ABSTRACT
OBJECTIVES: The prevalence of overweight increases the risk of several non-communicable diseases (NCDs) and, consequently, the costs of health care systems. In this study, we aimed to project the economic burden of NCDs attributable to overweight in Brazil between 2021 and 2030. METHODS: A cohort simulation of adults (17-117 years) using multistate lifetable modeling was used to estimate the costs of NCDs attributable to overweight in Brazil. The projections of direct health care costs (outpatient and inpatient expenses in the Unified Health System) and indirect costs (years of productive life lost) considered different trajectories of the prevalence of overweight between 2021 and 2030. RESULTS: In 2019, the prevalence of overweight was 55.4% in the adult Brazilian population. We estimate that around 1.8 billion international dollars (Int$) would be spent on the direct health care cost of NCDs between 2021 and 2030, through the continued increase in overweight prevalence observed between 2006 and 2020. The indirect costs over the same time would be approximately 20.1 billion Int$. We estimate that halving the annual increase in body mass index slope from the beginning of 2021 until 2030 would save 20.2 million Int$ direct and indirect costs by 2030. In the scenario of keeping the prevalence of overweight observed in 2019 constant until 2030, the savings would be 40.8 million Int$. Finally, in the scenario of a 6.7% reduction in the prevalence of overweight observed in 2019 (to be achieved gradually until 2030), 74.1 million Int$ would be saved. CONCLUSIONS: These results highlight the high economic burden of overweight in the Brazilian adult population.
Subject(s)
Noncommunicable Diseases , Overweight , Adult , Humans , Overweight/epidemiology , Brazil/epidemiology , Financial Stress , Noncommunicable Diseases/epidemiology , Cost of Illness , Health Care CostsABSTRACT
OBJECTIVES: Lack of sufficient physical activity (PA) has been associated with an increased risk of several non-communicable diseases (NCDs) and all-cause mortality. This study aimed to estimate the number of preventable incidence cases of NCDs attributable to insufficient PA in the Chilean population. STUDY DESIGN: Comparative risk assessment modelling study. METHODS: This study examined data from 5834 participants aged ≥20 years from the Chilean National Survey (2016-2017). PA was assessed by the Global Physical Activity Questionnaire (GPAQ), and metabolic equivalent of tasks (METs) were assigned according to PA intensity. Estimated incidence cases of NCDs in Chile in 2019 were obtained from the Global Burden of Disease study. Relative risks for breast cancer, colon cancer, ischaemic heart disease, diabetes and stroke were obtained from a published meta-analysis and applied to the prevalence of insufficient PA estimates through the potential impact fraction equation. RESULTS: High levels of PA (≥8000 MET-min/week) could potentially avoid more than 22,000 (64.6 %) incidence NCD cases, ranging from 498 (10.1 %) preventable cases of breast cancer to 5629 (14.7 %) cases of diabetes. Other modelled scenarios also showed to reduce the incidence cases of all five NCDs but to a lesser extent; where at least PA recommendation was achieved, preventable NCDs were reduced by 6522 cases (18.7 %), and where a 10 % relative reduction in insufficient PA level in the population was achieved, preventable NCDs were reduced by 651 (1.8 %) cases. CONCLUSIONS: The study results provide estimates for the incidence cases of preventable NCDs attributable to insufficient PA, highlighting the important role of PA in NCD prevention in Chile.
