RESUMEN
Unintentional weight loss, primarily due to the loss of fat mass rather than muscle mass, is common among patients with Parkinson's disease (PD) and is associated with poor quality of life and accelerated disease progression. Since transgenic mice overexpressing human wild-type α-synuclein (α-Syn mice) are modestly leaner than control mice, and since diabetes, a metabolic disorder, is a major risk factor for PD, we reasoned that high-fat diet-induced diabetes/metabolic dysregulation in α-Syn mice may serve as a robust tool for exploring how early α-synuclein pathology contributes to metabolic dysregulation, leading to weight loss in PD. Thus, α-Syn and age-matched controls were fed a high-fat diet (HFD) chow (60% fat calories) ad libitum for four months. Compared with controls on HFD (control-HFD), α-Syn mice on HFD (α-Syn-HFD) were dramatically leaner. The resistance to gaining weight in α-Syn-HFD mice was accompanied by improved glucose tolerance, a dramatic decrease in fat mass, and an increase in energy expenditure. Despite this leaner phenotype and better glucose tolerance, the mortality was much higher in male α-Syn-HFD mice than in all controls, but was unaffected in females, suggesting protective effects of female sex hormones, as well as lower α-synuclein levels. Immunoblot analysis of insulin signaling in the olfactory bulb, the proposed initial seeding site of α-synuclein pathology, revealed a decrease of IGF-IRß, p GSK, and p mTOR in α-Syn-HFD mice. Since GSK-3ß and mTOR regulate synaptic plasticity, we assessed levels of PSD-95 and synaptophysin in the olfactory bulb. As anticipated, we observed a significant decrease in the levels of PSD-95, along with a potentially compensatory increase in synaptophysin levels. Our results show that α-Syn mice, when challenged with diet-induced diabetes/metabolic dysregulation, clearly reveal a profile of robust metabolic dysfunction, thus providing a sensitive tool for assessing the underlying mechanism of metabolic dysfunction and its impact on weight loss and disease progression in PD. We propose a role for olfactory dysfunction in PD-related unintentional weight loss and suggest that strategies aimed at increasing body weight/BMI will improve the quality of life and prognosis for people living with PD.
RESUMEN
Radiation imaging is extensively applied in nuclear industry for various purposes including fuel characterization. Accurate quantitative evaluation of these radiographic images is difficult by the existing manual process and therefore image analytical methods have been attempted. The method of wavelet transform analysis has been applied on Gamma autoradiography (GAR) images of experimental (U, Pu)O2 mixed oxide (MOX) fuel pins with the objective to investigate the effectiveness of the method for fuel homogeneity characterization. The method was found effective to carry out quantified estimations of size and relative plutonium concentration of the heterogeneous portions in the fuel. The results were validated with theoretically simulated results as practical standards and calibrations are not possible in these samples. The results of wavelet transformation analysis were found to be more accurate with reference to the theoretically simulated values in comparison with conventional pixel analysis applied on the original GAR images.
RESUMEN
Defect engineering is a promising method for improving light harvesting in photocatalytic materials like Zinc sulphide (ZnS). By altering the S/Zn molar ratio during hydrothermal processes, Zn and S defects are successfully introduced into the ZnS crystal. The band structures can be modified by adding defects to the crystal structure of ZnS samples. During the treatment process, defects are formed on the surface. XRD and Raman studies are used for the confirmation of the crystallinity and phase formation of the samples. Using an X-ray peak pattern assessment based on the Debye Scherer model, the Williamson-Hall model, and the size strain plot, it was possible to study the influence of crystal defect on the structural characteristics of ZnS nanoparticles. The band gap (Eg) values were estimated using UV-Vis diffuse spectroscopy (UV-Vis DRS) and found that the Eg is reduced from 3.28 to 3.49 eV by altering the S/Zn molar ratio. Photoluminescence study (PL) shows these ZnS nanoparticles emit violet and blue radiations. In keeping with the results of XRD, TEM demonstrated the nanoscale of the prepared samples and exhibited a small agglomeration of homogenous nanoparticles. Scanning electron microscopy (SEM) was used to examine the surface morphology of the ZnS particles. Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) and X-ray photoelectron spectroscopy (XPS) were used to evaluate and validate the elemental composition. XPS results indicate the presence of defects on the prepared ZnS nanoparticles. For the investigation of vacancy-dependent catalytic activity under exposure to visible light, defective ZnS with different quantities of Zn and S voids are used as catalysts. The lowest S/Zn sample, ZnS0.67 and the highest S/Zn sample, ZnS3, show superior photocatalytic activity.
