RESUMO
Neuronal loss is the ultimate pathophysiologic event in central nervous system (CNS) diseases and replacing these neurons is one of the most significant challenges in regenerative medicine. Providing a suitable microenvironment for new neuron engraftment, proliferation, and synapse formation is a primary goal for 3D bioprinting. Among the various biomaterials, gelatin methacrylate (GelMA) stands out due to its Arg-Gly-Asp (RGD) domains, which assure its biocompatibility and degradation under physiological conditions. This work aimed to produce different GelMA-based bioink compositions, verify their mechanical and biological properties, and evaluate their ability to support neurogenesis. We evaluated four different GelMA-based bioink compositions; however, when it came to their biological properties, incorporating extracellular matrix components, such as GeltrexTM, was essential to ensure human neuroprogenitor cell viability. Finally, GeltrexTM: 8% GelMA (1:1) bioink efficiently maintained human neuroprogenitor cell stemness and supported neuronal differentiation. Interestingly, this bioink composition provides a suitable environment for murine astrocytes to de-differentiate into neural stem cells and give rise to MAP2-positive cells.
RESUMO
Given the ever-increasing prevalence of type 2 diabetes and obesity, the pressure on global healthcare is expected to be colossal, especially in terms of blindness. Electroretinogram (ERG) has long been perceived as a first-use technique for diagnosing eye diseases, and some studies suggested its use for preventable risk factors of type 2 diabetes and thereby diabetic retinopathy (DR). Here, we show that in a non-evoked mode, ERG signals contain spontaneous oscillations that predict disease cases in rodent models of obesity and in people with overweight, obesity, and metabolic syndrome but not yet diabetes, using one single random forest-based model. Classification performance was both internally and externally validated, and correlation analysis showed that the spontaneous oscillations of the non-evoked ERG are altered before oscillatory potentials, which are the current gold-standard for early DR. Principal component and discriminant analysis suggested that the slow frequency (0.4-0.7 Hz) components are the main discriminators for our predictive model. In addition, we established that the optimal conditions to record these informative signals, are 5-minute duration recordings under daylight conditions, using any ERG sensors, including ones working with portative, non-mydriatic devices. Our study provides an early warning system with promising applications for prevention, monitoring and even the development of new therapies against type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Eletrorretinografia/métodos , Fatores de Risco , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/prevenção & controle , ObesidadeRESUMO
INTRODUCTION: Bipolar disorder (BD) is a mood disorder characterized by the occurrence of depressive episodes alternating with episodes of elevated mood (known as mania). There is also an increased risk of other medical comorbidities. OBJECTIVES: This work uses a systems biology approach to compare BD treated patients with healthy controls (HCs), integrating proteomics and metabolomics data using partial correlation analysis in order to observe the interactions between altered proteins and metabolites, as well as proposing a potential metabolic signature panel for the disease. METHODS: Data integration between proteomics and metabolomics was performed using GC-MS data and label-free proteomics from the same individuals (N = 13; 5 BD, 8 HC) using generalized canonical correlation analysis and partial correlation analysis, and then building a correlation network between metabolites and proteins. Ridge-logistic regression models were developed to stratify between BD and HC groups using an extended metabolomics dataset (N = 28; 14 BD, 14 HC), applying a recursive feature elimination for the optimal selection of the metabolites. RESULTS: Network analysis demonstrated links between proteins and metabolites, pointing to possible alterations in hemostasis of BD patients. Ridge-logistic regression model indicated a molecular signature comprising 9 metabolites, with an area under the receiver operating characteristic curve (AUROC) of 0.833 (95% CI 0.817-0.914). CONCLUSION: From our results, we conclude that several metabolic processes are related to BD, which can be considered as a multi-system disorder. We also demonstrate the feasibility of partial correlation analysis for integration of proteomics and metabolomics data in a case-control study setting.