Subject(s)
Breast Neoplasms , Diabetes Mellitus , Noncommunicable Diseases , Humans , Female , Noncommunicable Diseases/epidemiology , Noncommunicable Diseases/prevention & control , Chile/epidemiology , Risk Factors , Incidence , Exercise , Diabetes Mellitus/epidemiology , Diabetes Mellitus/prevention & controlABSTRACT
BACKGROUND: The prevalence of overweight/obesity has been increasing globally and in people with Intellectual Disabilities (IDs), this problem is exacerbated even more, which added to a low physical condition that contributes to the deterioration of functionality and increases the risk of developing chronic diseases in the course of life. Therefore, the aim of this study was to establish cut-off points for levels of isometric handgrip and low limb explosive strength in children, adolescents and adults, which identify overweight/obesity in people with IDs and their respective associations. METHODS: The sample was made up of 131 individuals with IDs, belonging to four special and community educational centres in the city of Santiago, Chile. Body mass index (BMI) and waist-to-height ratio (WHR) were used as indicators of overweight/obesity. Handgrip strength was used as a measure of isometric strength, and countermovement jump was used as a measure of low limb explosive strength. For the comparison of variables by age group, the analysis of Ancova, Kruskal-Wallis and chi-square tests were used. The total area under the receiver operating characteristic curve of isometric handgrip and low limb explosive strength was identified as an indicator of overweight/obesity according to age groups. A logistic regression model was used to quantify the effect that strength categories below the cut-off point have on the risk of overweight and obesity. RESULTS: Significant differences were observed between the age groups for body weight, height, BMI and WHR, as well as in the levels of absolute handgrip strength and vertical jump with countermovement (P ≤ 0.05). Children showed the lowest cut-off points for absolute and relative strength. The adolescent group showed the highest cut-off points for relative strength and countermovement jump and adults showed the highest value for absolute strength as indicators of overweight/obesity. Different associations between cut-off points with BMI and WHR were found. CONCLUSIONS: Adolescents showed the highest cut-off point for relative strength and countermovement jump, and adults showed the highest value for absolute strength, according to overweight/obesity indicators (BMI and WHR). It is suggested to adjust resistance training programmes according to age categories for the prevention of overweight/obesity in people with IDs.
ABSTRACT
OBJECTIVES: Parallel to rising obesity prevalence in Brazil, there is expected to be increased direct health care costs related to non-communicable diseases (NCDs). In this study, we estimated the economic burden of NCDs attributable to overweight and obesity in the Brazilian Unified Health System (SUS). METHODS: We used self-reported body mass index of 85,715 adults from the 2019 Brazilian National Health Survey. Annual costs (1 US$ = 2.281 Reais) with inpatient and outpatient procedures were obtained from the Hospital and Ambulatory Information Systems of the Brazilian SUS. Relative risks for cardiovascular disease, chronic respiratory disease, neoplasm, digestive disease, musculoskeletal disorders, diabetes and kidney diseases, sense organ diseases, and neurological disorders were retrieved from the Global Burden of Disease study. RESULTS: Annually, US$ 654 million (95% uncertainty interval: US$ 418.4 to US$ 893.2) direct health care costs related to NCDs were attributable to overweight and obesity. Attributable costs were higher in women than men. Cardiovascular diseases had the highest attributable costs (US$ 289 million), followed by chronic respiratory diseases (US$ 110 million), neoplasms (US$ 96 million), digestive diseases (US$ 60 million), musculoskeletal disorders (US$ 44 million), diabetes and kidney disease (US$ 31 million), sense organ diseases (US$ 22 million) and neurological disorders (US$ 11 million). CONCLUSIONS: Overweight and obesity account for US$ 654 million direct costs of NCDs annually. Effective policies to promote healthy body weight may have economic benefits.
Subject(s)
Cardiovascular Diseases , Diabetes Mellitus , Musculoskeletal Diseases , Nervous System Diseases , Noncommunicable Diseases , Adult , Brazil/epidemiology , Cardiovascular Diseases/epidemiology , Cost of Illness , Diabetes Mellitus/epidemiology , Female , Financial Stress , Health Care Costs , Humans , Male , Obesity/epidemiology , Overweight/epidemiologyABSTRACT
INTRODUCTION: Intraoperative hypotension (IH) is an independent predictor of mortality. Some experts have suggested that ultrasound measurement of the inferior vena cava (IVC) in spontaneous ventilation can predict IH. OBJECTIVE: To evaluate the capacity of ultrasound measures of IVC in spontaneous ventilation to predict episodes of IH after anaesthesia induction. PATIENTS AND METHODS: We studied 55 high-risk cardiac patients undergoing vascular surgery. The maximum (dIVCmax) and minimum (dIVCmin) diameter of the IVC were measured and the collapsibility index CIâ¯=â¯(dIVCmax-dIVCmin)/dIVCmax was calculated prior to anaesthesia induction. Three definitions of IH were used: systolic blood pressure (SBP) less than 100â¯mmHg, mean arterial pressure (MAP) less than 60â¯mmHg, and a decrease in MAP greater than or equal to 30% compared to baseline. RESULTS: There were no significant differences in dIVCmax or in CI between patients presenting IH after anaesthesia induction and those who did not. ROC curves for dIVCmax showed an area under the curve of 0.55 (0.39-0.70), 0.69 (0.48-0.90), and 0.57 (0.42-0.73) and ROC curves for the CI were 0.62 (0.47-0.78), 0.60 (0.41-0.78) and 0.62 (0.47-0.78) for the 3 definitions of IH (<100â¯mmHg, MAPâ¯<â¯60â¯mmHg, and MAP ≥30% baseline), respectively. CONCLUSIONS: Ultrasound measurements of IVC in spontaneous ventilation are not good predictors of IH after anaesthesia induction in these patients. The optimal cut-off points show low specificity and moderate sensitivity for predicting IH.