RESUMEN
Background: Care of COVID-19 patients has been shown to affect the mental health of healthcare personnel (HCP), however, there is little data reflecting psychological health of HCP in India. Aims: The present study was undertaken to assess the prevalence of psychological outcomes and its association with various sociodemographic and occupational factors among the HCP in India. Methodology: A cross-sectional, online survey, using snowball sampling method was conducted between June 1, 2020, and June 22, 2020. The HCP working in COVID-19 designated hospitals across India were invited to participate. Patient Health Questionnaire-4 and 19-item stress-related questionnaire were used to evaluate symptoms of overall anxiety, depression, COVID-19 infection specific anxiety, exhaustion, and workload. Results: In this cross-sectional study with 2334 HCP from 27 states and 7 union territories of India; 17.9% of participants had depression, 18.7% had overall anxiety, 26.5% had exhaustion, 30.3% reported heavy workload, and 25.4% had COVID-19 infection-specific anxiety, respectively. The HCP working in states with higher caseload was a common risk factor for overall anxiety (odds ratio [OR], 1.7; P < 0.001), depression (OR, 1.6; P < 0.001), COVID-19 infection-specific anxiety (OR, 2.5; P < 0.001), exhaustion (OR, 3.1; P < 0.001), and heavy workload (OR, 2.6; P < 0.001). Nurses were more at risk for depression (OR, 2.2; P < 0.001), anxiety specific to COVID-19 infection (OR, 1.3; P = 0.034), and heavy workload (OR, 2.9; P < 0.001); while doctors were more at risk for overall anxiety (OR, 2.0; P = 0.001) and exhaustion (OR, 3.1; P < 0.001). Conclusions: Frontline workers, specifically nurses and doctors, and those working in states with high COVID-19 caseload are more at risk for adverse psychological outcomes. The relatively less prevalence compared with other countries, is perhaps a reflection of measures undertaken, including early lockdown, ensuring better all-round preparedness and social norms.
RESUMEN
Restoration of severely atrophied ridges with conventional implants requires extensive surgical procedures which are totally expensive, and it also involves a great deal of postoperative discomfort to a patient. In such situations, basal implants come to rescue for rehabilitation where it utilizes the cortical bone for anchorage. The availability of several designs of these implants that exist today has made basal implantology flexible enough to accommodate any situation. This article is a case report of the patient whose maxillary arch was fully rehabilitated with endodontically treated teeth and fixed partial denture. The remaining edentulous region in the maxillary left side was treated with corticobasal implants and was rehabilitated with a fixed PFM prosthesis. The above-mentioned case has a follow-up of 3 years, and still, the implant-supported prosthesis provides better function for the patient.
RESUMEN
INTRODUCTION: Endodontically treated teeth have significantly differentphysical properties compared to vital teeth. To ensure functional longevity,endodontically treated teeth must have at least 5 mm of tooth structure coronalto the crestal bone, 2 mm of coronal tooth structure incisal to the preparationfinish line are necessary to ensure functional integrity. AIM AND OBJECTIVES: To evaluate fracture resistance of endodontically treated teeth restored withcustom cast post, custom cast post with variable ferrule height and teethwithout ferrule, prefabricated post with variable ferrule height and teethwithout ferrule. To compare fracture resistance of teeth restored with customcast post and prefabricated post with variable ferrule heights. MATERIALS AND METHODS: Methodology includes selection of teeth, root canal preparation,post space preparation, grouping of samples, Group A-custom cast post andcore with sub groups of variable ferrule height, pattern fabrication, Group A- pattern fabrication for customized cast post. Group B-pattern fabricationfor prefabricated post and core, investing and casting, cementation, custommade acrylic jig preparation, testing of specimens. RESULTS: The differencein the fracture load between the samples of Group A was highly significantat the 0.001 level. Subgroup A4 had highest fracture resistance while GroupA, possessed the least fracture resistance. Subgroups A2, A3 had fractureresistance value intermediate between A1, A4. CONCLUSION: Increasing theferrule height significantly increases (P < 0.001) the fracture resistance ofendodontically treated teeth restored with both custom made cast post andcore and prefabricated post with metal core. Comparatively the custom madecast post and core with variable ferrule height, especially 2 mm ferrule showedsignificant fracture resistance than prefabricated post with metal core. Thepresence of 2 mm ferrule height significantly increases (P < 0.001).