Assuntos
Transtorno Bipolar , Metabolômica , Estudos de Casos e Controles , Hemostasia , Humanos , Metabolômica/métodos , ProteômicaRESUMO
The effects of neuroinvasion by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) become clinically relevant due to the numerous neurological symptoms observed in Corona Virus Disease 2019 (COVID-19) patients during infection and post-COVID syndrome or long COVID. This study reports the biofabrication of a 3D bioprinted neural-like tissue as a proof-of-concept platform for a more representative study of SARS-CoV-2 brain infection. Bioink is optimized regarding its biophysical properties and is mixed with murine neural cells to construct a 3D model of COVID-19 infection. Aiming to increase the specificity to murine cells, SARS-CoV-2 is mouse-adapted (MA-SARS-CoV-2) in vitro, in a protocol first reported here. MA-SARS-CoV-2 reveals mutations located at the Orf1a and Orf3a domains and is evolutionarily closer to the original Wuhan SARS-CoV-2 strain than SARS-CoV-2 used for adaptation. Remarkably, MA-SARS-CoV-2 shows high specificity to murine cells, which present distinct responses when cultured in 2D and 3D systems, regarding cell morphology, neuroinflammation, and virus titration. MA-SARS-CoV-2 represents a valuable tool in studies using animal models, and the 3D neural-like tissue serves as a powerful in vitro platform for modeling brain infection, contributing to the development of antivirals and new treatments for COVID-19.
Assuntos
COVID-19 , SARS-CoV-2 , Animais , Encéfalo , COVID-19/complicações , Humanos , Camundongos , Neurônios , Síndrome de COVID-19 Pós-AgudaRESUMO
Omics sciences have been facing challenges in different fields, especially in life sciences. One of these challenges involves assessing biology into systems interpretation. With the advance of genomics, molecular biology has been projected into the realm of systems biology. In a different direction, systems approaches are making definitive strides toward scientific understanding and biotechnological applications. Separation techniques provided meaningful progress in the omics era, conducting the classical molecular biology to contemporary systems biology. In this introductory chapter, the relevance of these techniques to the development of different omics sciences, within the systems biology context, will be discussed.
Assuntos
Genômica , Biologia de Sistemas , Biologia MolecularRESUMO
For cardiovascular disease prevention, statins alone or combined with ezetimibe have been recommended to achieve low-density lipoprotein cholesterol targets, but their effects on other lipids are less reported. This study was designed to examine lipid changes in subjects with ST-segment elevation myocardial infarction (STEMI) after two highly effective lipid-lowering therapies. Twenty patients with STEMI were randomized to be treated with rosuvastatin 20 mg QD or simvastatin 40 mg combined with ezetimibe 10 mg QD for 30 days. Fasting blood samples were collected on the first day (D1) and after 30 days (D30). Lipidomic analysis was performed using the Lipidyzer platform. Similar classic lipid profile was obtained in both groups of lipid-lowering therapies. However, differences with the lipidomic analysis were observed between D30 and D1 for most of the analyzed classes. Differences were noted with lipid-lowering therapies for lipids such as FA, LPC, PC, PE, CE, Cer, and SM, notably in patients treated with rosuvastatin. Correlation studies between classic lipid profiles and lipidomic results showed different information. These findings seem relevant, due to the involvement of these lipid classes in crucial mechanisms of atherosclerosis, and may account for residual cardiovascular risk.Randomized clinical trial: ClinicalTrials.gov, NCT02428374, registered on 28/09/2014.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/sangue , Quimioterapia Combinada/métodos , Ezetimiba/uso terapêutico , Feminino , Humanos , Hipercolesterolemia/tratamento farmacológico , Lipídeos/fisiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Rosuvastatina Cálcica/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/metabolismo , Sinvastatina/uso terapêuticoRESUMO
Resumen Objetivo: Identificar la mejor intervención costo-efectividad para el tratamiento de obesidad grado I y II, en el primer nivel de atención para población sin seguridad social, que requiera los servicios del Instituto de Salud y Bienestar (INSABI) Material y Métodos: Se realizó un análisis de costo-efectividad desde la perspectiva del proveedor. Se diseñaron y calcularon los costos de tres tratamientos para la obesidad I y II en usuarios del primer nivel de atención a la salud que carecen de seguridad social, en el municipio de Coatetelco, Morelos. Cada tratamiento fue estimado para el periodo de un año. Los indicadores de efectividad fueron obtenidos a través de estudios previos con características similares a las intervenciones diseñadas. Resultados: La intervención que presento un mayor costo, fue el tratamiento farmacológico con $88,899.26 USD, seguida del tratamiento nutricional con un costo de $31,647.57 USD y $57,189.49 USD en el tratamiento integral. El coeficiente de efectividad obtenido fue de 0.1906 para el tratamiento nutricional, seguido del tratamiento farmacológico con 0.2168 y 0.2531 en el tratamiento integral. Conclusiones: El tratamiento nutricional es la mejor intervención costo- efectividad en pacientes con obesidad grado I y II que carecen de seguridad social y que reciben seguimiento en el primer nivel de atención a la salud. La inversión en estos tratamientos puede contribuir a disminuir los factores de riesgo para el desarrollo de enfermedades crónicas en México.
