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Introduction: Synapses and spines play a significant role in major depressive disorder (MDD) pathophysiology, recently highlighted by the rapid antidepressant effect of ketamine and psilocybin. According to the Bayesian brain and interoception perspectives, MDD is formalized as being stuck in affective states constantly predicting negative energy balance. To understand how spines and synapses relate to the predictive function of the neocortex and thus to symptoms, we used the temporal memory (TM), an unsupervised machine-learning algorithm. TM models a single neocortical layer, learns in real-time, and extracts and predicts temporal sequences. TM exhibits neocortical biological features such as sparse firing and continuous online learning using local Hebbian-learning rules. Methods: We trained a TM model on random sequences of upper-case alphabetical letters, representing sequences of affective states. To model depression, we progressively destroyed synapses in the TM model and examined how that affected the predictive capacity of the network. We found that the number of predictions decreased non-linearly. Results: Destroying 50% of the synapses slightly reduced the number of predictions, followed by a marked drop with further destruction. However, reducing the synapses by 25% distinctly dropped the confidence in the predictions. Therefore, even though the network was making accurate predictions, the network was no longer confident about these predictions. Discussion: These findings explain how interoceptive cortices could be stuck in limited affective states with high prediction error. Connecting ketamine and psilocybin's proposed mechanism of action to depression pathophysiology, the growth of new synapses would allow representing more futuristic predictions with higher confidence. To our knowledge, this is the first study to use the TM model to connect changes happening at synaptic levels to the Bayesian formulation of psychiatric symptomatology. Linking neurobiological abnormalities to symptoms will allow us to understand the mechanisms of treatments and possibly, develop new ones.

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Computer-aided diagnosis (CAD) systems can be used to process breast ultrasound (BUS) images with the goal of enhancing the capability of diagnosing breast cancer. Many CAD systems operate by analyzing the region-of-interest (ROI) that contains the tumor in the BUS image using conventional texture-based classification models and deep learning-based classification models. Hence, the development of these systems requires automatic methods to localize the ROI that contains the tumor in the BUS image. Deep learning object-detection models can be used to localize the ROI that contains the tumor, but the ROI generated by one model might be better than the ROIs generated by other models. In this study, a new method, called the edge-based selection method, is proposed to analyze the ROIs generated by different deep learning object-detection models with the goal of selecting the ROI that improves the localization of the tumor region. The proposed method employs edge maps computed for BUS images using the recently introduced Dense Extreme Inception Network (DexiNed) deep learning edge-detection model. To the best of our knowledge, our study is the first study that has employed a deep learning edge-detection model to detect the tumor edges in BUS images. The proposed edge-based selection method is applied to analyze the ROIs generated by four deep learning object-detection models. The performance of the proposed edge-based selection method and the four deep learning object-detection models is evaluated using two BUS image datasets. The first dataset, which is used to perform cross-validation evaluation analysis, is a private dataset that includes 380 BUS images. The second dataset, which is used to perform generalization evaluation analysis, is a public dataset that includes 630 BUS images. For both the cross-validation evaluation analysis and the generalization evaluation analysis, the proposed method obtained the overall ROI detection rate, mean precision, mean recall, and mean F1-score values of 98%, 0.91, 0.90, and 0.90, respectively. Moreover, the results show that the proposed edge-based selection method outperformed the four deep learning object-detection models as well as three baseline-combining methods that can be used to combine the ROIs generated by the four deep learning object-detection models. These findings suggest the potential of employing our proposed method to analyze the ROIs generated using different deep learning object-detection models to select the ROI that improves the localization of the tumor region.

Asunto(s)

Neoplasias de la Mama , Aprendizaje Profundo , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Diagnóstico por Computador , Femenino , Humanos , Ultrasonografía Mamaria/métodos