RESUMEN
The aim was to estimate the physiological standardized uptake values (SUVs) on Ga-DOTATATE PET-computed tomography (CT) in normal organs and metastatic tumor lesions (both standard and delayed), and correlating the uptake values and ratios with Krenning Scores (K-score) in patients with metastatic/advanced neuroendocrine tumors (NETs) undergoing PET-CT studies for their management work-up. A total of 32 patients of metastatic NET with 95 discrete tumor lesions were included in this analysis. These patients underwent standard whole-body PET-CT following injection of 2-3 mCi (74-111 MBq) of Ga-DOTATATE at 1-1.5 h. The normal physiological SUVmean of the liver and spleen and SUVmax and SUVmean of tumor lesions were estimated by an in-built automated procedure. These patients also underwent a delayed scan (2.5-3 h) and the same parameters were obtained for the delayed study. The tumorous lesions were further classified on the basis of K-score, and this was correlated with the mean SUVmax on both early and delayed scans. SUVmean ratios (tumor-to-liver and tumor-to-spleen) were also calculated for both time-points and correlated with individual K-scores. In lesions with K-score 4, the mean SUVmax was 32.5 in early and 30.5 in delayed scan, for lesions with K-score of 3 and 2, the mean SUVmax were 17.3, 20, and 9.3, 9.2, respectively, while in K-score 1 (n = 1), the delayed mean SUVmax was found to be more than early mean SUVmax (3.2 to 2.3). Statistical significance was evaluated by paired t test, and the changes in SUVmax was found to be statistically insignificant (P > 0.05) in all 3 K-scores. The paired t test was also performed between early and delayed tumor/liver and tumor/spleen mean SUVmean ratios, and no significant changes were observed across all K scores. The mean SUVmean values of the liver in the standard 1-h scan and delayed scans were 8.05 (range: 3-15) and 8.17 (range: 3.2-16), while for spleen, the values were 18 (range: 8.4-36.7) and 20 (range: 10-38.6), respectively. Statistically significant changes were observed in delayed spleen SUVmean values compared to the early scan (P < 0.05), while for liver SUVmean, the difference was not significant. Thus, in the present study, the SUVmax and SUVmean (range and mean values) for normal liver and spleen, and malignant NET lesions, and tumor-to-liver and tumor-to-spleen SUVmean ratios of different K-scores were generated. As could be theoretically expected in receptor-based PET-CT, there was no significant change in the delayed scan compared to the standard 1-1.5 h values.
Asunto(s)
Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/patología , Compuestos Organometálicos/metabolismo , Tomografía Computarizada por Tomografía de Emisión de Positrones/normas , Adulto , Transporte Biológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/metabolismo , Compuestos Organometálicos/farmacocinética , Estándares de ReferenciaRESUMEN
There is increasing evidence that widespread cortical cerebral blood flow deficits occur early in the course of Parkinson's disease. Although cerebral blood flow measurement has been suggested as a potential biomarker for early diagnosis of Parkinson's disease, as well as a means for tracking response to treatment, the relationship of cerebral blood flow to α-synucleinopathy, a major pathological hallmark of Parkinson's disease, remains unclear. Therefore, we performed arterial spin-labeling magnetic resonance imaging and diffusion tensor imaging on transgenic mice overexpressing human wild-type α-synuclein and age-matched controls to measure cerebral blood flow and degenerative changes. As reported for early-stage Parkinson's disease, α-synuclein mice exhibited a significant reduction in cortical cerebral blood flow, which was accompanied by motor coordination deficits and olfactory dysfunction. Although no overt degenerative changes were apparent in diffusion tensor imaging images, magnetic resonance imaging volumetric analysis revealed a significant reduction in olfactory bulb volume, similar to that seen in Parkinson's disease patients. Our data, representing the first report of cerebral blood flow deficit in an animal model of Parkinson's disease, suggest a causative role for α-synucleinopathy in cerebral blood flow deficits in Parkinson's disease. Thus, α-synuclein transgenic mice comprise a promising model to study Parkinson's disease-related mechanisms of cerebral blood flow deficits and to investigate further its utility as a potential biomarker for Parkinson's disease.