Abstract Objective: To identify the most cost-effective intervention for the treatment of grade I and II obesity in the first level of care for a population without social security that requires the services of the Institute of Health and Wellbeing (INSABI). Material and Methods: A cost-effectiveness analysis was carried out from the provider's perspective. The costs of three treatments for obesity I and II in users of the first level of health care who lack social security were designed and calculated in the municipality of Coatetelco, Morelos. Each treatment was estimated for a period of one year. The effectiveness indicators were obtained through previous studies with characteristics similar to the designed interventions. Results: The intervention that presented the highest cost was drug treatment with $ 88,899.26 USD, followed by nutritional treatment with a cost of $ 31,647.57 USD and $ 57,189.49 USD in comprehensive treatment. The coefficient of effectiveness obtained was 0.1906 for nutritional treatment, followed by pharmacological treatment with 0.2168 and 0.2531 in comprehensive treatment. Conclusions: Nutritional treatment is the most cost-effective intervention in patients with grade I and II obesity who lack social security is nutritional treatment and who receive care at the first level of health care. Investing in these treatments can help reduce risk factors for the development of chronic diseases in Mexico.
RESUMO
A better understanding of the proteome profile after bipolar disorder (BD) and schizophrenia (SCZ) treatment, besides monitoring disease progression, may assist on the development of novel therapeutic strategies with the ability to reduce or control possible side effects. In this pilot study, proteomics analysis employing nano liquid chromatography coupled to mass spectrometry (nLC-MS) and bioinformatic tools were applied to identify differentially abundant proteins in serum of treated BD and SCZ patients. In total, 10 BD patients, 10 SCZ patients, and 14 healthy controls (HC) were included in this study. 24 serum proteins were significantly altered (p < 0.05) in BD and SCZ treated patients and, considering log2FC > 0.58, 8 proteins presented lower abundance in the BD group, while 7 proteins presented higher abundance and 2 lower abundance in SCZ group when compared against HC. Bioinformatics analysis based on these 24 proteins indicated two main altered pathways previously described in the literature; furthermore, it revealed that opposite abundances of the complement and coagulation cascades were the most significant biological processes involved in these pathologies. Moreover, we describe disease-related proteins and pathways associations suggesting the necessity of clinical follow-up improvement besides treatment, as a precaution or safety measure, along with the disease progression. Further biological validation and investigations are required to define whether there is a correlation between complement and coagulation cascade expression for BD and SCZ and cardiovascular diseases.