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BACKGROUND: Ultrasound is employed in needle interventions to visualize the anatomical structures and track the needle. Nevertheless, needle detection in ultrasound images is a difficult task, specifically at steep insertion angles. PURPOSE: A new method is presented to enable effective needle detection using ultrasound B-mode and power Doppler analyses. METHODS: A small buzzer is used to excite the needle and an ultrasound system is utilized to acquire B-mode and power Doppler images for the needle. The B-mode and power Doppler images are processed using Radon transform and local-phase analysis to initially detect the axis of the needle. The detection of the needle axis is improved by processing the power Doppler image using alpha shape analysis to define a region of interest (ROI) that contains the needle. Also, a set of feature maps is extracted from the ROI in the B-mode image. The feature maps are processed using a machine learning classifier to construct a likelihood image that visualizes the posterior needle likelihoods of the pixels. Radon transform is applied to the likelihood image to achieve an improved needle axis detection. Additionally, the region in the B-mode image surrounding the needle axis is analyzed to identify the needle tip using a custom-made probabilistic approach. Our method was utilized to detect needles inserted in ex vivo animal tissues at shallow [ 20 ∘ - 40 ∘ $20^\circ -40^\circ$ ), moderate [ 40 ∘ - 60 ∘ $40^\circ -60^\circ$ ), and steep [ 60 ∘ - 85 ∘ $60^\circ -85^\circ$ ] angles. RESULTS: Our method detected the needles with failure rates equal to 0% and mean angle, axis, and tip errors less than or equal to 0.7°, 0.6 mm, and 0.7 mm, respectively. Additionally, our method achieved favorable results compared to two recently introduced needle detection methods. CONCLUSIONS: The results indicate the potential of applying our method to achieve effective needle detection in ultrasound images.

Asunto(s)

Agujas , Radón , Animales , Ultrasonografía/métodos , Ultrasonografía Doppler , Ultrasonografía Intervencional

RESUMEN

<b>Background and Objective:</b> <i>Moringa peregrina</i> (family Moringaceae) is a common flowering plant found in the Arabian Peninsula, Horn of Africa and Southern Sinai, Egypt. The purpose of this study was to investigate the protective activity of MP-SeNPs against BaP-induced mammal tissue injury in rats. <b>Materials and Methods:</b> MP-SeNPs were prepared and characterized in terms of particle size and zeta potential. Furthermore, the IC₅₀ of MP-SeNPs against the Mcf7 breast carcinoma cell line and LD₅₀ was evaluated. Adult albino rats weighing approximately 187±10 g was used to assess the lung protective activity of MP-SeNPs (28.7 and 71.75 mg kg¹ b.wt.) against BaP-induced mammal tissue injury in rats. <b>Results:</b> The mean particle size of MP-SeNPs was 134.69±8.24 nm with negative zeta potential of +26.04 with the observed shapes of nano particle was spherical. Also, IC₅₀ of MP-SeNPs against Mcf7 breast carcinoma cell line = 89.57 µg mL¹ and LD₅₀ equals and 1435 mg kg¹ b.wt., respectively. The daily oral administration of MP-SeNPs at concentrations of 28.7 and 71.75 mg kg¹ b.wt. for 30 days to rats treated with BaP (20 mg kg¹ b.wt.) resulted in a significant improvement of IL-2, IL-6 and IL-10. Oral administration of MP-SeNPs, on the other hand, increased the levels of SOD, GPx, TNF-α, iNOs and GSH as well as decreased the level of MDA in mammal tissue of BaP-treated rats. Furthermore, MP-SeNPs almost normalized these effects in mammal tissue histoarchitecture and MRI examination. <b>Conclusion:</b> The biochemical, histological and MRI findings incurrent study demonstrated that MP-SeNPs have protective activity against BaP-induced mammal tissue injury in rats.

Asunto(s)

Antioxidantes/farmacología , Benzo(a)pireno/farmacología , Estrés Oxidativo/efectos de los fármacos , Administración Oral , Animales , Antineoplásicos/química , Emulsiones , Femenino , Humanos , Pulmón/efectos de los fármacos , Células MCF-7 , Imagen por Resonancia Magnética , Moringa , Nanopartículas/química , Fitoquímicos , Ratas , Especies Reactivas de Oxígeno , Temperatura , Sales de Tetrazolio/química , Tiazoles/química , Factor de Necrosis Tumoral alfa/metabolismo , Difracción de Rayos X