Asunto(s)
Encéfalo/metabolismo , Circulación Cerebrovascular/fisiología , Enfermedad de Parkinson/metabolismo , alfa-Sinucleína/metabolismo , Animales , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Estudios de Casos y Controles , Imagen de Difusión Tensora/métodos , Modelos Animales de Enfermedad , Dopamina/metabolismo , Imagen por Resonancia Magnética/métodos , Masculino , Ratones , Ratones Transgénicos , Trastornos del Olfato/metabolismo , Bulbo Olfatorio/diagnóstico por imagen , Bulbo Olfatorio/fisiopatología , Enfermedad de Parkinson/diagnóstico , Sinucleinopatías/metabolismo , Sinucleinopatías/fisiopatologíaRESUMEN
Although olfactory dysfunction is an early warning sign of Alzheimer's and Parkinson's diseases, and is commonly present in a range of other neurodegenerative disorders, the mechanisms for its pathogenesis are not yet clear. Since fMRI allows the mapping of spatial and temporal patterns of activity in multiple brain regions simultaneously, it serves as a powerful tool to study olfactory dysfunction in animal models of neurodegenerative diseases. Nonetheless, there have been no reports to date of mapping odor-induced activation patterns beyond the olfactory bulb to the extended networks of olfactory and limbic archicortex, likely due to the small size of the mouse brain. Therefore, using an 11.7 T magnet and a blood volume-weighted fMRI technique, we mapped the functional neuroanatomy of the mouse olfactory system. Consistent with reports on imaging of the much larger human brain, we mapped activity in regions of the olfactory bulb, as well as olfactory and limbic archicortex. By using two distinct odorants, we further demonstrated odorant-specific activation patterns. Our work thus provides a methodological framework for fMRI studies of olfactory dysfunction in mouse models of neurodegeneration.
Asunto(s)
Bulbo Olfatorio/fisiología , Vías Olfatorias/fisiología , Animales , Mapeo Encefálico , Estudios de Factibilidad , Imagen por Resonancia Magnética , Masculino , Ratones Endogámicos C57BL , OdorantesRESUMEN
Glial cell line-derived neurotrophic factor (GDNF) is the most potent neuroprotective agent tested in cellular and animal models of Parkinson's disease (PD). However, CNS delivery of GDNF is restricted by the blood-brain barrier (BBB). Using total body irradiation as transplant preconditioning, we previously reported that hematopoietic stem cell (HSC) transplantation (HSCT)-based macrophage-mediated gene therapy could deliver GDNF to the brain to prevent degeneration of nigrostriatal dopamine (DA) neurons in an acute murine neurotoxicity model. Here, we validate this therapeutic approach in a chronic progressive PD model - the MitoPark mouse, with head shielding to avoid inducing neuroinflammation and compromising BBB integrity. Bone marrow HSCs were transduced ex vivo with a lentiviral vector expressing macrophage promoter-driven GDNF and transplanted into MitoPark mice exhibiting well developed PD-like impairments. Transgene-expressing macrophages infiltrated the midbrains of MitoPark mice, but not normal littermates, and delivered GDNF locally. Macrophage GDNF delivery markedly improved both motor and non-motor symptoms, and dramatically mitigated the loss of both DA neurons in the substantia nigra and tyrosine hydroxylase-positive axonal terminals in the striatum. Our data support further development of this HSCT-based macrophage-mediated GDNF delivery approach in order to address the unmet need for a disease-modifying therapy for PD.
