen) and also by a simple linear model (R(2) ≥ 0.952 for caudate and ≥0.973 for putamen). Calculated values were standardized by inverting both linear systems. Differences between standardized and true values showed that, although the multiple linear model was the best approach in terms of variability (X² ≥ 11.79 for caudate and ≤7.36 for putamen), standardization based on a simple linear model was also suitable (X² ≥ 12.44 for caudate and ≤12.57 for putamen).
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Algoritmos , Radiofármacos/farmacocinética , Tomografía Computarizada de Emisión de Fotón Único/métodos , Interpretación Estadística de Datos , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Humanos , Radioisótopos de Yodo/farmacocinética , Método de Montecarlo , Neostriado/diagnóstico por imagen , Tropanos/farmacocinéticaRESUMEN
In this work a comparison between experimental and simulated data using GATE and PeneloPET Monte Carlo simulation packages is presented. All simulated setups, as well as the experimental measurements, followed exactly the guidelines of the NEMA NU 4-2008 standards using the microPET R4 scanner. The comparison was focused on spatial resolution, sensitivity, scatter fraction and counting rates performance. Both GATE and PeneloPET showed reasonable agreement for the spatial resolution when compared to experimental measurements, although they lead to slight underestimations for the points close to the edge. High accuracy was obtained between experiments and simulations of the system's sensitivity and scatter fraction for an energy window of 350-650 keV, as well as for the counting rate simulations. The latter was the most complicated test to perform since each code demands different specifications for the characterization of the system's dead time. Although simulated and experimental results were in excellent agreement for both simulation codes, PeneloPET demanded more information about the behavior of the real data acquisition system. To our knowledge, this constitutes the first validation of these Monte Carlo codes for the full NEMA NU 4-2008 standards for small animal PET imaging systems.