Subject(s)
Hypotension , Vena Cava, Inferior , Anesthesia, General/adverse effects , Humans , Hypotension/diagnostic imaging , Hypotension/etiology , Ultrasonography , Vascular Surgical Procedures , Vena Cava, Inferior/diagnostic imagingABSTRACT
The transcription factor Hif-1α regulates epithelial to mesenchymal transition and neural crest cell chemotaxis in Xenopus. Hif-1α is only stabilised under low oxygen levels, and the in vivo stabilisation of this factor in neural crest cells is poorly understood. Multiple oxygen-independent Hif-1α regulators have been described in cell cultures and cancer models. Among these, the PDGF pathway has been linked to neural crest development. The present study established a connection between the Pdgf pathway and Hif-1α stabilisation in zebrafish. Specifically, embryos with a disrupted Pdgf pathway were rescued by employing hif-1α mRNA through qPCR and immunohistochemistry techniques. The data suggest that oxygen levels in the neural crest are normal and that Pdgf1aa regulates neural crest migration through Hif-1α expression.
Subject(s)
Cell Movement/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Neural Crest/growth & development , Oxygen/metabolism , Zebrafish Proteins/genetics , Zebrafish/genetics , Animals , Epithelial-Mesenchymal Transition/genetics , Organogenesis/genetics , Xenopus laevis/geneticsABSTRACT
WHAT IS KNOWN AND OBJECTIVE: Use of cisplatin can induce type I hypersensitivity reactions that may also be linked to the quality of the drug utilized. We observed cases of hypersensitivity that appeared to be associated with the brand of cisplatin used. The aim of this study was to compare two different brands of cisplatin in relation to type I hypersensitivity reactions. METHODS: Brand A was used in a tertiary care teaching hospital until 2012, and use of brand B started from January 2013, when the first hypersensitivity cases were observed. Patients were categorized based on symptom. Cisplatin of both brands was analysed by high-performance liquid chromatography (HPLC) and high-resolution electrospray ionization mass spectrometry (ESI-(+)-MS) and characterized according to US Pharmacopeia. RESULTS AND DISCUSSION: There were no cases of hypersensitivity associated with the use of cisplatin brand A, whereas four of 127 outpatients that used cisplatin brand B were affected. The two brands were in accordance with the US Pharmacopeia parameters, and there was no significant difference in the total platinum levels between the two brands when analysed by HPLC. However, high-resolution ESI-(+)-MS analyses show that brand B contains approximately 2.7 times more hydrolysed cisplatin than brand A. WHAT IS NEW AND CONCLUSION: The increase in the hydrolysed form of cisplatin found in brand B may be the cause of the hypersensitivity reaction observed in a subset of patients. We present the first study of the quality of drugs by high-resolution ESI-(+)-MS. Drug regulatory agencies and manufacturers should consider including measurement of hydrolysed cisplatin as a quality criterion for cisplatin formulations.
Subject(s)
Cisplatin/adverse effects , Cisplatin/chemistry , Drug Compounding/methods , Drug Hypersensitivity/etiology , Platinum/chemistry , Antineoplastic Agents/adverse effects , Antineoplastic Agents/chemistry , Chemistry, Pharmaceutical/methods , Chromatography, High Pressure Liquid/methods , Drug Hypersensitivity/prevention & control , Female , Humans , Male , Middle Aged , Spectrometry, Mass, Electrospray Ionization/methodsABSTRACT
We conducted a prospective, descriptive study in the Clinica Anglo Americana, a prívate institution taking care of patients from a medium-high socioeconomic level in Lima. The goal of the study was to determine the frequency of histologic findings in liver biopsies performed by laparoscopy or percutaneously in patients with overweight (body mass index > 25 kg/m2) or obesity (body mass index > 30 kg/m2), and to evaluate the correlation with antropometric variables such as BMI, waist circumference, history of diabetes or hyperlypidemia, and biochemical variables like glycemia, lipid profile, aminotransferases and AST/ALT ratio. Between the years 2001 and 2006 50 patients were biopsied, 29 with overweight and 21 with obesity. Eighteen had simple steatosis and 22 had Non-alcoholic steatohepatitis (NASH) (44%), so 40 patients (80%) had some form of fatty liver. Five patients (10%) had cirrhosis confirmed by biopsy, and in all of them the finding of cirrhosis was completely incidental. Sixty four percent of patients with NASH were obese, like the 5 cirrhotics in our series. Herein we illustrate that in a relatively small sample of patients with obesity and overweight like ours, we found all the forms of the liver steatosis spectrum, from simple steatosis to cirrhosis, with a high frequency of NASH.