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Long term mortality is higher in Non-ST-segment elevated myocardial infarction (NSTEMI) patients than STEMI paitents. NSTEMI are a high risk factor for ensuing cardiovascular events in diabetic patients. But, use of drug eluting stents (DES) will further improve outcomes in patients with diabetes suffering early percutaneous coronary intervention (PCI). The aim of the study was to determine the changes in left ventricular (LV) systolic activity after successful PCI in NSTEMI diabetic patients was compared with non-diabetic patients. This comparative clinical study was performed in the Department of Cardiology, University Cardiac Center, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2017 to June 2018. Thirty (30) diabetic and 34 non-diabetic patients with NSTEMI undergoing percutaneous coronary intervention were included in the study. In all patients PCI with drug eluting stent was performed successfully. Earlier echocardiography (2-Dimensional) was done, at release subsequent PCI and 3 months afterward to evaluate the LV systolic activity and compare to diabetics and non-diabetics at all levels of evaluation to assess the outcome of intervention. At baseline LVEF was rather lower in diabetic group than non-diabetic group patients. In diabetics patients segments with abnormal wall motion (WMA) was higher than non-diabetics patients. While the LVEDD, LVIDd and LVIDs were significantly larger in the earlier group than those in the latter group, the LVESV was no different in both groups. At release from hospital, no significant enhancement was observed in either group following PCI in terms of LVEF, number of segments with WMA, LVIDd and LVIDs. However, both LVEDV and LVESV reduced successfully in both groups with decrease of LVESV being more marked in non-diabetics compared with diabetics (p=0.018). However, 3 months after PCI, LVEF improved (8.4±1.2%) in diabetics and 7.9±1.2% in non diabetics patients but this improvement between two groups was not statically significant (p=0.631). Similarly baseline to 3 months after PCI LVIDs reduces in diabetics patients (5.7±1.9%) and 4.8±1.1% in non diabetics patients but the difference between both groups was not significant (p=0.201). Diabetic patients more frequently required 2 stents (p=0.30), while stent's diameter and length did not differ between the study groups. This study demonstrated that improvement of the parameters of left ventricular systolic function after using of drug eluting stent in NSTEMI diabetic patients was not lower to the non diabetic group under same condition. So, suggestion of PCI with drug eluting stent may be extended in NSTEMI diabetic patient.

Asunto(s)

Diabetes Mellitus , Stents Liberadores de Fármacos , Infarto del Miocardio , Infarto del Miocardio sin Elevación del ST , Intervención Coronaria Percutánea , Bangladesh , Humanos , Resultado del Tratamiento

RESUMEN

Game-based rehabilitation systems provide an effective tool to engage cerebral palsy patients in physical exercises within an exciting and entertaining environment. A crucial factor to ensure the effectiveness of game-based rehabilitation systems is to assess the correctness of the movements performed by the patient during the game-playing sessions. In this study, we propose a game-based rehabilitation system for upper-limb cerebral palsy that includes three game-based exercises and a computerized assessment method. The game-based exercises aim to engage the participant in shoulder flexion, shoulder horizontal abduction/adduction, and shoulder adduction physical exercises that target the right arm. Human interaction with the game-based rehabilitation system is achieved using a Kinect sensor that tracks the skeleton joints of the participant. The computerized assessment method aims to assess the correctness of the right arm movements during each game-playing session by analyzing the tracking data acquired by the Kinect sensor. To evaluate the performance of the computerized assessment method, two groups of participants volunteered to participate in the game-based exercises. The first group included six cerebral palsy children and the second group included twenty typically developing subjects. For every participant, the computerized assessment method was employed to assess the correctness of the right arm movements in each game-playing session and these computer-based assessments were compared with matching gold standard evaluations provided by an experienced physiotherapist. The results reported in this study suggest the feasibility of employing the computerized assessment method to evaluate the correctness of the right arm movements during the game-playing sessions.

Asunto(s)

Parálisis Cerebral/terapia , Rehabilitación de Accidente Cerebrovascular/métodos , Niño , Preescolar , Terapia por Ejercicio/métodos , Femenino , Humanos , Articulaciones/fisiología , Masculino , Hombro/fisiología , Esqueleto/fisiología , Extremidad Superior/fisiología

RESUMEN

BACKGROUND: Manual noninvasive respiratory techniques have traditionally been used to treat respiratory pathologies. The aim of this study was to analyze the effects of the diaphragmatic release technique and the thoracic lymphatic pump technique versus conventional respiratory retraining in children with asthma. METHODS: Using a quasi-experimental design, 60 children with asthma were allocated to undergo the diaphragmatic release technique (n = 20), thoracic lymphatic pump technique (n = 20), or conventional respiratory retraining (n = 20) in this study. Serum immunoglobulin E levels, diaphragmatic mobility, pulmonary function, and P(A-a)O2 were assessed before and after 12 treatment sessions that were conducted over nonconsecutive days in a 4-week program. RESULTS: After 12 treatments, the changes in the serum immunoglobulin E level for each group was not significantly different from the other groups. Compared with conventional respiratory retraining, the diaphragmatic release technique was associated with a significant improvement in FVC (P = .001) and FEV1 (P = .002); the thoracic lymphatic pump technique showed no differences. With regard to diaphragmatic mobility, both the diaphragmatic release technique and the thoracic lymphatic pump technique yielded significantly favorable effects when compared with conventional respiratory retraining (P < .001 and P = .01, respectively). Further, no significant between-group differences were detected in terms of the P(A-a)O2 (P = .07). CONCLUSIONS: The thoracic lymphatic pump technique and conventional respiratory retraining approaches were helpful interventions that could be used to alleviate the symptoms of childhood asthma. Nevertheless, the diaphragmatic release technique was a potentially more effective intervention.

