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Herein we report an unprecedented and efficient methodology for accessing 6-alkoxy-Δ4,6-diene-3-one derivatives. Such scaffolds were serendipitously obtained in the course of the study of the reaction of Δ4-3-keto steroids with catalytic amounts of iodine in refluxing methanol. A series of 6-methoxy and 6-ethoxy- Δ4,6-diene-3-ones were prepared from easily-available sterols in a two-step sequence; first, oxidation of sterols furnished the Δ4-3-keto steroids, which were then refluxed with ethanol or methanol with I2 as catalyst to obtain a series of ten derivatives. Furthermore, this protocol was also effective for the introduction of a larger carbon chain at C-6. Druglikeliness properties of synthesized compounds were predicted using the SwissADME tool.
Assuntos
Fitosteróis , Esteróis , Metanol , EsteroidesRESUMO
Objetivo: Implementación en el sistema informático de laboratorio (SIL) de un algoritmo bioquímico automatizado para la identificación en analíticas de rutina de pacientes con dislipemia aterogénica y derivación prioritaria a la unidad de día de diabetes. Material y métodos: Se diseñó en el SIL el algoritmo: HBA1c>9,3 +TG>150mg/dl +cHDL <40mg/dl +LDL/ApoB es<1,3. Se inserta un comentario alertando al médico peticionario del diagnóstico de dislipemia aterogénica y se procede a la derivación prioritaria desde el laboratorio a la unidad de día de diabetes en los casos necesarios. Resultados: En el periodo de un año se han identificado a un total de 899 pacientes con HBA1c>7 y criterio de dislipemia aterogénica. De ellos, 203 pacientes procedentes de atención primaria con HbA1c>9,3 se derivaron al hospital de día de diabetes. Conclusiones: El refuerzo de la prevención cardiovascular es necesario a todos los niveles. El laboratorio clínico debe jugar un papel fundamental en el diagnóstico de las dislipemias. La detección temprana de los pacientes con alto riesgo cardiovascular es primordial y la colaboración entre las distintas unidades clínicas es fundamental para garantizar la seguridad del paciente.(AU)
Introduction: SmartLab 2.0 is an innovative concept of multidisciplinary collaboration between the clinical laboratory and the diabetes day unit that was born with the aim of identifying patients at high cardiovascular risk who require priority attention, such as patients with atherogenic dyslipidemia, in order to create a cardiovascular prevention strategy. Objective: Implementation in the Laboratory Information System (LIS) of an automated biochemical algorithm for the identification of patients with atherogenic dyslipidemia in routine analyses and priority referral to the diabetes day unit. Material and methods: The algorithm designed in the SIL was: HBA1c>9.3 +TG>150mg/dl +HDLc<40mg/dl +LDL/ApoB<1.3. A comment was inserted alerting the requesting physician of the diagnosis of atherogenic dyslipidemia and priority referral was made from the laboratory to the diabetes day unit in the necessary cases. Results: In the 1-year period, a total of 899 patients with HBA1c>7 and atherogenic dyslipidemia criteria were identified. Of these, 203 patients from primary care with HbA1c>9.3 were referred to the diabetes day hospital. Conclusions: Reinforcement of cardiovascular prevention is necessary at all levels. The clinical laboratory should play a fundamental role in the diagnosis of dyslipidemias. Early detection of patients at high cardiovascular risk is essential and collaboration between the different clinical units is fundamental to guarantee patient safety.(AU)
Assuntos
Humanos , Hiperlipidemias , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus , Alerta RápidoRESUMO
INTRODUCTION: SmartLab 2.0 is an innovative concept of multidisciplinary collaboration between the clinical laboratory and the diabetes day unit that was born with the aim of identifying patients at high cardiovascular risk who require priority attention, such as patients with atherogenic dyslipidemia, in order to create a cardiovascular prevention strategy. OBJECTIVE: Implementation in the Laboratory Information System (LIS) of an automated biochemical algorithm for the identification of patients with atherogenic dyslipidemia in routine analyses and priority referral to the diabetes day unit. MATERIAL AND METHODS: The algorithm designed in the SIL was: HBA1c>9.3 +TG>150mg/dl +HDLc<40mg/dl +LDL/ApoB<1.3. A comment was inserted alerting the requesting physician of the diagnosis of atherogenic dyslipidemia and priority referral was made from the laboratory to the diabetes day unit in the necessary cases. RESULTS: In the 1-year period, a total of 899 patients with HBA1c>7 and atherogenic dyslipidemia criteria were identified. Of these, 203 patients from primary care with HbA1c>9.3 were referred to the diabetes day hospital. CONCLUSIONS: Reinforcement of cardiovascular prevention is necessary at all levels. The clinical laboratory should play a fundamental role in the diagnosis of dyslipidemias. Early detection of patients at high cardiovascular risk is essential and collaboration between the different clinical units is fundamental to guarantee patient safety.