Assuntos
Transtorno Bipolar/patologia , Fatores de Coagulação Sanguínea/análise , Proteínas do Sistema Complemento/análise , Esquizofrenia/patologia , Adulto , Biomarcadores Farmacológicos , Transtorno Bipolar/sangue , Transtorno Bipolar/imunologia , Fatores de Coagulação Sanguínea/metabolismo , Proteínas Sanguíneas/análise , Cromatografia Líquida/métodos , Proteínas do Sistema Complemento/metabolismo , Biologia Computacional/métodos , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , Espectrometria de Massas/métodos , Projetos Piloto , Proteômica/métodos , Esquizofrenia/sangue , Esquizofrenia/imunologiaRESUMO
The pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is receiving worldwide attention, due to the severity of the disease (COVID-19) that resulted in more than a million global deaths so far. The urgent need for vaccines and antiviral drugs is mobilizing the scientific community to develop strategies for studying the mechanisms of SARS-CoV-2 infection, replication kinetics, pathogenesis, host-virus interaction, and infection inhibition. In this work, we review the strategies of tissue engineering in the fabrication of three-dimensional (3D) models used in virology studies, which presented many advantages over conventional cell cultures, such as complex cytoarchitecture and a more physiological microenvironment. Scaffold-free (spheroids and organoids) and scaffold-based (3D scaffolding and 3D bioprinting) approach allow the biofabrication of more realistic models relevant to the pandemic, to be used as in vitro platforms for the development of new vaccines and therapies against COVID-19.
Assuntos
Bioimpressão , SARS-CoV-2/patogenicidade , Esferoides Celulares , Engenharia Tecidual/métodos , Enzima de Conversão de Angiotensina 2/fisiologia , Animais , Antivirais/farmacologia , Humanos , Organoides , SARS-CoV-2/efeitos dos fármacos , Alicerces TeciduaisRESUMO
BACKGROUND: Imbalances in metal concentrations have been suggested to contribute to the pathophysiology of different brain disorders, such as bipolar disorder (BD) and schizophrenia (SCZ). OBJECTIVES: The aim of this exploratory study is to evaluate the association between the concentrations of macro/trace elements in serum from BD and SCZ patients considering the effects from different treatments. METHODS: Eleven subjects with SCZ, seven with BD treated with lithium (BDL) and eight subjects with BD treated with other medications except lithium (BDN) were recruited for the study, as well as eleven healthy controls (HC). Serum concentrations of eleven macro/trace elements (Se, Zn, Fe, K, Ca, Mg, P, Al, Cu, Mn, and Ni) were determined using inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Se and Zn concentrations were significantly lower for patients with SCZ and BD in comparison to HC by one-way ANOVA test. Moreover, serum concentrations for Fe were significantly higher (p < 0.05) in BDN (548 ± 92 µg L-1) and SCZ (632 ± 279 µg L-1) in comparison to HC (421 ± 121 µg L-1). A significant negative correlation was reported between Se and Fe in BDL group (r = -0.935, p < 0.05). In addition, a significantly higher Cu/Zn ratio was determined in SCZ group against HC (ratio = 2.4, p = 0.028). CONCLUSIONS: The obtained results suggest that the imbalance in Fe concentrations is an effect of BD treatment. Lithium is supposed to have an antagonist effect for Se in BDL patients. A negative correlation reported between Fe and BMI in SCZ group could be related to antipsychotic treatment and the Cu/Zn ratio reported could be considered as a suggesting parameter to relate oxidative stress to SCZ. Future studies including larger number of patients with SCZ and BD before and after treatment are necessary to confirm the investigative results presented herein.
Assuntos
Transtorno Bipolar/tratamento farmacológico , Lítio/farmacologia , Esquizofrenia/tratamento farmacológico , Oligoelementos/farmacologia , Adulto , Biomarcadores/sangue , Transtorno Bipolar/sangue , Transtorno Bipolar/diagnóstico , Estudos de Coortes , Feminino , Humanos , Lítio/administração & dosagem , Lítio/sangue , Masculino , Espectrometria de Massas , Metabolômica , Estresse Oxidativo/efeitos dos fármacos , Proteômica , Esquizofrenia/sangue , Esquizofrenia/diagnóstico , Oligoelementos/administração & dosagem , Oligoelementos/sangueRESUMO
Selenium and selenoproteins are important components of living organisms that play a role in different biological processes. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is a powerful analytical technique that has been employed to obtain distribution maps of selenium in biological tissues in a direct manner, as well as in selenoproteins, previously separated by their molecular masses and isoelectric points using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). In this chapter, we present the protocols to perform LA-ICP-MS imaging experiments, allowing the distribution visualization and determination of selenium and/or selenoproteins in biological systems.