Asunto(s)

Asma , Diafragma/fisiopatología , Manipulaciones Musculoesqueléticas/métodos , Terapia Respiratoria/métodos , Asma/fisiopatología , Asma/terapia , Ejercicios Respiratorios , Niño , Investigación sobre la Eficacia Comparativa , Femenino , Humanos , Masculino , Respiración , Mecánica Respiratoria/fisiología , Resultado del Tratamiento

RESUMEN

Developing efficient evolutionary algorithms attracts many researchers due to the existence of optimization problems in numerous real-world applications. A new differential evolution algorithm, sTDE-dR, is proposed to improve the search quality, avoid premature convergence, and stagnation. The population is clustered in multiple tribes and utilizes an ensemble of different mutation and crossover strategies. In this algorithm, a competitive success-based scheme is introduced to determine the life cycle of each tribe and its participation ratio for the next generation. In each tribe, a different adaptive scheme is used to control the scaling factor and crossover rate. The mean success of each subgroup is used to calculate the ratio of its participation for the next generation. This guarantees that successful tribes with the best adaptive schemes are only the ones that guide the search toward the optimal solution. The population size is dynamically reduced using a dynamic reduction method. Comprehensive comparison of the proposed heuristic over a challenging set of benchmarks from the CEC2014 real parameter single objective competition against several state-of-the-art algorithms is performed. The results affirm robustness of the proposed approach compared to other state-of-the-art algorithms.

RESUMEN

Peroxisome proliferator-activated receptors (PPARs) are members of the steroid hormone receptor superfamily, discovered in 1990. To date, three PPAR subtypes have been identified; PPARα, PPAR ß/δ, and PPARγ. These receptors share a high degree of homology but differ in tissue distribution and ligand specificity. PPARs have been implicated in the etiology as well as treatment of several important diseases and pathological conditions such as diabetes, inflammation, senescence-related diseases, regulation of fertility, and various types of cancer. Consequently, significant efforts to discover novel PPAR roles and delineate molecular mechanisms involved in their activation and repression as well as develop safer and more effective PPAR modulators, as therapeutic agents to treat a myriad of diseases and conditions, are underway. This volume of Methods in Molecular Biology contains details of experimental protocols used in researching these receptors.

Asunto(s)

Receptores Activados del Proliferador del Peroxisoma , Animales , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Receptores Activados del Proliferador del Peroxisoma/química , Receptores Activados del Proliferador del Peroxisoma/historia , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Investigación