Assuntos
Aterosclerose , Doenças Cardiovasculares , Diabetes Mellitus , Dislipidemias , Humanos , Fatores de Risco , Hemoglobinas Glicadas , Aterosclerose/diagnóstico , Dislipidemias/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controleRESUMO
Circulating osteogenic precursor (COP) cells are peripheral blood cells with a capacity for osteogenesis. The objective of our study was to ascertain the percentage of COPs as an early biomarker of osteoporosis and the effect of these cells in response to Denosumab (DmAb) (anti-resorptive) or to Teriparatide (TPDP) (anabolic) as very effective drugs in the treatment of the illness. A first study was conducted on healthy volunteers, with three age ranges, to determine the percentage of COPs and relate it to their anthropometric and biochemical characteristics, followed by a second longitudinal study on patients with osteoporosis, whereby one group of patients was treated with TPTD and another with DmAb. All were analyzed by cytometry for COP percentage in blood, bone turnover markers, and bone mass. Our findings show that COPs are influenced by age and become more prolific in the stages of growth and skeletal maturation. A higher percentage of COPs is found in osteoporotic disease, which could constitute a predictive marker thereof. We also show how treatment with TPTD or DmAb mobilizes circulating osteogenic precursors in the blood. Significant increases in % COPs were observed after 12 months of treatment with Dmb (21.9%) and TPTD (17%). These results can be related to an increase in osteogenesis and, consequently, a better and more efficient repair of bone tissue.
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Liver is an essential organ that carries out multiple functions such as glycogen storage, the synthesis of plasma proteins, and the detoxification of xenobiotics. Hepatocytes are the parenchyma that sustain almost all the functions supported by this organ. Hepatocytes and non-parenchymal cells respond to the mechanical alterations that occur in the extracellular matrix (ECM) caused by organogenesis and regenerating processes. Rearrangements of the ECM modify the composition and mechanical properties that result in specific dedifferentiation programs inside the hepatic cells. Quiescent hepatocytes are embedded in the soft ECM, which contains an important concentration of fibrillar collagens in combination with a basement membrane-associated matrix (BM). This work aims to evaluate the role of fibrillar collagens and BM on actin cytoskeleton organization and the function of rat primary hepatocytes cultured on soft elastic polyacrylamide hydrogels (PAA HGs). We used rat tail collagen type I and Matrigel® as references of fibrillar collagens and BM respectively and mixed different percentages of collagen type I in combination with BM. We also used peptides obtained from decellularized liver matrices (dECM). Remarkably, hepatocytes showed a poor adhesion in the absence of collagen on soft PAA HGs. We demonstrated that collagen type I inhibited apoptosis and activated extracellular signal-regulated kinases 1/2 (ERK1/2) in primary hepatocytes cultured on soft hydrogels. Epidermal growth factor (EGF) was not able to rescue cell viability in conjugated BM but affected cell aggregation in soft PAA HGs conjugated with combinations of different proportions of collagen and BM. Interestingly, actin cytoskeleton was localized and preserved close to plasma membrane (cortical actin) and proximal to intercellular ducts (canaliculi-like structures) in soft conditions; however, albumin protein expression was not preserved, even though primary hepatocytes did not remodel their actin cytoskeleton significantly in soft conditions. This investigation highlights the important role of fibrillar collagens on soft hydrogels for the maintenance of survival and aggregation of the hepatocytes. Data suggest evaluating the conditions that allow the establishment of optimal biomimetic environments for physiology and cell biology studies, where the phenotype of primary cells may be preserved for longer periods of time.