Assuntos
Eletroforese em Gel Bidimensional , Imagem Molecular/métodos , Selênio , Selenoproteínas/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Eletroforese em Gel Bidimensional/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodosRESUMO
Amongst all omics sciences, there is no doubt that metabolomics is undergoing the most important growth in the last decade. The advances in analytical techniques and data analysis tools are the main factors that make possible the development and establishment of metabolomics as a significant research field in systems biology. As metabolomic analysis demands high sensitivity for detecting metabolites present in low concentrations in biological samples, high-resolution power for identifying the metabolites and wide dynamic range to detect metabolites with variable concentrations in complex matrices, mass spectrometry is being the most extensively used analytical technique for fulfilling these requirements. Mass spectrometry alone can be used in a metabolomic analysis; however, some issues such as ion suppression may difficultate the quantification/identification of metabolites with lower concentrations or some metabolite classes that do not ionise as well as others. The best choice is coupling separation techniques, such as gas or liquid chromatography, to mass spectrometry, in order to improve the sensitivity and resolution power of the analysis, besides obtaining extra information (retention time) that facilitates the identification of the metabolites, especially when considering untargeted metabolomic strategies. In this chapter, the main aspects of mass spectrometry (MS), liquid chromatography (LC) and gas chromatography (GC) are discussed, and recent clinical applications of LC-MS and GC-MS are also presented.
Assuntos
Cromatografia Líquida/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Massas/métodos , Metabolômica/métodos , HumanosRESUMO
Prostate cancer is one of the most prevalent types of cancer in male population. It is a hormone driven disease, especially in its initial phase. Hence, androgen deprivation therapy (ADT) is the major chemotherapeutic effort and novel AR inhibitors with improved pharmacological profiles are needed. In this report, a novel bioactive compound was selected and investigated using in silico and cell-based assays. Neq0502 compound was selective for the testosterone stimulated AR-dependent prostate cancer cell (LNCaP, GI50=22.4µM) when compared with unstimulated LNCaP or AR-insensitive (DU145 and PC-3) cell lines. Cell cycle arrest study provided the same profile for Neq0502 and the reference drug enzalutamide. Moreover, this compound is not cytotoxic for fibroblast Balb/C 3T3 clone A31 cells up to 250µM, with a good selectivity ratio (SI>11), which could be used in compound optimization effort to a novel therapeutic alternative.
Assuntos
Acetanilidas/farmacologia , Antineoplásicos/farmacologia , Simulação por Computador , Compostos Heterocíclicos com 3 Anéis/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Receptores Androgênicos/metabolismo , Células 3T3 , Acetanilidas/química , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Heterocíclicos com 3 Anéis/química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Relação Estrutura-AtividadeRESUMO
Objetivo: Avaliar in vitro a propriedade física de rugosidade superficial de dois tipos de revestimentos utilizados sobre o condicionador tecidual Dura Conditioner: o primer do silicone Quick Line e o primer com o silicone Quick Line. Sessenta corpos de prova do condicionador de tecido Dura Conditioner com as dimensões de 23x9x3 milímetros foram preparados de acordo com as normas dos fabricantes. Os revestimentos foram aplicados sobre a superfície de 40 corpos de prova enquanto 20 corpos de condicionador de tecido Dura Conditioner não receberam revestimento e formaram o grupo controle. Dos outros 40 corpos de prova do condicionador de tecido, 20 receberam o revestimento do primer do silicone Quick Line e 20 receberam o revestimento do primer, sobre o qual foi aplicado o silicone Quick Line. Todos os corpos de prova foram divididos em 2 grupos e armazenados em estufa a 37 graus centígrados, cada grupo por 7 e 14 respectivamente. Posteriormente, foram submetidos à leitura de rugosidade superficial em um rugosímetro. Os resultados foram submetidos à leitura de rugosidade superficial em um rugosímetro. Os resultados foram submetidos à análise de variância, sendo adotado um nível de significância de 0,05. Os corpos de prova que receberam apenas o revestimento de primer foram os que apresentaram em média a menor rugosidade superficial, estatisticamente significante, pós-escovação mecânica.Para se obter menor rugosidade superficial, a utilização do revestimento de primer apenas é a mais indicada.