RESUMEN

BACKGROUND: Changes in immune function believed to contribute to a variety of age-related diseases have been associated with increased production of nitric oxide (NO). We have recently reported that proteasome inhibitors (dexamethasone, mevinolin, quercetin, δ-tocotrienol, and riboflavin) can inhibit lipopolysaccharide (LPS)-induced NO production in vitro by RAW 264.7 cells and by thioglycolate-elicited peritoneal macrophages derived from four strains of mice (C57BL/6, BALB/c, LMP7/MECL-1(-/-) and PPAR-α(-/-) knockout mice). The present study was carried out in order to further explore the potential effects of diet supplementation with naturally-occurring inhibitors (δ-tocotrienol and quercetin) on LPS-stimulated production of NO, TNF-α, and other pro-inflammatory cytokines involved in the ageing process. Young (4-week-old) and senescent mice (42-week old) were fed control diet with or without quercetin (100 ppm), δ-tocotrienol (100 ppm), or dexamethasone (10 ppm; included as positive control for suppression of inflammation) for 4 weeks. At the end of feeding period, thioglycolate-elicited peritoneal macrophages were collected, stimulated with LPS, LPS plus interferon-ß (IFN-ß), or LPS plus interferon-γ (IFN-γ), and inflammatory responses assessed as measured by production of NO and TNF-α, mRNA reduction for TNF-α, and iNOS genes, and microarray analysis. RESULTS: Thioglycolate-elicited peritoneal macrophages prepared after four weeks of feeding, and then challenged with LPS (10 ng or 100 ng) resulted in increases of 55% and 73%, respectively in the production of NO of 46-week-old compared to 8-week-old mice fed control diet alone (respective control groups), without affecting the secretion of TNF-α among these two groups. However, macrophages obtained after feeding with quercetin, δ-tocotrienol, and dexamethasone significantly inhibited (30% to 60%; P < 0.02) the LPS-stimulated NO production, compared to respective control groups. There was a 2-fold increase in the production of NO, when LPS-stimulated macrophages of quercetin, δ-tocotrienol, or dexamethasone were also treated with IFN-ß or IFN-γ compared to respective control groups. We also demonstrated that NO levels and iNOS mRNA expression levels were significantly higher in LPS-stimulated macrophages from senescent (0.69 vs 0.41; P < 0.05), compared to young mice. In contrast, age did not appear to impact levels of TNF-α protein or mRNA expression levels (0.38 vs 0.35) in LPS-stimulated macrophages. The histological analyses of livers of control groups showed lesions of peliosis and microvesicular steatosis, and treated groups showed Councilman body, and small or large lymphoplasmacytic clusters. CONCLUSIONS: The present results demonstrated that quercetin and δ-tocotrienols inhibit the LPS-induced NO production in vivo. The microarray DNA analyses, followed by pathway analyses indicated that quercetin or δ-tocotrienol inhibit several LPS-induced expression of several ageing and pro-inflammatory genes (IL-1ß, IL-1α, IL-6, TNF-α, IL-12, iNOS, VCAM1, ICAM1, COX2, IL-1RA, TRAF1 and CD40). The NF-κB pathway regulates the production of NO and inhibits the pro-inflammatory cytokines involved in normal and ageing process. These ex vivo results confirmed the earlier in vitro findings. The present findings of inhibition of NO production by quercetin and δ-tocotrienol may be of clinical significance treating several inflammatory diseases, including ageing process.

Asunto(s)

Antiinflamatorios/farmacología , Macrófagos Peritoneales/metabolismo , Quercetina/farmacología , Vitamina E/análogos & derivados , Factores de Edad , Animales , Antiinflamatorios/uso terapéutico , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Dexametasona/farmacología , Suplementos Dietéticos , Perfilación de la Expresión Génica , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Interferón beta/farmacología , Interferón gamma/farmacología , Lipopolisacáridos/farmacología , Hígado/efectos de los fármacos , Hígado/inmunología , Hígado/patología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Quercetina/uso terapéutico , Transcripción Genética/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Vitamina E/farmacología , Vitamina E/uso terapéutico , Aumento de Peso/efectos de los fármacos

RESUMEN

BACKGROUND: Inflammation has been implicated in a variety of diseases associated with ageing, including cancer, cardiovascular, and neurologic diseases. We have recently established that the proteasome is a pivotal regulator of inflammation, which modulates the induction of inflammatory mediators such as TNF-α, IL-1, IL-6, and nitric oxide (NO) in response to a variety of stimuli. The present study was undertaken to identify non-toxic proteasome inhibitors with the expectation that these compounds could potentially suppress the production of inflammatory mediators in ageing humans, thereby decreasing the risk of developing ageing related diseases. We evaluated the capacity of various proteasome inhibitors to suppress TNF-α, NO and gene suppression of TNF-α, and iNOS mRNA, by LPS-stimulated macrophages from several sources. Further, we evaluated the mechanisms by which these agents suppress secretion of TNF-α, and NO production. Over the course of these studies, we measured the effects of various proteasome inhibitors on the RAW 264.7 cells, and peritoneal macrophages from four different strains of mice (C57BL/6, BALB/c, proteasome double subunits knockout LMP7/MECL-1-/-, and peroxisome proliferator-activated receptor-α,-/- (PPAR-α,-/-) knockout mice. We also directly measured the effect of these proteasome inhibitors on proteolytic activity of 20S rabbit muscle proteasomes. RESULTS: There was significant reduction of chymotrypsin-like activity of the 20S rabbit muscle proteasomes with dexamethasone (31%), mevinolin (19%), δ-tocotrienol (28%), riboflavin (34%), and quercetin (45%; P < 0.05). Moreover, quercetin, riboflavin, and δ-tocotrienol also inhibited chymotrypsin-like, trypsin-like and post-glutamase activities in RAW 264.7 whole cells. These compounds also inhibited LPS-stimulated NO production and TNF-α, secretion, blocked the degradation of P-IκB protein, and decreased activation of NF-κB, in RAW 264.7 cells. All proteasome inhibitors tested also significantly inhibited NO production (30% to 60% reduction) by LPS-induced thioglycolate-elicited peritoneal macrophages derived from all four strains of mice. All five compounds also suppressed LPS-induced TNF-α, secretion by macrophages from C57BL/6 and BALB/c mice. TNF-α, secretion, however, was not suppressed by any of the three proteasome inhibitors tested (δ-tocotrienol, riboflavin, and quercetin) with LPS-induced macrophages from LMP7/MECL-1-/- and PPAR-α,-/- knockout mice. Results of gene expression studies for TNF-α, and iNOS were generally consistent with results obtained for TNF-α, protein and NO production observed with four strains of mice. CONCLUSIONS: Results of the current study demonstrate that δ-tocotrienol, riboflavin, and quercetin inhibit NO production by LPS-stimulated macrophages of all four strains of mice, and TNF-α, secretion only by LPS-stimulated macrophages of C57BL/6 and BALB/c mice. The mechanism for this inhibition appears to be decreased proteolytic degradation of P-IκB protein by the inhibited proteasome, resulting in decreased translocation of activated NF-κB to the nucleus, and depressed transcription of gene expression of TNF-α, and iNOS. Further, these naturally-occurring proteasome inhibitors tested appear to be relatively potent inhibitors of multiple proteasome subunits in inflammatory proteasomes. Consequently, these agents could potentially suppress the production of inflammatory mediators in ageing humans, thereby decreasing the risk of developing a variety of ageing related diseases.