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La malaria o paludismo es una patología causada por un parásito denominado Plasmodium, propia de países tropicales. Entre la sintomatología más frecuente destaca la malaria cerebral, ictericia, crisis convulsivas, anemia, hipoglucemia, fallo renal y acidosis metabólica, entre otras. Presentamos el caso de un paciente diagnosticado de paludismo, que presentó un cuadro de pancreatitis aguda necroticohemorrágica con mala evolución, como ejemplo inusual de dicha asociación descrita en nuestro país (AU)
Malaria is a pathology caused by a parasite called Plasmodium, characteristic of tropical countries. The most frequent symptomatology includes cerebral malaria, jaundice, convulsive crisis, anemia, hypoglycemia, kidney failure and metabolic asidosis, among others. We are presenting the case of a patient diagnosed with malaria who suffered from acute necrotizing hemorrhagic pancreatitis and evolved poorly, as an example of this combination of symptoms, rarely found in our country (AU)
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite Necrosante Aguda/complicações , Pancreatite Necrosante Aguda/terapia , Pancreatite Necrosante Aguda , Malária Falciparum/complicações , Endoscopia/instrumentação , Endoscopia/métodos , Ultrassonografia/instrumentação , Ultrassonografia/métodos , Ultrassonografia , Colecistite Acalculosa/complicações , Colecistite AcalculosaRESUMO
Malaria is a pathology caused by a parasite called Plasmodium, characteristic of tropical countries. The most frequent symptomatology includes cerebral malaria, jaundice, convulsive crisis, anemia, hypoglycemia, kidney failure and metabolic asidosis, among others. We are presenting the case of a patient diagnosed with malaria who suffered from acute necrotizing hemorrhagic pancreatitis and evolved poorly, as an example of this combination of symptoms, rarely found in our country.
Assuntos
Malária Falciparum/complicações , Pancreatite Necrosante Aguda/etiologia , Cuidados Críticos , Evolução Fatal , Humanos , Malária Falciparum/diagnóstico por imagem , Malária Falciparum/parasitologia , Masculino , Pessoa de Meia-Idade , Pancreatite Necrosante Aguda/diagnóstico por imagem , Pancreatite Necrosante Aguda/parasitologia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To determine pre-/intraoperative risk factors for anastomotic leak after colon resection for cancer and to create a practical instrument for predicting anastomotic leak risk. BACKGROUND: Anastomotic leak is still the most dreaded complication in colorectal surgery. Many risk factors have been identified to date, but multicentric prospective studies on anastomotic leak after colon resection are lacking. METHODS: Fifty-two hospitals participated in this prospective, observational study. Data of 3193 patients, operated for colon cancer with primary anastomosis without stoma, were included in a prospective online database (September 2011-September 2012). Forty-two pre-/intraoperative variables, related to patient, tumor, surgical procedure, and hospital, were analyzed as potential independent risk factors for anastomotic leak (60-day follow-up). A nomogram was created to easily predict the risk of anastomotic leak for a given patient. RESULTS: The anastomotic leak rate was 8.7%, and widely varied between hospitals (variance of 0.24 on the logit scale). Anastomotic leak significantly increased mortality (15.2% vs 1.9% in patients without anastomotic leak, P < 0.0001) and length of hospitalization (median 23 vs 7 days in uncomplicated patients, P < 0.0001). In the multivariate analysis, the following variables were independent risk factors for anastomotic leak: obesity [P = 0.003, odds ratio (OR) = 2.7], preoperative serum total proteins (P = 0.03, OR = 0.7 per g/dL), male sex (P = 0.03, OR = 1.6), ongoing anticoagulant treatment (P = 0.05, OR = 1.8), intraoperative complication (P = 0.03, OR = 2.2), and number of hospital beds (P = 0.04, OR = 0.95 per 100 beds). CONCLUSIONS: Anastomotic leak after colon resection for cancer is a frequent, relevant complication. Patients, surgical technique, and hospital are all important determining factors of anastomotic leak risk.