Asunto(s)
Neuronas Dopaminérgicas/patología , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Macrófagos/metabolismo , Trastornos Parkinsonianos/patología , Trastornos Parkinsonianos/terapia , Animales , Línea Celular Tumoral , Supervivencia Celular , Expresión Génica , Terapia Genética , Trasplante de Células Madre Hematopoyéticas , Humanos , Ratones , Actividad Motora/genética , Trastornos Parkinsonianos/genética , Trastornos Parkinsonianos/fisiopatologíaRESUMEN
Mitochondrial dysfunction and oxidative stress are very prominent and early features in Parkinson's disease (PD) and in animal models of PD. Thus, antioxidant therapy for PD has been proposed, but in clinical trials such strategies have met with very limited success. Methylene blue (MB), a small-molecule synthetic heterocyclic organic compound that acts as a renewable electron cycler in the mitochondrial electron transport chain, manifesting robust antioxidant and cell energetics-enhancing properties, has recently been shown to have significant beneficial effects in reducing nigrostriatal dopaminergic loss and motor impairment in acute toxin models of PD. However, no studies have investigated the impact of this promising agent in chronic models or for olfactory dysfunction, an early non-motor feature of PD. To test the efficacy of low-dose MB for olfactory dysfunction, motor symptoms, and dopaminergic neurodegeneration, mice were injected with ten subcutaneous doses of 25â¯mg/kg MPTP, plus 250â¯mg/kg intraperitoneal probenecid or saline/probenecid at 3.5-day intervals. Following the onset of olfactory dysfunction, MPTP/probenecid (MPTP/p) and saline/probenecid mice were provided drinking water with or without 1â¯mg/kg/day MB. Oral delivery of low-dose MB significantly ameliorated MPTP/p-induced deficits in motor coordination, as well as degeneration of tyrosine hydroxylase (TH)-positive neurons of the substantia nigra and TH-positive terminals in the striatum. Importantly, olfactory dysfunction was ameliorated by MB treatment, whereas this benefit is not observed with currently available anti-Parkinsonian medications. These results indicate that low-dose MB is a promising neuroprotective intervention for both motor and non-motor features of PD.
Asunto(s)
Encéfalo/efectos de los fármacos , Azul de Metileno/farmacología , Fármacos Neuroprotectores/farmacología , Trastornos Parkinsonianos/patología , Olfato/efectos de los fármacos , Animales , Antioxidantes/farmacología , Conducta Animal/efectos de los fármacos , Encéfalo/patología , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Actividad Motora/efectos de los fármacosRESUMEN
The main objective of this study was to check the validity of using gamma camera as an alternate method to thyroid uptake probe, for counting 25uCi (0.925 MBq) and 50uCi (1.85 MBq) 131I capsules before administration to thyroid patients. Methods: - 10 sets each of 25uCi (0.925 MBq) and 50uCi (1.85 MBq) 131I capsules received from Board Of Radiation and Isotope Technology, Department Of Atomic Energy, India (BRIT, DAE) have been counted individually using thyroid uptake probe for 10 seconds following institutional protocol and also by keeping individual capsule of a set with 8cm gap between each of them .These capsules were also scanned by Scintillation gamma camera for 100 seconds. Capsules having counts within the range of mean ±2 Standard Deviation (SD) were accepted for patient administration. After analysing both the data, correlation coefficient between these two methods has been evaluated. Results: Scanned images were analysed by drawing Identical ROI around each set of 25uCi (0.925 MBq) and 50uCi (1.85 MBq) 131I capsules. Capsules with counts within 2 Standard Deviation from mean were accepted for patient administration. Good correlation coefficient (r >0.95) was observed between these two counts set. Conclusion: Gamma camera based 131I -capsule counting method is an easy and time saving method compared to probe based capsule counting method as we can scan a set of capsules in a single acquisition. It can provide uniformity information for a batch of 131I -capsules and avoid the time consuming method of individual capsule counting with the thyroid uptake probe.