Subject(s)
Liver Diseases/complications , Liver Diseases/pathology , Obesity/complications , Adult , Aged , Female , Humans , Liver Diseases/epidemiology , Liver Diseases/metabolism , Male , Middle Aged , Obesity/metabolism , Overweight/complications , Overweight/metabolism , Peru , Prevalence , Prospective Studies , Young AdultABSTRACT
In order to function properly, the brain must be wired correctly during critical periods in early development. Mistakes in this process are hypothesized to occur in disorders like autism and schizophrenia. Later in life, signaling pathways are essential in maintaining proper communication between neuronal and non-neuronal cells, and disrupting this balance may result in disorders like Alzheimer's disease. The Wnt/beta-catenin pathway has a well-established role in cancer. Here, we review recent evidence showing the involvement of Wnt/beta-catenin signaling in neurodevelopment as well as in neurodegenerative diseases. We suggest that the onset/development of such pathological conditions may involve the additive effect of genetic variation within Wnt signaling components and of molecules that modulate the activity of this signaling cascade.
Subject(s)
Gene Expression Regulation , Nervous System Diseases/metabolism , Wnt Proteins/physiology , Alzheimer Disease/metabolism , Animals , Apolipoproteins E/metabolism , Autistic Disorder , Genetic Variation , Humans , Neurodegenerative Diseases/metabolism , Polymorphism, Genetic , Schizophrenia/genetics , Schizophrenia/metabolism , Signal Transduction , Wnt Proteins/metabolismABSTRACT
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, which is probably caused by the cytotoxic effect of the amyloid beta-peptide (Abeta). We report here molecular changes induced by Abeta, both in neuronal cells in culture and in rats injected in the dorsal hippocampus with preformed Abeta fibrils, as an in vivo model of the disease. Results indicate that in both systems, Abeta neurotoxicity resulted in the destabilization of endogenous levels of beta-catenin, a key transducer of the Wnt signaling pathway. Lithium chloride, which mimics Wnt signaling by inhibiting glycogen synthase kinase-3beta promoted the survival of post-mitotic neurons against Abeta neurotoxicity and recovered cytosolic beta-catenin to control levels. Moreover, the neurotoxic effect of Abeta fibrils was also modulated with protein kinase C agonists/inhibitors and reversed with conditioned medium containing the Wnt-3a ligand. We also examined the spatial memory performance of rats injected with preformed Abeta fibrils in the Morris water maze paradigm, and found that chronic lithium treatment protected neurodegeneration by rescuing beta-catenin levels and improved the deficit in spatial learning induced by Abeta. Our results are consistent with the idea that Abeta-dependent neurotoxicity induces a loss of function of Wnt signaling components and indicate that lithium or compounds that mimic this signaling cascade may be putative candidates for therapeutic intervention in Alzheimer's patients.