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Fístula Anastomótica/epidemiologia , Colectomia/efeitos adversos , Neoplasias do Colo/cirurgia , Idoso , Idoso de 80 Anos ou mais , Fístula Anastomótica/diagnóstico , Fístula Anastomótica/terapia , Neoplasias do Colo/complicações , Neoplasias do Colo/patologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nomogramas , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologiaRESUMO
Introducción La hemorragia intracerebral (HIC) espontánea se asocia a una mortalidad que oscila entre el 40 y el 50% de los casos. Entre los supervivientes, únicamente el 10% serán independientes al mes, sin que exista ningún tratamiento eficaz de las secuelas, a excepción de las escasas posibilidades que aporta la rehabilitación. Objetivos En este artículo llamamos la atención acerca de las perspectivas que puede tener el trasplante intracerebral de células madre mesenquimales (CMM) de médula ósea como un posible tratamiento de las secuelas neurológicas producidas tras una HIC experimental. Material y métodos Describimos un modelo experimental de HIC, utilizando la administración intracerebral de colagenasa IV a nivel de ganglios basales en la rata Wistar. Los déficits neurológicos provocados por la HIC pueden ser cuantificados a lo largo de los meses siguientes mediante diversos test de valoración funcional (mNSS, Rota-rod, VTB-test). En un estudio previamente publicado, hemos aplicado este modelo a 10 animales que recibieron intracerebralmente 5×10CMM alogénicas, en 10μl de suero fisiológico, a los 2 meses de la HIC, mientras que en (..) (AU)
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Humanos , Terapia Baseada em Transplante de Células e Tecidos , Acidente Vascular Cerebral/complicações , Hemorragia Cerebral/complicações , Células-Tronco Neurais/transplante , NeurogêneseRESUMO
INTRODUCTION: Spontaneous intracerebral hemorrhage (ICH) is associated with mortality between 40 and 50% of cases. Among the survivors, only 10% are independent after one month, there is no effective treatment of sequelae, except for the limited possibilities providing for rehabilitation. OBJECTIVES: We review the current experience with intracerebral transplantation of mesenchymal stem cells (MSCs) obtained from bone marrow as a potential treatment of neurological sequelae occurring after experimental ICH. MATERIAL AND METHODS: We describe the model of ICH by intracerebral administration of collagenaseIV at basal ganglia level in Wistar rats. Neurological deficits caused by ICH can be quantified through a variety of functional assessment test (NMSS, Rota-rod, VTB-test). 5×10allogeneic MSCs in 10µl of saline were administered intracerebrally in 10 animals, 2 months after ICH. In another 10 animals (controls) the same volume of saline was administered. Changes in the functional deficits were assessed during the next 6 months in both experimental groups. RESULTS: The results suggested therapeutic efficacy of MSCs transplantation and showed that transplanted stem cells can survive in the injured brain, transforming into neurons and glial cells. This form of cell therapy induces reactivation of endogenous neurogenesis at the subventricular zone (SVZ) and achieves antiapoptotic protective effect in the injured brain. CONCLUSIONS: Cell therapy represents an important field of research with potential clinical application to treatment of neurological sequels, currently considered irreversible. Neurosurgeons should become involved in the development of these new techniques that are likely to shape the future of this specialty.