ObjectiveThis in vitro study evaluated the physical property called superficial roughness,of two sealers used with the tissue conditioner Dura Conditioner®: the primer ofthe silicon Quick Line® and the primer with the silicon Quick Line®.MethodsSixty specimens of the tissue conditioner Dura Conditioner® (23 x 9 x 3 millimeters)were prepared according to the manufactures directions. Twenty of the tissueconditioner Dura Conditioner® were left without sealer and constituted the controlgroup. Sealers were applied on the surface of forty conditioner specimens, asfollows: Twenty were coated with the primer of the silicon Quick Line®; the othertwenty were coated with the primer and the silicon Quick Line®. All specimenswere separated in two groups, which were stored in water at 37°C for 7 and 14days and mechanically brushed for 777 and 1,554 cycles, respectively. Then, allspecimens were submitted to the reading of superficial roughness. Data from thetest were analysed statistically using analysis of variance it was performed, adoptinga significance level of p<0,05.ResultsAfter the mechanical brushing, the specimens that presented on average thesmallest superficial roughness, statistically significant, were the ones that hadbeen coated only with the primer.ConclusionFor small superficial roughness, the coat only with the primer is the best choice.
Assuntos
Materiais Dentários , Reembasadores de DentaduraRESUMO
Objetivos: apresentar os resultados obtidos com a paratireoidectomia (PTX) subtotal em pacientes com hiperparatireoidismo (HPT) secundário àinsuficiência renal crônica (IRC), enfocando a contribuição e as dificuldades técnicas da cirurgia. Pacientes e Métodos: no período de janeiro de 1998 ajunho de 2005 foram operados consecutivamente no Hospital Universitário Antonio Pedro, 33 pacientes renais crônicos portadores de HPT secundário. Ascirurgias foram realizadas pelo mesmo cirurgião e a mesma equipe de nefrologista se encarregou do controle pré e pós-operatório. Esse grupo foiconstituído por 19 homens e 14 mulheres com idade média de 40,5 (16/68) anos e todos se encontravam em tratamento dialítico regular, com tempo médiode diálise de 113 (20/189) meses. Além dos cuidados habituais, todos os pacientes receberam calcitriol após as três últimas sessões de diálise queantecederam a cirurgia. Resultados: os resultados mais expressivos se refletiram sobre o aparelho músculo-esquelético e foram muito significativas as remissões das queixas de dor ósteo-articular, fraqueza e prurido; as calcificações não vasculares foram reabsorvidas e sinais de remineralização ósseaforam identificados após a cirurgia. As complicações pós-operatórias mais freqüentes foram a rouquidão transitória (21%), a hiperpotassemia (12%) e osangramento pós-operatório (12%). Nesse grupo há uma recidiva comprovada e já reoperada e dois pacientes encontram-se em fase de investigação, por provável insucesso na cirurgia, já que o PTH continua elevado. Os resultados menos favoráveis foram mais freqüentes nos casos onde foram encontradas apenas três glândulas paratireóides. Não houve mortalidade operatória. Conclusões: a PTX subtotal pode ser realizada com segurança e é efetiva para a remissão de diversas manifestações do HPT secundário, desde que continuem sob rigoroso controle clínico para evitar possíveis recidivas por hiperplasia do resíduo glandular.