Asunto(s)

Antiinflamatorios no Esteroideos/farmacología , Citocinas/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Óxido Nítrico/metabolismo , Inhibidores de Proteasoma , Animales , Línea Celular Transformada , Cisteína Endopeptidasas/genética , Citocinas/antagonistas & inhibidores , Citocinas/genética , Femenino , Proteínas I-kappa B/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Músculos/metabolismo , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , PPAR alfa/genética , Complejo de la Endopetidasa Proteasomal/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , ARN Mensajero/metabolismo , Conejos

RESUMEN

OBJECTIVE: Cervical meningoceles are rare. Clinical, radiological and surgical data of 8 cases were presented, including a unique case of double cervical and lumbosacral meningoceles. METHODS: This retrospective study included all children operated on for cervical meningocele from January 2004 to June 2009 at the Aburish Pediatric Hospital, Cairo University. RESULTS: Eight children (6 boys and 2 girls) were operated on. Their ages ranged between 2 months and 8 years. The clinical picture--apart form posterior cervical swelling--was almost normal. One case had paraplegia due to associated lumbosacral myelomeningocele (double meningocele). Four patients had associated hydrocephalus; 2 had Chiari malformation and 2 hydromyelia. CONCLUSION: The outcome after surgery for these lesions is excellent as the majority of the children have no or minimal neurological deficit and surgery does help in improving cosmesis and preventing the development of neurological deterioration.

Asunto(s)

Meningocele/diagnóstico por imagen , Meningocele/cirugía , Disrafia Espinal/diagnóstico por imagen , Disrafia Espinal/cirugía , Malformación de Arnold-Chiari/complicaciones , Vértebras Cervicales , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Hidrocefalia/etiología , Lactante , Vértebras Lumbares , Masculino , Meningocele/complicaciones , Paraplejía/etiología , Radiografía , Estudios Retrospectivos , Sacro , Disrafia Espinal/complicaciones

RESUMEN

OBJECTIVE: To compare the anti-hypertensive effects of both remifentanil and esmolol infusion. METHODS: This prospective comparative study was conducted on 20 patients (10 patients in each group), in the Neurosurgical Theater of Kasr Elaini Hospital, Cairo, Egypt from 2006 to 2008. The patients were divided into 2 equal groups. In group one, remifentanil was used as a bolus of one ug/kg intravenous (iv) in 30-60 seconds, followed by infusion at a rate of 0.25-0.5 ug/kg/min until the systolic blood pressure was <140 mm Hg. In group 2, esmolol was given as a 500 ug/kg iv bolus in 30 seconds followed by continued infusion of 100-300 ug/kg/min until systolic blood pressure was <140 mm Hg. Infusion was continued until the patients left the post anesthesia care unit (PACU). RESULTS: The onset time of decreasing blood pressure was shorter in group 2 (40+/-0.01 seconds) than group one (52.5+/-4.47 seconds). The PACU and hospital stay were comparable between both groups. CONCLUSION: Remifentanil can be used to control blood pressure during emergence of anesthesia after craniotomy for brain tumors. It has higher rapid recovery score than esmolol and other narcotics. In addition, it can be used when esmolol is contraindicated such as in cardiac patients, asthmatics, chronic obstructive pulmonary disease, or during pregnancy. Also, it decreases the need for postoperative analgesia and allows sedation if the infusion is continued as surgical patients are admitted to the ICU.

