Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 80
Filter
1.
Sci Rep ; 13(1): 22403, 2023 12 16.
Article in English | MEDLINE | ID: mdl-38104230

ABSTRACT

Skeletogenesis and hematopoiesis are interdependent. Niches form between cells of both lineages where microenvironmental cues support specific lineage commitment. Because of the complex topography of bone marrow (BM), the identity and function of cells within specialized niches has not been fully elucidated. Dentin Matrix Protein 1 (DMP1)-Cre mice have been utilized in bone studies as mature osteoblasts and osteocytes express DMP1. DMP1 has been identified in CXCL12+ cells and an undefined CD45+ population. We crossed DMP1-Cre with Ai9 reporter mice and analyzed the tdTomato+ (tdT+) population in BM and secondary hematopoietic organs. CD45+tdT+ express myeloid markers including CD11b and are established early in ontogeny. CD45+tdT+ cells phagocytose, respond to LPS and are radioresistant. Depletion of macrophages caused a significant decrease in tdT+CD11b+ myeloid populations. A subset of CD45+tdT+ cells may be erythroid island macrophages (EIM) which are depleted after G-CSF treatment. tdT+CXCL12+ cells are in direct contact with F4/80 macrophages, express RANKL and form a niche with B220+ B cells. A population of resident cells within the thymus are tdT+ and express myeloid markers and RANKL. In conclusion, in addition to targeting osteoblast/osteocytes, DMP1-Cre labels unique cell populations of macrophage and stromal cells within BM and thymus niches and expresses key microenvironmental factors.


Subject(s)
Bone Marrow , Osteoblasts , Mice , Animals , Osteoblasts/metabolism , Osteocytes/metabolism , Stromal Cells , Bone Marrow Cells
2.
J Environ Radioact ; 246: 106831, 2022 May.
Article in English | MEDLINE | ID: mdl-35144201

ABSTRACT

10-years records of monthly bulk atmospheric fluxes of 7Be and 210Pb (wet + dry, n = 119 samples) at a coastal station in Cienfuegos (Cuba) between 2010 and 2019 were reported and assessed in function of their temporal variability and meteorological influence. Fluxes of 7Be and 210Pb ranged from 120 to 15617 and from 29 to 911 mBq m-2 day-1, respectively. Both radionuclides exhibited a similar seasonal trend with highest values during wet months and minimum values during dry months. The removal of 7Be and 210Pb from the atmosphere was mainly controlled by wet depositions, while dry deposition was estimated to be more important for 210Pb (29% of the total bulk deposition) than for 7Be (12%). The 210Pb/7Be ratios (average of 0.10) showed low variability during wet months with abrupt peaks in the driest months with low temperatures and the highest wind speed and pressure, which was mainly attributed to contributions from soil resuspension. The calculated total deposition velocity of aerosols derived from 7Be (average of 0.48 cm s-1) and 210Pb (average of 0.47 cm s-1) was in agreement with values reported in the literature. Multiple linear regression models for the monthly fluxes of 7Be and 210Pb based on precipitation, temperature and pressure and explaining about 60% of their variances were derived, highlighting the preponderant role of the local and regional conditions on the variability of these radionuclides. The annual fluxes of 7Be (209-1901 Bq m-2 y-1) and 210Pb (35-123 Bq m-2 y-1) were in the range of variations observed in other coastal stations worldwide, showing fluctuations affected by changes in the amount of precipitation during the wet periods. 7Be annual variability also evidenced a significant modulation with the solar activity.


Subject(s)
Air Pollutants, Radioactive , Air Pollutants , Radiation Monitoring , Air Pollutants/analysis , Air Pollutants, Radioactive/analysis , Atmosphere , Cuba , Environmental Monitoring , Lead , Radioisotopes/analysis
4.
Blood Adv ; 5(21): 4435-4446, 2021 11 09.
Article in English | MEDLINE | ID: mdl-34581760