RESUMEN
Parkinson's disease is a chronic neurodegenerative disorder with the core motor features of resting tremor, bradykinesia, rigidity, and postural instability. Non-motor symptoms also occur, and include cognitive dysfunction, mood disorders, anosmia (loss of smell), and REM sleep disturbances. As the development of medications and other therapies for treatment of non-motor symptoms is ongoing, it is essential to have animal models that aid in understanding the neural changes underlying non-motor PD symptoms and serve as a testing ground for potential therapeutics. We investigated several non-motor symptoms in 10 adult male marmosets using the MPTP model, with both the full (n=5) and partial (n=5) MPTP dosing regimens. Baseline data in numerous domains were collected prior to dosing; assessments in these same domains occurred post-dosing for 12 weeks. Marmosets given the partial MPTP dose (designed to mimic the early stages of the disease) differed significantly from marmosets given the full MPTP dose in several ways, including behavior, olfactory discrimination, cognitive performance, and social responses. Importantly, while spontaneous recovery of PD motor symptoms has been previously reported in studies of MPTP monkeys and cats, we did not observe recovery of any non-motor symptoms. This suggests that the neurochemical mechanisms behind the non-motor symptoms of PD, which appear years before the onset of symptoms, are independent of the striatal dopaminergic transmission. We demonstrate the value of assessing a broad range of behavioral change to detect non-motor impairment, anosmia, and differences in socially appropriate responses, in the marmoset MPTP model of early PD.
Asunto(s)
Trastornos Parkinsonianos/psicología , Desempeño Psicomotor/efectos de los fármacos , Sustancia Negra/efectos de los fármacos , Sustancia Negra/patología , Animales , Conducta Animal/efectos de los fármacos , Callithrix , Función Ejecutiva/efectos de los fármacos , Intoxicación por MPTP/patología , Intoxicación por MPTP/psicología , Masculino , Actividad Motora/efectos de los fármacos , Fenotipo , Olfato/efectos de los fármacos , Conducta SocialRESUMEN
The MitoPark mouse, a relatively new genetic model of Parkinson's disease (PD), has a dopaminergic neuron-specific knock-out that inactivates the mitochondrial transcription factor A (Tfam), a protein essential for mitochondrial DNA expression and maintenance. This study used multimodal MRI to characterize the neuroanatomical correlates of PD-related deficits in MitoPark mice, along with functional behavioral tests. Compared with age-matched wild-type animals, MitoPark mice at 30 weeks showed: i) reduced whole-brain volume and increased ventricular volume, indicative of brain atrophy, ii) reduced transverse relaxation time (T2*) of the substantia nigra and striatum, suggestive of abnormal iron accumulation, iii) reduced apparent diffusion coefficient in the substantia nigra, suggestive of neuronal loss, iv) reduced fractional anisotropy in the corpus callosum and substantia nigra, indicative of white-matter damages, v) cerebral blood flow was not significantly affected, and vi) reduced motor activity in open-field tests, reduced memory in novel object recognition tests, as well as decreased mobility in tail suspension tests, an indication of depression. In sum, MitoPark mice recapitulate changes in many MRI parameters reported in PD patients. Multimodal MRI may prove useful for evaluating neuroanatomical correlates of PD pathophysiology in MitoPark mice, and for longitudinally monitoring disease progression and therapeutic interventions for PD.
Asunto(s)
Cuerpo Estriado/patología , Imagen por Resonancia Magnética/métodos , Imagen Multimodal/métodos , Enfermedad de Parkinson/fisiopatología , Sustancia Negra/patología , Testículo/fisiología , Animales , Atrofia/genética , Atrofia/patología , Conducta Animal/fisiología , ADN Mitocondrial/biosíntesis , Proteínas de Unión al ADN/antagonistas & inhibidores , Proteínas de Unión al ADN/genética , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Proteínas del Grupo de Alta Movilidad/antagonistas & inhibidores , Proteínas del Grupo de Alta Movilidad/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Actividad Motora/genéticaRESUMEN
PPARδ (peroxisome proliferator-activated receptor δ) mediates inflammation in response to lipid accumulation. Systemic administration of a PPARδ agonist can ameliorate atherosclerosis. Paradoxically, genetic deletion of PPARδ in hematopoietic cells led to a reduction of atherosclerosis in murine models, suggesting that downregulation of PPARδ expression in these cells may mitigate atherogenesis. To advance this finding forward to potential clinical translation through hematopoietic stem cell transplantation-based gene therapy, we employed a microRNA (miRNA) approach to knock down PPARδ expression in bone marrow cells followed by transplantation of the cells into LDLR-/- mice. We found that knockdown of PPARδ expression in the hematopoietic system caused a dramatic reduction in aortic atherosclerotic lesions. In macrophages, a key component in atherogenesis, knockdown of PPARδ led to decreased expression of multiple pro-inflammatory factors, including monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-1ß and IL-6. Expression of CCR2, a receptor for MCP-1, was also decreased. The downregulation of pro-inflammatory factors is consistent with significant reduction of macrophage presence in the lesions, which may also be attributable to elevation of ABCA1 (ATP-binding cassette, subfamily A, member 1) and depression of adipocyte differentiate-related protein. Furthermore, the abundance of both MCP-1 and matrix metalloproteinase-9 proteins was reduced in plaque areas. Our results demonstrate that miRNA-mediated PPARδ knockdown in hematopoietic cells is able to ameliorate atherosclerosis.