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Terapia Baseada em Transplante de Células e Tecidos , Modelos Animais de Doenças , Animais , Hemorragia Cerebral , Humanos , Transplante de Células-Tronco Mesenquimais , Ratos Wistar , Acidente Vascular CerebralRESUMO
It has been previously showed that fructose-1,6-bisphosphate (FBP) has anti-inflammatory and immunomodulatory effects on several experimental inflammation models. However, the effects and mechanism of FBP on Zymosan-induced acute lung injury (ALI) in mice had not been tested. In this study, our aim was to assess the anti-inflammatory activities of FBP on Zymosan-induced ALI. We found that in vivo treatment with FBP (500 mg/kg i.p.) markedly decreased the nitric oxide (NO) levels in the lungs and significantly reduced bronchoalveolar lavage fluid total cell and neutrophil counts and protein exudation after Zymosan challenge. Furthermore, FBP inhibited inducible nitric oxide synthase (iNOS) activities in RAW macrophages. Meanwhile, FBP did not inhibit the cyclooxigenase 2, interleukin-6, and nuclear factor kappa B transcription. Taken together, these results suggest that FBP shows anti-inflammatory effects through inhibiting lung edema, NO, and iNOS activities.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Frutosedifosfatos/farmacologia , Óxido Nítrico Sintase Tipo II/biossíntese , Óxido Nítrico/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Ciclo-Oxigenase 2/biossíntese , Ciclo-Oxigenase 2/genética , Edema/tratamento farmacológico , Edema/imunologia , Edema/patologia , Frutosedifosfatos/uso terapêutico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Interleucina-6/biossíntese , Interleucina-6/genética , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Macrófagos/metabolismo , Masculino , Camundongos , NF-kappa B/biossíntese , NF-kappa B/genética , Neutrófilos , Óxido Nítrico Sintase Tipo II/metabolismo , Transcrição Gênica , ZimosanRESUMO
Due to the fact that an increased number of patients have experienced bloodstream infections caused by Candida species and the high mortality of this infection, there is a need for a strategy to reduce this scenery. One possible strategy is the use of new drugs, such as fructose-1,6-bisphosphate (FBP), which is a high-energy glycolytic metabolite and has shown to have therapeutic effects in several pathological conditions such as ischemia, shock, toxic injuries, and bacterial sepsis. The aim of this manuscript was to determine the role of FBP in experimental Candida albicans bloodstream infection. We used mice that were divided into three experimental groups: sham (not induced), bloodstream infection (induced with intratracheal instillation of C. albicans) and FBP (bloodstream infection plus FBP 500 mg/kg i.p.). Blood was taken for assessment of complete hematological profile and cytokine assay (IL-6 and MCP-1). Results of the study demonstrated that mortality decreased significantly in groups that received FBP. All cytokine and hematological indexes of FBP group were similar to bloodstream infection group with exception of platelets count. FBP significantly prevented the decrease in platelets. Taken together, our results demonstrate that FBP prevented the mortality in C. albicans bloodstream infection.
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Candidemia/tratamento farmacológico , Candidemia/mortalidade , Frutosedifosfatos/uso terapêutico , Contagem de Plaquetas , Animais , Candida albicans/efeitos dos fármacos , Candidemia/sangue , Candidemia/microbiologia , Quimiocina CCL2/sangue , Frutosedifosfatos/farmacologia , Interleucina-6/sangue , Masculino , CamundongosRESUMO
Zymosan is a yeast cell wall particle that activates several cell lines, especially macrophages, resulting in the stimulated secretion of inflammatory products including tumor necrosis factor alpha (TNF-α) and arachidonic acid. Cyclooxygenase-2 (COX-2) is an immediate early gene induced by several stimuli in macrophages. The following research aimed to investigate the regions of COX-2 promoter gene that mediate the inductive effects of zymosan. Transient transfections with a series of COX-2 promoter-mutation constructs were performed to further elucidate the effects of zymosan on COX-2 transcription. Exposure to zymosan (50 µg/mL for 24 h) markedly enhanced the relative luciferase activity in RAW 264.7 macrophages (mouse leukemic monocyte macrophage cell line) transfected with COX-2 luciferase promoter constructs. Deletion on the CCAAT-enhancer binding protein (C/EBP) and nuclear factor kappa B (NF-kappa B) binding site resulted in an important decrease in reporter gene activity and a deletion of NF-kappa B and C/EBP with mutation of the cyclic adenosine monophosphate response element (CRE) and/or activator protein-1 totally abolished the reporter gene activity induced by zymosan. These findings provide further insight into the signal transduction pathways involved in COX-2 gene activated by zymosan in macrophages.