Subject(s)
Alzheimer Disease/metabolism , Nerve Degeneration/metabolism , Proteins/metabolism , Signal Transduction/physiology , Alzheimer Disease/drug therapy , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Animals , Behavior, Animal/drug effects , Cell Death/drug effects , Cell Death/physiology , Cells, Cultured , Culture Media, Conditioned/pharmacology , Cytoskeletal Proteins/metabolism , Humans , Isoenzymes/metabolism , Kidney/cytology , Lithium/pharmacology , Memory Disorders/metabolism , Memory Disorders/pathology , Mice , Nerve Degeneration/drug therapy , Nerve Degeneration/pathology , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Protein Kinase C/metabolism , Proteins/genetics , Rats , Rats, Sprague-Dawley , Trans-Activators/metabolism , Transfection , Wnt Proteins , Wnt3 Protein , Wnt3A Protein , beta CateninABSTRACT
Acetylcholinesterase (AChE) has been found to be associated with the core of senile plaques. We have shown that AChE interacts with the amyloid beta-peptide (Abeta) and promotes amyloid fibril formation by a hydrophobic environment close to the peripheral anionic binding site (PAS) of the enzyme. Here we present evidence for the structural motif of AChE involved in this interaction. First, we modeled the docking of Abeta onto the structure of Torpedo californica AChE, and identified four potential sites for AChE-Abeta complex formation. One of these, Site I, spans a major hydrophobic sequence exposed on the surface of AChE, which had been previously shown to interact with liposomes [Shin et al. (1996) Protein Sci. 5, 42-51]. Second, we examined several AChE-derived peptides and found that a synthetic 35-residue peptide corresponding to the above hydrophobic sequence was able to promote amyloid formation. We also studied the ability to promote amyloid formation of two synthetic 24-residue peptides derived from the sequence of a Omega-loop, which has been suggested as an AChE-Abeta interacting motif. Kinetic analyses indicate that only the 35-residue hydrophobic peptide mimics the effect of intact AChE on amyloid formation. Moreover, RP-HPLC analysis revealed that the 35-residue peptide was incorporated into the growing Abeta-fibrils. Finally, fluorescence binding studies showed that this peptide binds Abeta with a K(d) = 184 microM, independent of salt concentration, indicating that the interaction is primarily hydrophobic. Our results indicate that the homologous human AChE motif is capable of accelerating Abeta fibrillogenesis.
Subject(s)
Acetylcholinesterase/chemistry , Amyloid beta-Peptides/chemistry , Plaque, Amyloid/chemistry , Acetylcholinesterase/isolation & purification , Amino Acid Sequence , Animals , Brain Chemistry , Cattle , Humans , Models, Molecular , Molecular Sequence Data , Plaque, Amyloid/ultrastructure , Protein Conformation , Solubility , TorpedoABSTRACT
Proximate composition, fatty acid profile, essential aminoacid and minerals were determined in twelve fish species (armadillo, bocachico, cachama, carpeta, corvina, lisa, mero, merluza, pargo, robalo, tilapia and trucha). Proximate analysis: moisture, protein and ash, were performed using AOAC methodology, fat by Bligh and Dyer method, fatty acids by Gas Chromatography, aminoacid using High Performance Liquid Chromatography and minerals by spectrophotometric method. Results showed that moisture varies between 70.49% for Armadillo and 78.64% for Mero, protein between 18.70% for Merluza and 25.53 for Armadillo, ash between 0.94% for Mero and 2.13% for Carpeta and fat between 1.12% for Pargo and 6.15% for Cachama. Unsaturated fatty acids (omega 3) were the most common found for all the spices. Essential amino acids studied were present in all the spices. Tilapia (10.938 g/100 g of fish), Bocachico (9.231 g/100 g of fish) and Mero (8.738 g/100 g of fish) shown greater content of essential amino acids. Phosphorous was the most concentrated mineral with a mean value of 238.13 mg/100 g of fish followed by calcium with 42.11 mg/100 g of fish. It was concluded that all studied species are an excellent source of protein, omega 3 fatty acids and minerals.
Subject(s)
Commerce , Fatty Acids/analysis , Fishes , Minerals/analysis , Amino Acids, Essential/analysis , Animals , Nutritive Value , VenezuelaABSTRACT
Alzheimer's disease (AD) is a neurodegenerative disease with progressive dementia accompanied by three main structural changes in the brain: diffuse loss of neurons; intracellular protein deposits termed neurofibrillary tangles (NFT) and extracellular protein deposits termed amyloid or senile plaques, surrounded by dystrophic neurites. Two major hypotheses have been proposed in order to explain the molecular hallmarks of the disease: The 'amyloid cascade' hypothesis and the 'neuronal cytoskeletal degeneration' hypothesis. While the former is supported by genetic studies of the early-onset familial forms of AD (FAD), the latter revolves around the observation in vivo that cytoskeletal changes - including the abnormal phosphorylation state of the microtubule associated protein tau - may precede the deposition of senile plaques. Recent studies have suggested that the trafficking process of membrane associated proteins is modulated by the FAD-linked presenilin (PS) proteins, and that amyloid beta-peptide deposition may be initiated intracellularly, through the secretory pathway. Current hypotheses concerning presenilin function are based upon its cellular localization and its putative interaction as macromolecular complexes with the cell-adhesion/signaling beta-catenin molecule and the glycogen synthase kinase 3beta (GSK-3beta) enzyme. Developmental studies have shown that PS proteins function as components in the Notch signal transduction cascade and that beta-catenin and GSK-3beta are transducers of the Wnt signaling pathway. Both pathways are thought to have an important role in brain development, and they have been connected through Dishevelled (Dvl) protein, a known transducer of the Wnt pathway. In addition to a review of the current state of research on the subject, we present a cell signaling model in which a sustained loss of function of Wnt signaling components would trigger a series of misrecognition events, determining the onset and development of AD.