ABSTRACT

Osteoclasts are multinuclear cells of monocytic lineage, with the ability to resorb bone. Studies in mouse have identified bone marrow clonal progenitors able to generate mature osteoclast cells (OCs) in vitro and in vivo. These osteoclast progenitors (OCPs) can also generate macrophages and dendritic cells. Interestingly, cells with equivalent potential can be detected in periphery. In humans, cells with OCP activity have been identified in bone marrow and periphery; however, their characterization has not been as extensive. We have developed reproducible methods to derive, from human pluripotent stem cells, a population containing monocyte progenitors able to generate functional OCs. Within this population, we have identified cells with monocyte and osteoclast progenitor activity based on CD11b and CD14 expression. A population double positive for CD11b and CD14 contains cells with expected osteoclastic potential. However, the double negative (DN) population, containing most of the hematopoietic progenitor activity, also presents a very high osteoclastic potential. These progenitor cells can also be differentiated to macrophage and dendritic cells. Further dissection within the DN population identified cells bearing the phenotype CD15-CD115+ as the population with highest monocytic progenitor and osteoclastic potential. When similar methodology was used to identify OCPs from human peripheral blood, we confirmed a published OCP population with the phenotype CD11b+CD14+. In addition, we identified a second population (CD14-CD11bloCD115+) with high monocytic progenitor activity that was also able to form osteoclast like cells, similar to the 2 populations identified from pluripotent stem cells.


Subject(s)
Osteoclasts , Pluripotent Stem Cells , Animals , Bone Marrow Cells , Cell Differentiation , Humans , Mice , Monocytes
6.
J Immunol ; 204(4): 868-878, 2020 02 15.
Article in English | MEDLINE | ID: mdl-31915261

ABSTRACT

Osteoclasts (OC) originate from either bone marrow (BM)-resident or circulating myeloid OC progenitors (OCP) expressing the receptor CX3CR1. Multiple lines of evidence argue that OCP in homeostasis and inflammation differ. We investigated the relative contributions of BM-resident and circulating OCP to osteoclastogenesis during homeostasis and fracture repair. Using CX3CR1-EGFP/TRAP tdTomato mice, we found CX3CR1 expression in mononuclear cells, but not in multinucleated TRAP+ OC. However, CX3CR1-expressing cells generated TRAP+ OC on bone within 5 d in CX3CR1CreERT2/Ai14 tdTomato reporter mice. To define the role that circulating cells play in osteoclastogenesis during homeostasis, we parabiosed TRAP tdTomato mice (CD45.2) on a C57BL/6 background with wild-type (WT) mice (CD45.1). Flow cytometry (CD45.1/45.2) demonstrated abundant blood cell mixing between parabionts after 2 wk. At 4 wk, there were numerous tdTomato+ OC in the femurs of TRAP tdTomato mice but almost none in WT mice. Similarly, cultured BM stimulated to form OC demonstrated multiple fluorescent OC in cell cultures from TRAP tdTomato mice, but not from WT mice. Finally, flow cytometry confirmed low-level engraftment of BM cells between parabionts but significant engraftment in the spleens. In contrast, during fracture repair, we found that circulating CX3CR1+ cells migrated to bone, lost expression of CX3CR1, and became OC. These data demonstrate that OCP, but not mature OC, express CX3CR1 during both homeostasis and fracture repair. We conclude that, in homeostasis mature OC derive predominantly from BM-resident OCP, whereas during fracture repair, circulating CX3CR1+ cells can become OC.

7.
Rev. medica electron ; 41(4): 862-878, jul.-ago. 2019. tab
Article in Spanish | LILACS, CUMED | ID: biblio-1094094

ABSTRACT

RESUMEN Introducción: las enfermedades cardiovasculares constituyen la principal causa de muerte en la mayoría de los países. Se describen los factores de riesgo para enfermedad coronaria como no modificables: edad, sexo y antecedentes familiares; y modificables relacionados al estilo de vida: tabaquismo, dislipidemia, obesidad, sedentarismo, diabetes, uso abusivo de alcohol y la enfermedad hipertensiva. Objetivo: caracterizar los factores de riesgo asociados a la cardiopatía isquémica en Atención Secundaria de Salud. Materiales y métodos: estudio observacional, descriptivo transversal en pacientes ingresados en el Hospital "Mártires del 9 de Abril" de Sagua la Grande, en el periodo comprendido entre los años 2016 y 2017. Integraron la muestra 96 pacientes que ingresaron con diagnóstico de cardiopatía isquémica. Se describieron las características demográficas de los mismos; fueron identificados los factores de riesgo y se determinó la frecuencia de asociación de otras formas clínicas de ateromatosis. Resultados: los pacientes fueron mayores de 60 años de edad; la mayoría tenían color de la piel blanca; presentaban antecedentes patológicos familiares de cardiopatía isquémica; las principales formas de cardiopatía isquémica fueron: angina e insuficiencia cardiaca; todos los pacientes presentaron uno o más factores de riesgo cardiovascular, los más significativos fueron, hipertensión arterial, tabaquismo aumento de la circunferencia abdominal y personalidad tipo "A". Conclusiones: la mayoría de los pacientes exhibieron alteraciones en el electrocardiograma: descenso del segmento ST, bloqueo de rama izquierda del haz de His y fibrilación auricular; se observó hipertrigliceridemia y se apreció asociación entre enfermedad renal crónica y angina.