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Ciclo-Oxigenase 2/genética , Macrófagos/metabolismo , Ativação Transcricional , Zimosan/farmacologia , Animais , Sítios de Ligação , Proteínas Estimuladoras de Ligação a CCAAT , Linhagem Celular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Macrófagos/efeitos dos fármacos , Camundongos , NF-kappa B , Regiões Promotoras Genéticas , Transdução de Sinais , Fator de Transcrição AP-1RESUMO
Human respiratory syncytial virus (HRSV) is the most common cause of severe respiratory infections in infants and young children, often leading to hospitalization. In addition, HRSV poses a serious health risk in immunocompromised individuals and the elderly. It has been reported that this virus can infect mouse antigen-presenting cells, including B lymphocytes. In these B cells, HRSV infection upregulates the expression of activation markers, including MHC class II and CD86, but not MHC class I molecules. Here, we report that HRSV infection of spleen B lymphocytes downregulated TLR4. Either blocking with anti-TLR4 antibody or genetic deletion, but not functional deficiency of TLR4, moderately reduced the infectivity of HRSV in B lymphocytes. HRSV-infected B lymphocytes with deleted TLR4 upregulated MHC class II and CD86 molecules to the same levels as TLR4(+) wild type B cells. Since the activation of monocytes and macrophages by HRSV was previously reported to depend on TLR4, the current study indicates that these cells and B lymphocytes respond to HRSV infection with different activation pathways.
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Linfócitos B/imunologia , Ativação Linfocitária/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Receptor 4 Toll-Like/imunologia , Animais , Linfócitos B/metabolismo , Linfócitos B/virologia , Antígeno B7-2/imunologia , Antígeno B7-2/metabolismo , Separação Celular , Células Cultivadas , Feminino , Citometria de Fluxo , Antígenos de Histocompatibilidade Classe II/imunologia , Antígenos de Histocompatibilidade Classe II/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Camundongos , Camundongos Knockout , Vírus Sincicial Respiratório Humano/fisiologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Regulação para CimaRESUMO
La lipoproteína (a) (Lp[a]) es una lipoproteína esférica, rica en ésteres de colesterol y fosfolípidos con una apolipoproteína a que se asemeja estructuralmente a la molécula de lipoproteínas de baja densidad (LDL). Los valores elevados de Lp(a) se asocian a ataques cardíacos, apoplejías, estrechamiento de las arterias y reestenosis de vasos después de haber establecido quirúrgicamente un puente coronario. El hecho que la concentración de Lp(a) no pueda modificarse con los hipolipemiantes habituales influye en el cumplimiento terapéutico de los pacientes, ya que el porcentaje de colesterol transportado por la Lp(a) es inmodificable, y éste puede llegar a concentraciones de hasta 80-90 mg/dl. Objetivos: Estudiar si los valores de Lp(a) influyen en la consecución de los objetivos terapéuticos y, en caso afirmativo, analizar las posibles alternativas. Pacientes y métodos: Se seleccionó a una población de 100 pacientes intervenidos de bypass aortocoronario. Todos los pacientes fueron pesados y tallados, se les tomó la presión arterial y el perímetro de cintura, se les determinó un hemograma, coagulación, perfil tiroideo, bioquímica general y un perfil de riesgo cardiovascular. Resultados: Dividimos a los pacientes en función de la concentración de Lp(a) al año de seguimiento. Según los valores de Lp(a) el cumplimiento es del 46,55% para Lp(a) < 30 mg/dl y del 35,75% para Lp (a) > 30 mg/dl. Si aplicamos el LDL corregido (colesterol unido a LDL colesterol unido a Lp[a]) el cumplimiento en el grupo de mayor riesgo se incrementa en un 39,89%, pasando al 75,60%. Conclusiones: Confirmamos que la consecución de los objetivos terapéuticos de los pacientes puede mejorarse con un seguimiento de éstos de manera más intensiva y que esta consecución está influida por la elevación de las concentraciones de Lp(a), con lo que se confirma un cumplimiento más bajo en los pacientes con riesgo mayor en función de sus concentraciones de Lp(a) (AU)