Subject(s)
Alzheimer Disease/metabolism , Alzheimer Disease/physiopathology , Proto-Oncogene Proteins/metabolism , Signal Transduction/physiology , Zebrafish Proteins , Alzheimer Disease/pathology , Animals , Humans , Wnt ProteinsABSTRACT
OBJECTIVE: To alert pediatricians about the possibillity of childhood Idiopathic Pulmonary Hemosiderosis, in cases of anemia associated with chronic lung disease. METHODS: This article documents a case of Idiopathic Pulmonary Hemosiderosis in a 6 year-old child, with histopathological documentation, and reviews it against published literature. RESULTS: A 6 year-old child with history of anemia and lung disease characterized by wheezing, recurrent pneumonia and digital clubbing was admitted to the hospital for investigation, where he suffered sudden respiratory failure and hemoptysis.He was submitted to a lung biopsy which showed a histopathological diagnosis compatible with pulmonary hemosiderosis. Therapy with high doses of corticosteroids was initiated with a good early response. After two and a half months of therapy he had a new bleeding episode, culminating in death. CONCLUSIONS: Idiopathic Pulmonary Hemosiderosis should be included as a possible diagnosis of children with anemia and chronic lung disease. This case is a good example.
ABSTRACT
Occlusion of the left anterior descending coronary artery during angioplasty has a high mortality rate despite emergent myocardial revascularization. We describe two cases of coronary artery bypass grafting on beating heart without extracorporeal circulation to perform emergency operations after failed angioplasty.
Subject(s)
Angioplasty, Balloon, Coronary , Coronary Artery Bypass , Aged , Coronary Angiography , Coronary Disease/diagnosis , Coronary Disease/therapy , Emergencies , Follow-Up Studies , Humans , Male , Stents , Treatment FailureABSTRACT
Acetylcholinesterase (AChE), the enzyme involved in the hydrolysis of the neurotransmitter acetylcholine, has been implicated in non-cholinergic actions which may play a role in neurodegenerative diseases such as Alzheimer's disease. To study the potential cytotoxicity of brain AChE, the effects of affinity purified AChE were analyzed on neuronal (Neuro 2a) and glial-like (B12) cells. LDH release and MTT reduction assays showed that AChE was toxic; the toxicity was dependent on the enzyme concentration, time of incubation and cellular density. The toxic effect of AChE was not related to its catalytic activity, since the anti-cholinesterase drug BW284C51 and heat inactivation were unable to block the effects of the enzyme. When cells were incubated at 4 degrees C, toxicity was completely blocked, in contrast to cells incubated at 37 degrees C. The presence of serum in the culture medium inhibited the toxic effects of AChE. Cytoplasmic shrinkage, condensation and fragmentation of nucleus as well as DNA strand breaks detected with the TUNEL technique indicated that apoptotic cell death is involved in the effect of AChE. Considering that we have previously shown that AChE promotes the assembly of beta-amyloid peptide into neurotoxic amyloid fibrils, it is conceivable that the neurotoxicity of AChE shown here may play a role in the neuronal degeneration observed in Alzheimer's disease.