ABSTRACT Introduction: cardiovascular diseases are the main cause of death in most of the countries. The risk factors for coronary disease are described as unmodifiable: age, sex and family history; and modifiable related to lifestyle: smoking, dyslipidemia, obesity, sedentary lifestyle, diabetes, abusive use of alcohol and hypertensive disease. Objective: to characterize the risk factors associated to ischemic heart disease in secondary health care. Material and methods: observational, cross-sectional, descriptive study in patients admitted in "Mártires del 9 de Abril" Hospital, Sagua la Grande, between 2016 and 2017. The sample consisted of 96 patients admitted with a diagnosis of ischemic heart disease. Their demographic characteristics were described; the risk factors were identified and the frequency of association of other clinical forms of atheromatosis was determined. Results: the patients were aged more than 60 years; most of them were white people and had family pathological antecedents of ischemic heart disease; the main forms of ischemic heart disease were angina and heart failure; all patients showed one or more cardiovascular risk factors being arterial hypertension, smoking, increase of abdominal circumference and type A personality the most significant ones. Conclusions: the majority of patients showed alterations in the electrocardiogram: ST segment decrease, His bundle left branch blockage and atrial fibrillation; hypertriglyceridemia was observed and there was an association between chronic kidney disease and angina.


Subject(s)
Humans , Aged , Tobacco Use Disorder/etiology , Risk Factors , Myocardial Ischemia/diagnosis , Myocardial Ischemia/genetics , Myocardial Ischemia/epidemiology , Hypertension/etiology , Inpatients , Cardiovascular System/physiopathology , Epidemiology, Descriptive , Cross-Sectional Studies , Abdominal Circumference , Observational Study , Heart Failure/etiology , Angina Pectoris/etiology , Life Style
8.
Rev. medica electron ; 41(4): 862-878, jul.-ago. 2019. tab
Article in Spanish | CUMED | ID: cum-76353

ABSTRACT

RESUMEN Introducción: las enfermedades cardiovasculares constituyen la principal causa de muerte en la mayoría de los países. Se describen los factores de riesgo para enfermedad coronaria como no modificables: edad, sexo y antecedentes familiares; y modificables relacionados al estilo de vida: tabaquismo, dislipidemia, obesidad, sedentarismo, diabetes, uso abusivo de alcohol y la enfermedad hipertensiva. Objetivo: caracterizar los factores de riesgo asociados a la cardiopatía isquémica en Atención Secundaria de Salud. Materiales y métodos: estudio observacional, descriptivo transversal en pacientes ingresados en el Hospital "Mártires del 9 de Abril" de Sagua la Grande, en el periodo comprendido entre los años 2016 y 2017. Integraron la muestra 96 pacientes que ingresaron con diagnóstico de cardiopatía isquémica. Se describieron las características demográficas de los mismos; fueron identificados los factores de riesgo y se determinó la frecuencia de asociación de otras formas clínicas de ateromatosis. Resultados: los pacientes fueron mayores de 60 años de edad; la mayoría tenían color de la piel blanca; presentaban antecedentes patológicos familiares de cardiopatía isquémica; las principales formas de cardiopatía isquémica fueron: angina e insuficiencia cardiaca; todos los pacientes presentaron uno o más factores de riesgo cardiovascular, los más significativos fueron, hipertensión arterial, tabaquismo aumento de la circunferencia abdominal y personalidad tipo "A". Conclusiones: la mayoría de los pacientes exhibieron alteraciones en el electrocardiograma: descenso del segmento ST, bloqueo de rama izquierda del haz de His y fibrilación auricular; se observó hipertrigliceridemia y se apreció asociación entre enfermedad renal crónica y angina (AU).