Lipoprotein(a) (Lp[a]) is a spherical lipoprotein, rich in cholesterol esters and phospholipids, with an apolipoprotein structurally similar to the LDL molecule. Elevated LP(a) levels are associated with heart attacks, stroke, narrowing of the arteries and restenosis of vessels after coronary bypass surgery. Lp(a) concentrations cannot be modified by routine lipid-lowering therapy and consequently this lipoprotein will influence the achievement of therapeutic targets. The proportion of cholesterol carried by Lp(a) is unchangeable and can reach concentrations of up to 80-90 mg / dl. Objectives: To study the influence of Lp(a) levels on the achievement of therapeutic LDL-cholesterol targets in high cardiovascular risk patients and to analyze the possible alternatives. Patients and methods: We selected a population of 100 patients undergoing aortocoronary bypass. In all patients, weight, height, blood pressure and waist perimeter were measured. Hemogram, coagulation parameters, thyroid profile, general biochemistry and cardiovascular risk profile were also determined. Results: Patients were divided according to Lp(a) concentrations at 1 year of follow-up. According to Lp(a) values, therapeutic LDL-cholesterol targets were achieved by 46.55% of patients with Lp(a) < 30 mg/dl and by 35.71% of those with Lp(a) > 30 mg/dl. When corrected LDL (LDL-c - Lp(a)-c) was applied, achievement of therapeutic targets increased by 39.89% in the group at highest risk, representing 75.60% of this group. Conclusions: We confirm that reaching therapeutic LDL-cholesterol targets can be improved by more intensive follow-up. Achievement of targets is influenced by rising concentrations of Lp(a), confirming that targets are harder to achieve in patients whose Lp(a) profile confers higher risk (AU)
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Humanos , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/sangue , Ponte de Artéria Coronária , LDL-Colesterol/sangue , Seguimentos , Fatores de RiscoRESUMO
BACKGROUND AIMS: Cord blood (CB) transplants with co-infusion of third-party donor (TPD) mobilized hematopoietic stem cells (MHSC) have been shown to result in 'bridge' engraftment with prompt neutrophil recovery and high final rates of CB engraftment and full chimerism. This strategy overcomes the limitation posed by low cellularity of CB units for unrelated transplants in adults. Enhancement of adaptive immunity reconstitution without increasing risks of graft-versus-host disease (GvHD) is required to optimize results further. Our objectives were to evaluate co-infusion of mesenchymal stromal cells (MSC) from the same TPD regarding tolerance, CB engraftment and effects on acute (a)GvHD, both preventive and therapeutic. METHODS: Ex vivo-expanded bone marrow MSC were infused at the time of the transplant or the in case of refractory aGvHD. RESULTS: Nine patients received 1.04 - 2.15 x 10(6)/kg (median 1.20) MSC immediately after CB and TPD MHSC. Neither immediate adverse side-effects nor significant differences regarding CB engraftment or aGvHD development were observed. Four patients developed grade II aGvHD, refractory to steroids in two. These reached complete remission after therapeutic infusions of MSC. CONCLUSIONS: In recipients of 'dual CB/TPD MHSC transplants', MSC infusions were therapeutically effective for severe aGvHD but no significant differences in CB engraftment and incidence of severe aGvHD were observed following their prophylactic use. Although results of this study alone cannot conclusively determine the application of MSC in CB transplantation, we believe that, in this setting, the best use of MSC could be as pre-emptive treatment for aGvHD.