Subject(s)
Acetylcholinesterase/toxicity , Neuroglia/drug effects , Neurons/drug effects , Acetylcholinesterase/metabolism , Alzheimer Disease/metabolism , Animals , Biotin , Blood Proteins/pharmacology , Cattle , Cell Count , Cold Temperature , DNA Fragmentation , Deoxyuracil Nucleotides , Enzyme Activation/physiology , Mice , Neuroblastoma , Neurofibrillary Tangles/enzymology , Neuroglia/cytology , Neurons/cytology , Staining and Labeling , Tumor Cells, Cultured/cytology , Tumor Cells, Cultured/drug effectsABSTRACT
Alzheimer's disease (AD) is associated with a reduction in cholinergic activity as a result of specific neuronal loss. Current potential treatments for the disease include both cholinomimetic drugs and anticholinesterase inhibitors. One of the drugs approved by the FDA is tacrine (9-amine-1,2,3,4 tetrahydroacridine; THA), a strong acetylcholinesterase (AChE) inhibitor. We have studied the effects of tacrine on glial and neuronal cells in culture assessing cell survival and viability and morphology. Lactate dehydrogenase (LDH) activity and methylthiazol-diphenyl-tetrazolium (MTT) reduction were used as toxicity indicators. We found that tacrine toxicity on rat B12 glial cells and mouse Neuro 2A cells was strongly dependent on its concentration (up to 500 microM) and time of exposure. The toxic effect was not prevented by serum factors nor by bovine serum albumin. Fluorescein-conjugated phalloidin was used to examine the arrangement of actin filaments at substrate adhesion regions and cell-cell contacts. Primary events following exposure to tacrine included changes in cell morphology, disappearance of actin filament bundles, and disruption of focal adhesion contacts. At concentrations between 10 and 50 microM, tacrine induced neurite outgrowth in Neuro 2A cells, an effect that was not observed in B12 cells, suggesting that certain tacrine effects could be specific for neuronal cells. Although similar trends of response were observed for both cell types, some differences between undifferentiated and differentiated cells were apparent.
Subject(s)
Neurons/drug effects , Tacrine/toxicity , Animals , Cell Differentiation/drug effects , Cell Size/drug effects , Dose-Response Relationship, Drug , Glioma , Mice , Neuroblastoma , Neuroglia/drug effects , Neurons/pathology , Rats , Tumor Cells, CulturedABSTRACT
Se evaluaron 98 tumores renales para analizar, sobre la base de la forma de presentación y diagnóstico, las características y su evolución. Fueron separados en tres grupos: sintomáticos, pseudoincidentales e incidentales. Se pudo determinar que cuando un tumor renal se manifiesta clínicamente, la hematuria es el signo más frecuente, que el 41 por ciento de los tumores fueron de hallazgo pseudoincidental e incidental, que la ecografía presentó alto grado de sensibilidad y especificidad en el hallazgo de tumores asintomáticos y que los tumores de hallazgo incidental tienen una evoluciónh más benmigna que cuando son sintomáticos, permitiendo en ciertos casos seleccionados mantener una conducta expectante o bien tratamiento conservador
Subject(s)
Humans , Kidney Neoplasms/classification , Kidney Neoplasms/diagnosis , Hematuria/diagnosis , UltrasonographyABSTRACT
Se evaluaron 98 tumores renales para analizar, sobre la base de la forma de presentación y diagnóstico, las características y su evolución. Fueron separados en tres grupos: sintomáticos, pseudoincidentales e incidentales. Se pudo determinar que cuando un tumor renal se manifiesta clínicamente, la hematuria es el signo más frecuente, que el 41 por ciento de los tumores fueron de hallazgo pseudoincidental e incidental, que la ecografía presentó alto grado de sensibilidad y especificidad en el hallazgo de tumores asintomáticos y que los tumores de hallazgo incidental tienen una evoluciónh más benmigna que cuando son sintomáticos, permitiendo en ciertos casos seleccionados mantener una conducta expectante o bien tratamiento conservador(AU)
Subject(s)
Humans , Kidney Neoplasms/classification , Kidney Neoplasms/diagnosis , Ultrasonography , Hematuria/diagnosisABSTRACT
A 20-year experience with the treatment of 74 patients (83.8% children) for foreign body aspiration is reviewed. The object of this review is to show the clinical manifestations, the radiological findings, the nature and distribution in the bronchial tree, and complications due to longstanding (months or years) foreign bodies in the bronchial tree. The most common foreign bodies found were peanuts (13.5%), corn (13.5%), and beans (13.5%). The most frequent clinical manifestation was choking (67.5%), and the most frequent radiological finding was atelectasis (41.8%). The most serious complication was bronchiectasis needing resection in six patients who had the foreign body retained for years in the bronchial tree. In conclusion, in spite of an obvious foreign body in the tracheobronchial tree many cases are not diagnosed, and a longstanding foreign body in the airway may be responsible for irreversible complications.