ABSTRACT Introduction: cardiovascular diseases are the main cause of death in most of the countries. The risk factors for coronary disease are described as unmodifiable: age, sex and family history; and modifiable related to lifestyle: smoking, dyslipidemia, obesity, sedentary lifestyle, diabetes, abusive use of alcohol and hypertensive disease. Objective: to characterize the risk factors associated to ischemic heart disease in secondary health care. Material and methods: observational, cross-sectional, descriptive study in patients admitted in "Mártires del 9 de Abril" Hospital, Sagua la Grande, between 2016 and 2017. The sample consisted of 96 patients admitted with a diagnosis of ischemic heart disease. Their demographic characteristics were described; the risk factors were identified and the frequency of association of other clinical forms of atheromatosis was determined. Results: the patients were aged more than 60 years; most of them were white people and had family pathological antecedents of ischemic heart disease; the main forms of ischemic heart disease were angina and heart failure; all patients showed one or more cardiovascular risk factors being arterial hypertension, smoking, increase of abdominal circumference and type A personality the most significant ones. Conclusions: the majority of patients showed alterations in the electrocardiogram: ST segment decrease, His bundle left branch blockage and atrial fibrillation; hypertriglyceridemia was observed and there was an association between chronic kidney disease and angina (AU).


Subject(s)
Humans , Aged , Tobacco Use Disorder/etiology , Risk Factors , Myocardial Ischemia/diagnosis , Myocardial Ischemia/genetics , Myocardial Ischemia/epidemiology , Hypertension/etiology , Inpatients , Cardiovascular System/physiopathology , Epidemiology, Descriptive , Cross-Sectional Studies , Abdominal Circumference , Observational Study , Heart Failure/etiology , Angina Pectoris/etiology , Life Style
9.
Bone Rep ; 10: 100203, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30989092

ABSTRACT

Our previous studies showed that in a mouse model in which PI3K-AKT activation was increased (YF mice), osteoclast numbers and levels of SDF-1, a chemokine, were augmented. The purpose of this study was to delineate the role of PI3K activation in regulating SDF-1 production and examine whether SDF-1 can stimulate differentiation and/or migration of osteoclast precursors. Using flow cytometric analysis, we demonstrated that compared to wild type mice, bone marrow of YF mice had increased numbers of CXCL12 abundant reticular (CAR) cells, that are a major cell type responsible for producing SDF-1. At the molecular level, transcription factor specificity protein 1 (Sp1) induced an increased transcription of SDF-1 that was dependent on PI3K/AKT activation. YF mice also contained an increased number of osteoclast precursors, in which expression of CXCR4, a major receptor for SDF-1, was increased. SDF-1 did not induce differentiation of osteoclast precursors into mature osteoclasts; compared to cells derived from WT mice, cells obtained from YF mice were more responsive to SDF-1. In conclusion, we demonstrate that PI3K activation resulted in increased SDF-1, increased the number of osteoclast precursors, and enhanced osteoclast precursor migration in response to SDF-1.

11.
J Environ Radioact ; 177: 290-304, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28800470

ABSTRACT

Hanabanilla and Paso Bonito Reservoirs are the main fresh water sources for about half a million inhabitants in central Cuba. Prior to this investigation precise information about the losses of storage capacity was not available. Sedimentation is the dominant process leading to reduction in water storage capacity. We investigated the sedimentation process in both reservoirs by analyzing environmental radionuclides (e.g. 210Pb, 226Ra and 137Cs) in sediment cores. In the shallow Paso Bonito Reservoir (mean depth of 6.5 m; water volume of 8 × 106 m3), we estimated a mean mass accumulation rate (MAR) of 0.4 ± 0.1 g cm-2y-1 based on 210Pb chronologies. 137Cs was detected in the sediments, but due to the recent construction of this reservoir (1975), it was not possible to use it to validate the 210Pb chronologies. The estimated MAR in this reservoir is higher than the typical values reported in similar shallow fresh water reservoirs worldwide. Our results highlight a significant loss of water storage capacity during the past 30 years. In the deeper and larger Hanabanilla Reservoir (mean depth of 15.5 m; water volume of 292 × 106 m3), the MAR was investigated in three different sites of the reservoir. The mean MARs based on the 210Pb chronologies varied between 0.15 and 0.24 g cm-2y-1. The MARs calculated based on the 137Cs profiles further validated these values. We show that the sediment accumulation did not change significantly over the last 50 years. A simple empirical mixing and sedimentation model that assumes 137Cs in the water originated from both, direct atmospheric fallout and the catchment area, was applied to interpret the 137Cs depth profiles. The model consistently reproduced the measured 137Cs profiles in the three cores (R2 > 0.9). Mean residence times for 137Cs in the water and in the catchment area of 1 y and 35-50 y, respectively were estimated. The model identified areas where the catchment component was higher, zones with higher erosion in the catchment, and sites where the fallout component was quantitatively recorded in the sediments.