Assuntos
Doença Enxerto-Hospedeiro/imunologia , Neoplasias Hematológicas/terapia , Células-Tronco Mesenquimais/metabolismo , Indução de Remissão , Células Estromais/metabolismo , Doença Aguda , Adulto , Medula Óssea/metabolismo , Contagem de Células , Quimerismo , Feminino , Sangue Fetal/citologia , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/imunologia , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/imunologia , Pessoa de Meia-Idade , Neutrófilos/imunologia , Neutrófilos/patologia , Projetos Piloto , Células Estromais/citologia , Células Estromais/imunologia , Doadores de Tecidos , Transplante HomólogoRESUMO
Introducción. La revascularización miocárdica es una intervención terapéutica perfectamente establecida en pacientes con enfermedad coronaria. El objetivo del presente estudio es el de comprobar el cumplimiento terapéutico de los objetivos marcados por el Adult Treatment Panel (ATP) III para una población de muy alto riesgo cardiovascular y la evolución de los principales factores de riesgo cardiovascular. Material y métodos. Se han estudiado un total de 131 pacientes intervenidos de bypass aortocoronario. Para la evaluación de su riesgo y posterior tratamiento, fueron atendidos a los 3, 6 y 12 meses tras la intervención. Independientemente de otros datos necesarios para la historia clínica, a todos se les determinó los valores de presión arterial, perímetro de cintura, peso, talla e índice de masa corporal, hábito tabáquico y hemograma, un perfil bioquímico y un perfil de riesgo cardiovascular que incluye, además de los habituales, una ultracentrifugación para la separación de las lipoproteínas, los valores de apolipoproteína (apo) A-I y B-100 y diversos marcadores de riesgo e inflamación como la lipoproteína(a) (Lp[a]), proteína C reactiva ultrasensible (PCR), el fibrinógeno y la homocisteína. Resultados. Los valores de colesterol unido a lipoproteínas de baja densidad (cLDL) descendieron desde 142 a 108 mg/dl y los de apo B desde 101 a 79 mg/dl. El 44% de los pacientes cumplió los objetivos marcados por el ATP III, es decir, cLDL 102 cm, presente en el 50% de los pacientes, descendió al 19,64%, y los fumadores, que abarcaban el 58% de los pacientes, abandonaron en su totalidad el hábito tabáquico. Conclusiones. Tras el tratamiento con estatinas y/o estatinas-ezetimiba y modificación de los hábitos de vida, los pacientes experimentan una reducción significativa de los principales factores de riesgo a excepción de la homocisteína y de la Lp(a); el 44% de los pacientes estudiados cumple los objetivos marcados por el ATP III. Por otro lado, el tratamiento combinado estatina-ezetimiba parece producir mayores beneficios que el tratamiento con estatinas en monoterapia (AU)
Introduction. Myocardial revascularization is a well established therapeutic intervention in coronary disease. The aim of the present study was to asses the achievement of the therapeutic goals recommended by the Adult Treatment Panel (ATP) III in patients with high risk for cardiovascular disease. Material and methods. We have studied 131 patients with a previous aorto-coronary bypass. In order to evaluate their cardiovascular risk and their pharmacological treatment, we have followed the patients 3, 6 and 12 months after the intervention. In addition to the medical history, we measured blood pressure, waist circumference, weight, height, body mass index (BMI), smokers, non smokers, haematology test, biochemical and cardiovascular profile. To complete the cardiovascular study we determined cholesterol fractions. The serum samples were ultracentrifuged to separate lipoproteins, and measure the levels of apolipoproteins (Apo) A1 and B 100 and several markers of cardiovascular risk and inflammation such as lipoprotein (Lp) (a), ultra sensitive C reactive protein (CPR), fibrinogen and homocysteine. Results. The levels of lowdensity lipoprotein (LDL) decreased from 142 mg/dl to 108 mg/dl and Apo B levels from 101 mg/dl to 79 mg/dl. The therapeutic goals recommended by ATP III were achieved by 44% of patients, that is a cLDL < 100 mg/dL. We observed changes in other risk factors in our population study. The number of overweight patients decreased from 42% to 12%, and obese patients from 27% to 10%. Those patients with a waist circumference greater than 102 cm decreased from 50% to 19.64% and 58% of the smokers gave it up. Conclusions. The patients showed a significant reduction in the major risk factors with no changes in the homocysteine and Lp (a) levels. After treatment with statins and/or statins- ezetimibe) 44% of the patients achieved the therapeutic goals suggested by ATP III. The combined treatment (statins + ezetimibe) seems to be more effective than therapy with statins only (AU)