Asunto(s)
Aterosclerosis/genética , Terapia Genética/métodos , PPAR delta/genética , Transportador 1 de Casete de Unión a ATP/genética , Transportador 1 de Casete de Unión a ATP/metabolismo , Animales , Aorta/patología , Aterosclerosis/prevención & control , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Regulación hacia Abajo , Femenino , Regulación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Macrófagos/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Noqueados , MicroARNs/genética , MicroARNs/metabolismo , PPAR delta/metabolismo , Placa Aterosclerótica/genética , Placa Aterosclerótica/patología , Receptores CCR2/genética , Receptores CCR2/metabolismoRESUMEN
INTRODUCTION: Endovascular techniques to retrieve intravascular foreign bodies are a necessary component of the Vascular surgeon's skill set. We report the successful retrieval of an embolized irrigation cannula from the thoracic aorta following aortic valve replacement. PRESENTATION OF CASE: The patient is an 81 year old male who underwent coronary artery bypass grafting and aortic valve replacement. Prior to closure, the aortotomy was irrigated with heparinized saline using a syringe with an olive tip irrigation cannula. When the syringe was handed back to the nursing staff, the tip was noted to be missing but could not be found. Prior to closure of the sternum, the field was searched again for the tip and thus the chest was closed. The missing instrument then prompted an intraoperative chest radiograph that demonstrated a metal irrigation cannula superimposed on the cardiac silhouette. Additionally, a transesophageal echocardiogram was performed, which demonstrated the irrigation cannula within the descending thoracic aorta. Right common femoral artery was accessed and a thoracic aortogram was performed demonstrating the cannula to be lodged in the descending thoracic aorta. Intravascular ultrasound (IVUS) was performed to exclude an aortic abnormality preventing the caudad migration of the cannula. No aortic pathology was identified. A tri-lobed snare was used to grasp the cannula at its tip and withdrawn into the right external iliac artery. The cannula was successfully removed through a transverse arteriotomy in the distal right external iliac artery. The patient's postoperative course was uneventful. CONCLUSION: Endovascular retrieval of intravascular foreign bodies is minimally invasive, relatively simple, and carries minimal morbidity compared to conventional open surgical techniques. This unusual case demonstrates the importance of a working knowledge of techniques and instruments requisite for retrieval of intravascular foreign bodies.
RESUMEN
The objective of this work was to evaluate the necessity of a thyroid phantom in counting a standard capsule during estimation of iodine-131 thyroid uptake using gamma camera methods. For this, camera-based uptake was calculated taking a standard capsule within a thyroid phantom, as well as a standard capsule (without phantom) placed at 5, 10, and 15 cm from the face of the collimator. The values obtained in each setting were compared with the traditional standard thyroid probe-based method. Among these four sets of values, that with the phantom was the closest to the reference probe-based uptake values. Among those without the phantom, the camera-based uptake with the standard at 15 cm from the face of the collimator was closer to the standard probe method. However, as the image at 15 cm would give poor resolution, it would not be feasible to adopt this method for clinical routine. Thus, to conclude, for calculating camera-based uptake, a standard capsule in the phantom gives the best comparable values to the standard probe-based method, indicating the need for the phantom when adopting the gamma camera-based methodology.