Objective: to report the results obtained with subtotal parathyroidectomy (PTX) in patients with hyperparathyroidism (HPT) secondary to chronic renaldisease (CRD), focusing on the contribution and technical difficulties of the surgery. Methods: From January of 1998 to June of 2005, thirty-three end-stagerenal disease (ESRD) patients consecutively underwent PTX in the university hospital. Their mean age was 40.5 years; Nineteen were male, and 14 female.Mean time on dialysis was 113 months. Surgeries were accomplished by the same surgeon and the same nephrologist was in charge of the pre- andpostoperative care of the whole patients. Among the clinical manifestations those related to the osteopathy were the most prevalent ones. All patientsunderwent preoperative care and received calcitriol after the last three dialysis sessions that preceded the surgery. Results: the most expressiveimprovements pertained to the muscle-skeletal system. The alleviation of bone pain, joint pain, muscle weakness and itch were marked. Extra-vascularcalcifications were reabsorbed and radiological signs of bone remineralization were identified after the surgery. The most frequent postoperativecomplications were temporary hoarseness (21%), hyperkalemia (12%), and postoperative bleeding (12%). So far, we have faced one proven recurrencethat was managed by a surgical reintervention. In addition, PTH continues to be high in two patients who are undergoing prepare for a new surgery. Bad results seemed to be more frequent on patients in which only three parathyroid glands were found during the operation. Surgery was not associated to fatalities. Conclusions: subtotal PTX can be accomplished with safety in ESRD patients being effective for the alleviation of several manifestations of the secondary HPT. Patients should be maintained under strict clinical control to monitor for recurrences due to hyperplasia of the residual glandular tissue.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Doenças das Paratireoides/cirurgia , Doenças das Paratireoides/terapia , Falência Renal Crônica/complicações , ParatireoidectomiaRESUMO
BACKGROUND: The histologic patterns of bone disease, as well as the evolution of renal osteodystrophy after kidney transplantation (Tx), are not well defined. Information in this regard is scarce and contradictory. METHODS: Before and 6 months after Tx, analysis of biochemical, hormonal, and bone histomorphometric parameters were performed. Twenty patients (14 men and 6 women) entered the study. Median age was 36.5 (range, 20 to 55) years, and median time on dialysis was 22 (9 to 88) months. RESULTS: Bone histomorphometric diagnoses at pre-Tx were adynamic bone disease, 12; mixed bone disease, 3; mild disease, 3; and osteitis fibrosa, 2. After Tx, 11 had adynamic bone disease; 8, mild disease; and 1, osteomalacia. As a whole, dynamic parameters improved significantly in patients who had adynamic bone. Five of the 12 with this diagnosis completely recovered their bone turnover. Pre-Tx hyperparathyroidism bone features improved or resolved, but 5 of the 8 patients had low-turnover bone disease (adynamic disease, 4; osteomalacia, 1). Three of them had persistence of aluminum and/or iron deposits on bone surface, and the other 2 had hypophosphatemia and high intact parathyroid hormone levels. Overall, biochemical parameters tended toward normalization. Serum intact parathyroid hormone before Tx was correlated negatively with post-Tx trabecular thickness. CONCLUSION: Six months after Tx, bone histology remained abnormal. The high turnover bone disease improved in all cases, but in most of them low turnover bone disease emerged. Nearly half of the cases with pre-Tx adynamic bone disease recovered their bone turnover completely with some improvement observed in the majority of the remaining cases.
Assuntos
Doenças Ósseas/etiologia , Doenças Ósseas/patologia , Transplante de Rim , Adulto , Biópsia , Análise Química do Sangue , Osso e Ossos/patologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/patologia , Feminino , Humanos , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Estudos Longitudinais , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The prevalence of the types of renal osteodystrophy (ROD) has changed in the last two decades. This study evaluates the prevalence and determining factors of the types of ROD in two countries in South America. METHODS: Symptomatic patients who underwent bone biopsies for diagnostic purposes (1985 through 2001) were included in the study. In Brazil, a total of 2340 patients were reviewed, 93.1% on hemodialysis (HD), and 6.9% on continuous ambulatory peritoneal dialysis (CAPD). In Uruguay, 167 patients on hemodialysis were included. Uncalcified bone samples were analyzed in order to diagnose the different types of ROD. RESULTS: Comparing the 1980s to the 1990s, the prevalence of Brazilian patients with hyperparathyroid bone disease (HP) increased from 32.3% to 44.0%, while Al overload decreased from 61.3% to 42.4%. A logistic regression analysis showed that the main factors associated with HP included female gender, age of less than 40 years, black patients, longer time on dialysis, and absence of Al overload. In Uruguay, HP also increased over time from 31.8% to 70.5% (P < 0.05), while Al overload decreased from 42% to 27% (P < 0.05). CONCLUSION: A better control of Al overload may lead to a change in histologic pattern, as evidenced by the increasing prevalence of HP.
Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/epidemiologia , Adulto , Idoso , Osso e Ossos/patologia , Brasil/epidemiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/patologia , Feminino , Humanos , Hiperparatireoidismo/complicações , Hiperparatireoidismo/patologia , Ílio/patologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Fatores de Risco , Uruguai/epidemiologiaRESUMO
Um transplante renal bem sucedido pode corrigir a maioria das anormalidades metabólicas que causam a osteodistrofia renal. Porém, crescentes evidências mostram que a doença óssea pode constituir um importante problema clínico após o transplante renal. Neste estudo, avaliou-se, prospectivamente, a evolução da doença óssea através da análise da histomorfometria óssea e de parâmetros laboratoriais de pacientes antes e após seis meses de um transplante renal bem sucedido. Ao todo, 25 pacientes (18M/7F), com idade mediana de 37 anos (20-58), foram incluídos no estudo. Vinte e três estavam em hemodiálise e 2, em CAPD; a duração mediana em diálise foi de 23 meses (9-88). Análise histomorfométrica das biópsias ósseas foi obtida em 20 pacientes. No pré-Tx, doze apresentavam doença adinâmica, 3, lesão mínima, 3, doença mista e 2, osteíte fibrosa. No pós-Tx, onze apresentavam doença adinâmica, 8, lesão mínima e 1, osteomalácía. Apesar de termos encontrado uma freqüência de doença óssea adinâmica comparável no pré e no pós-Tx, os pacientes acometidos nas 2 fases do estudo não eram exatamente os mesmos. Dos 12 casos de doença adinâmica no pré-Tx, 5 melhoraram a formação e mineralização óssea passando a lesão mínima, e sete, permaneceram como doença óssea adinâmica. Os pacientes com lesões relacionadas ao hiperparatireoidismo evoluíram com melhora ou resolução completa dessas alterações. Entretanto, cinco evoluíram com doenças de baixo turnover ósseo (4 com doença adinâmica e 1 com osteomalácia). Três dos 4 pacientes que evoluíram como adinâmicos apresentavam persistência dos depósitos de alumínio e/ou ferro em suas superfícies ósseas. 0 outro e aquele com osteomalácia apresentavam hipofosfatemia e PTHi elevado. Os parâmetros laboratoriais também tiveram uma tendência à normalização. Os dois únicos pacientes hipercalcêmicos no pós-Tx apresentavam doença óssea de baixo turnover. Após o Tx, o nível do magnésio caiu e o do cloro, aumentou. Os pacientes com valores normais de fosfatase alcalina óssea no pré-Tx evoluíram com aumento significante deste parâmetro. Não houve correlação entre fosfatase alcalina óssea e PTHi no pós-Tx. O PTHi reduziu-se significantemente naqueles com valores iniciais aumentados, poreém, 4 persistiram com PTHi acima do normal. No pós-Tx, não houve correlação da fosfatase alcalina óssea ou do PTHi com qualquer dos parâmetros histomorfométricos...
Assuntos
Doenças Ósseas , Distúrbio Mineral e Ósseo na Doença Renal Crônica , Hiperparatireoidismo Secundário , Hipofosfatemia , Imunossupressores , Transplante de RimRESUMO
Os autores discutem a utilizaçäo de parafusos reabsorvíveis para fixaçäo interna rígida em cirurgia ortognática, apresentando um caso clínico de correçäo de uma deformidade dentofacial do tipo prognatismo mandibular. Foram analisados os polímeros sintéticos mais usados na formaçäo desses novos materiais reabsorvíveis, bem como suas propriedades, determinando-se as vantagens da sua utilizaçäo