RESUMEN

OBJECTIVE: To compare awake craniotomy using conscious sedation technique versus conventional general anesthesia (GA) for excision of low-grade glioma encroaching on eloquent brain. METHODS: This prospective study included 40 patients ASA classification 1 and 2, aged 23-55 years, harboring low-grade glioma encroaching on eloquent brain. The study was carried out in the Neurosurgical Theatre in Kasr El-Aini Hospital, Cairo, Egypt, from January 2007 to November 2008. Twenty patients (group 1) received GA with endotracheal intubation and controlled ventilation. In group 2, awake craniotomy was carried out using local anesthetic infiltration, and intravenous injection of propofol and fentanyl. RESULTS: Forty patients completed the study. In the awake group, none of the patients received GA, 2 patients developed intraoperative agitation, 5 patients were over-sedated, and none of the awake patients developed intraoperative nausea or vomiting. Four patients in the GA group developed post-operative nausea and vomiting compared to one patient in the awake group, and this difference was statistically significant (p=0.039). The neurological outcome regarding motor power and/or speech was found better or with no fresh deficits, immediately postoperative in 90% of the awake group patients. This is compared to 40% in the GA group. The difference was statistically significant. At 6 months follow up, the results were 90% and 60%, but the difference was not statistically significant. Gross total tumor resection was achieved in 10 cases of the GA group versus 8 in the awake group; however, the difference was not statistically significant. CONCLUSION: Compared to GA, awake craniotomy is a relatively simple non-expensive procedure that allows tumor removal guided by physiology rather than anatomy.

RESUMEN

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are environmentally widespread and persistent chemicals with multiple toxicities reported in experimental animals and humans. These compounds can trigger biological activity by activating the alpha isotype of peroxisome proliferator-activated receptors (PPARs), ligand-activated transcription factors that regulate gene expression; however, some biological effects may occur independently of the receptor. Activation of the peroxisome proliferator-activated receptor alpha (PPARalpha) modulates lipid and glucose homeostasis, cell proliferation and differentiation, and inflammation. Reported immunomodulation in experimental animals exposed to PFOA and PFOS has included altered inflammatory responses, production of cytokines and other proteins, reduced lymphoid organ weights, and altered antibody synthesis. Mounting experimental animal evidence suggests PPARalpha independence of some immune effects. This evidence originates primarily from studies with PPARalpha knockout models exposed to PFOA that demonstrate hepatic peroxisome proliferation, reduced lymphoid organ weights, and altered antibody synthesis. As human PPARalpha expression is significantly less than that of rodents, potential PPARalpha independence indicates that future research must explore mechanisms of action of these compounds, including PPARalpha-dependent and -independent pathways. This multiauthored review contains brief descriptions of current and recently published work exploring immunomodulation by PFOA and PFOS, as well as a short overview of other PPARalpha ligands of therapeutic and environmental interest.

Asunto(s)

Ácidos Alcanesulfónicos/inmunología , Ácidos Alcanesulfónicos/toxicidad , Caprilatos/inmunología , Caprilatos/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Fluorocarburos/inmunología , Fluorocarburos/toxicidad , Factores Inmunológicos/toxicidad , PPAR alfa/metabolismo , Animales , Humanos , Factores Inmunológicos/inmunología , Factores Inmunológicos/metabolismo , PPAR alfa/inmunología , Transactivadores/genética , Transactivadores/metabolismo