Asunto(s)
Cámaras gamma , Radioisótopos de Yodo/metabolismo , Fantasmas de Imagen , Glándula Tiroides/diagnóstico por imagen , Glándula Tiroides/metabolismo , Adulto , Anciano , Transporte Biológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cintigrafía , Adulto JovenRESUMEN
Monte Carlo simulations have been carried out using the FLUKA code to improve the neutron ambient dose equivalent [H*(10)] response of the ZReC (zirconium-lined portable neutron counter responding satisfactorily to neutrons up to 1 GeV) by introducing various neutron absorbers in the system such as cadmium, gadolinium, natural boron, enriched (10)B and borated polythene. It was found that ZReC can be effectively used as a portable neutron monitor by introducing any one of the following perforated layers: 5 mm thick natural boron, 0.5 mm thick enriched (10)B or 1 cm high-density polythene mixed with 50 % boron by weight. The integral response of the instrument was also calculated for some typical reference neutron fields. The relative ambient dose equivalent response of the said system is also found comparable with that of the existing LINUS neutron monitor.
Asunto(s)
Modelos Estadísticos , Neutrones , Radiometría/instrumentación , Radiometría/métodos , Circonio/química , Circonio/efectos de la radiación , Absorción de Radiación , Simulación por Computador , Diseño de Equipo , Análisis de Falla de Equipo , Ensayo de Materiales , Dosis de Radiación , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
UNLABELLED: The objective of the study was to make a quantitative comparison of 24-h thyroid uptake calculated by γ camera-based and thyroid uptake probe-based methods after administration of a diagnostic (131)I capsule in patients with benign thyroid disorders. METHODS: The study group comprised 66 patients, of whom 26 were male (28-67 y old) and 40 female (20-65 y old). These patients had benign thyroid disorders (primarily hyperthyroidism [thyrotoxicosis]), most of whom had been referred for evaluation before radioiodine treatment. (131)I (25 µCi [925 MBq]) was administered, and 24-h thyroid uptake was calculated using a probe-based method and a camera-based method with a medium-energy parallel-hole collimator. The paired t test was used to check the variation in values obtained by these 2 methodologies. RESULT: Of the 66 patients included in this study, 45 had clinical thyrotoxicosis and 21 had nonthyrotoxic multinodular goiter. In the group with thyrotoxicosis, neck uptake ranged from 40.13% to 97.1% by the probe-based method and 36.89% to 95.9% by the camera-based method. In the group with clinically nonthyrotoxic goiter, neck uptake ranged from 1.4% to 38.4% by the probe-based method and 0.6% to 34.8% by the camera-based method. Paired t testing was performed on both groups of patients, and P values were less than 0.05, showing good agreement within the 2 groups of data. CONCLUSION: The camera-based method is a good substitute for the probe-based method; though not producing identical results, the former could be used to derive useful quantitative information on thyroid function.
Asunto(s)
Cámaras gamma , Radioisótopos de Yodo/farmacocinética , Radiofármacos/farmacocinética , Enfermedades de la Tiroides/diagnóstico por imagen , Glándula Tiroides/diagnóstico por imagen , Glándula Tiroides/metabolismo , Adulto , Anciano , Femenino , Bocio Nodular/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Cintigrafía , Tirotoxicosis/diagnóstico por imagenRESUMEN
The FLUKA Monte Carlo simulations are carried out to estimate the (41)Ar concentration inside accelerator vaults of various sizes when proton beams of energy 0.1-1.0 GeV are incident on thick copper and lead targets. Generally (41)Ar concentration is estimated using an empirical formula suggested in the NCRP 144, which assumes the activation is caused only by thermal neutrons alone. It is found that while the analytical and Monte Carlo techniques give similar results for the thermal neutron fluence inside the vault, the (41)Ar concentration is under-predicted by the empirical formula. It is also found that the thermal neutrons contribute â¼41 % to the total (41)Ar production while 56 % production is caused by neutrons between 0.025 and 1 eV. A modified factor is suggested for the use in the empirical expression to estimate the (41)Ar activity 0.1-1.0-GeV proton accelerator enclosures.