RESUMEN

Infection with Mycobacterium tuberculosis (TB) induces pulmonary immunopathology mediated by classical Th1 type of acquired immunity with hepatic involvement in up to 80% of disseminated cases. Since PPAR agonists cause immune responses characterized by a decrease in the secretion of Th1 cytokines, we investigated the impact of activating these receptors on hepatic pathology associated with a well-characterized model of Th1-type pulmonary response. Male Fischer 344 rats were either maintained on a drug-free diet (groups I and II), or a diet containing diethylhexylphthalate (DEHP), a compound transformed in vivo to metabolites known to activate PPARs, for 21 days (groups III and IV). Subsequently, animals were primed with Mycobacterium bovis purified protein derivative (PPD) in a Complete Freund's Adjuvant. Fifteen days later, animals in groups II and IV were challenged with Sepharose 4B beads covalently coupled with PPD, while animals in groups I and III received blank Sepharose beads. Animals with Th1 response (group II) showed a marked structural disruption in the hepatic lobule. Remarkably, these alterations were conspicuously absent in animals which received DEHP (group IV), despite noticeable accumulation of T cells in the periportal triads. Immunostaining and confocal microscopy revealed hepatic accumulation of IFNgamma+ Th1 and IL-4+ Th2 cells in animals from groups II and IV, respectively. Our data suggest a PPARalpha-mediated suppression of the development of a Th1 immune response in the liver, resulting in hepatoprotective effect. However, potentially negative consequences of PPAR activation, such as decreased ability of the immune system to fight infection and interference with the efficacy of vaccines designed to evoke Th1 immune responses, remain to be investigated.

RESUMEN

BACKGROUND: It has been proposed that PPARalpha agonists stimulate Kupffer cells in rodents which in turn, release mitogenic factors leading to hepatic hyperplasia, and eventually cancer. However, Kupffer cells do not express PPARalpha receptors, and PPARalpha agonists stimulate hepatocellular proliferation in both TNFalpha- and TNFalpha receptor-null mice, casting doubt on the involvement of Kupffer cells in the mitogenic response to PPARalpha agonists. This study was therefore designed to investigate whether the PPARalpha agonist PFOA and the Kupffer cell inhibitor methylpalmitate produce opposing effects on hepatocellular proliferation and Kupffer cell activity in vivo, in a manner that would implicate these cells in the mitogenic effects of PPARalpha agonists. METHODS: Male Sprague-Dawley rats were treated intravenously via the tail vein with methylpalmitate 24 hrs prior to perfluorooctanoic acid (PFOA), and were sacrificed 24 hrs later, one hr after an intraperitoneal injection of bromodeoxyuridine (BrdU). Sera were analyzed for TNFalpha and IL-1beta. Liver sections were stained immunohistochemically and quantified for BrdU incorporated into DNA. RESULTS: Data show that PFOA remarkably stimulated hepatocellular proliferation in the absence of significant changes in the serum levels of either TNFalpha or IL-1beta. In addition, methylpalmitate did not alter the levels of these mitogens in PFOA-treated animals, despite the fact that it significantly blocked the hepatocellular proliferative effect of PFOA. Correlation between hepatocellular proliferation and serum levels of TNFalpha or IL-1beta was extremely poor. CONCLUSION: It is unlikely that mechanisms involving Kupffer cells play an eminent role in the hepatic hyperplasia, and consequently hepatocarcinogenicity attributed to PPARalpha agonists. This conclusion is based on the above mentioned published data and the current findings showing animals treated with PFOA alone or in combination with methylpalmitate to have similar levels of serum TNFalpha and IL-1beta, which are reliable indicators of Kupffer cell activity, despite a remarkable difference in hepatocellular proliferation.

RESUMEN

It has been proposed that PPAR-dependent, accelerated catabolism of proinflammatory mediators may contribute to the fast resolution of inflammation. Because retinoid X receptors are obligate heterodimer partners of PPARs, we investigated the impact of deleting hepatocyte-specific RXRalpha on the antiedema effect of PPAR agonists. In wild-type mice (WT), pretreatment with the PPARalpha agonist perfluorooctanoic acid diminished carrageenan-induced paw edema by 66 +/- 10%. This effect was essentially absent (13 +/- 8%) in hepatocyte-specific RXRalpha-deficient mice. Similarly, pretreatment of WT mice with the PPARdelta agonist L-783483 or the PPARgamma agonist L-805645 caused 54 +/- 1% and 38 +/- 8% reduction in carrageenan-induced paw edema, respectively. These effects were also significantly diminished or absent in hepatocyte-specific RXRalpha-deficient mice. In contrast, aspirin reduced carrageenan-induced paw edema equally in WT and hepatocyte-specific RXRalpha-deficient mice. The identification of RXRalpha as an important factor involved in the antiedema effect produced by agonists of the three PPAR subtypes is a significant achievement towards the goal of designing novel, effective anti-inflammatory drugs.

Asunto(s)

Regulación Neoplásica de la Expresión Génica , Prostaglandina-Endoperóxido Sintasas/genética , Envejecimiento/fisiología , Animales , Ciclooxigenasa 2 , Regulación Enzimológica de la Expresión Génica , Masculino , Próstata/crecimiento & desarrollo , Neoplasias de la Próstata , Ratas