Subject(s)
Cesium Radioisotopes/analysis , Lead Radioisotopes/analysis , Radiation Monitoring , Water Pollutants, Radioactive/analysis , Cuba , Geologic Sediments/chemistry
12.
Bone ; 103: 1-11, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28600151

ABSTRACT

Osteogenesis imperfecta (OI) is a disease caused by defects in type I collagen production that results in brittle bones. While the pathology is mainly caused by defects in the osteoblast lineage, there is also elevated bone resorption by osteoclasts resulting in high bone turnover in severe forms of the disease. Osteoclasts originate from hematopoietic myeloid cells, however changes in hematopoiesis have not been previously documented in OI. In this study, we evaluated hematopoietic lineage distribution and osteoclast progenitor cell frequency in bone marrow, spleen and peripheral blood of osteogenesis imperfecta murine (OIM) mice, a model of severe OI. We found splenomegaly in all ages examined, and expansion of myeloid lineage cells (CD11b+) in bone marrow and spleen of 7-9week old male OIM animals. OIM spleens also showed an increased frequency of purified osteoclast progenitors. This phenotype is suggestive of chronic inflammation. Isolated osteoclast precursors from both spleen and bone marrow formed osteoclasts more rapidly than wild-type controls. We found that serum TNFα levels were increased in OIM, as was IL1α in OIM females. We targeted inflammation therapeutically by treating growing animals with murine TNFR2:Fc, a compound that blocks TNFα activity. Anti-TNFα treatment marginally decreased spleen mass in OIM females, but failed to reduce bone resorption, or improve bone parameters or fracture rate in OIM animals. We have demonstrated that OIM mice have changes in their hematopoietic system, and form osteoclasts more rapidly even in the absence of OI osteoblast signals, however therapy targeting TNFα did not improve disease parameters.


Subject(s)
Myeloid Cells/pathology , Osteoclasts/pathology , Osteogenesis Imperfecta/pathology , Osteogenesis/physiology , Splenomegaly/etiology , Animals , Bone Marrow Cells/pathology , Female , Hematopoietic Stem Cells/pathology , Male , Mice
13.
Gac. méd. espirit ; 19(1): 80-86, ene.-abr. 2017.
Article in Spanish | LILACS | ID: biblio-840644

ABSTRACT

Fundamento: La intubación traqueal es el segundo procedimiento invasivo más utilizado en pacientes graves. Se han utilizado varios métodos para la comprobación de la intubación traqueal de forma satisfactoria, entre ellas la auscultación pulmonar, la capnografía, estudio radiológico y ecografía. Presentación de caso: Se presentó un caso que acudió al servicio de urgencias, por disnea intensa, se requirió atención en terapia intensiva y se realizó intubación rápida orotraqueal guiada por ecografía, método no utilizado habitualmente en Cuba y de que no se ha encontrado publicación alguna con anterioridad en revistas médicas cubanas. Se describió la técnica de intubación orotraqueal guiada por ecografía. Conclusiones: La intubación orotraqueal guiada por ecografía es un procedimiento seguro, fiable y repetible, además de verificar la correcta permanencia y posición adecuada del tubo endotraqueal.


Background: The tracheal intubation is the second invasive procedure used in critical patients. Several methods have been used for the confirmation of the tracheal intubation, among them the lung auscultation, capnography, radiological study and echography Presentation of the case: A case was assisted in the emergency room complaining of intense dyspnea, intensive care was needed and a rapid orotracheal intubation guided by ecography was performed, this method was not habitually carried out in Cuba where no records in publication were found previously in Cuban medical magazines. The technique of orotracheal intubation guided by ecography was carried out. Conclusions: The technique of orotracheal intubation guided by ecography is a safe, reliable and repeatable procedure, it also verifies the correct permanence and adequate position of orotracheal tube.


Subject(s)
Intubation, Intratracheal , Ultrasonography
14.
Gac méd espirit ; 19(1)ene.-abr. 2017. ilus
Article in Spanish | CUMED | ID: cum-69142

ABSTRACT

La intubación traqueal es el segundo procedimiento invasivo más utilizado en pacientes graves. Se han utilizado varios métodos para la comprobación de la intubación traqueal de forma satisfactoria, entre ellas la auscultación pulmonar, la capnografía, estudio radiológico y ecografía. Presentación de caso: Se presentó un caso que acudió al servicio de urgencias, por disnea intensa, se requirió atención en terapia intensiva y se realizó intubación rápida orotraqueal guiada por ecografía, método no utilizado habitualmente en Cuba y de que no se ha encontrado publicación alguna con anterioridad en revistas médicas cubanas. Se describió la técnica de intubación orotraqueal guiada por ecografía. Conclusiones: La intubación orotraqueal guiada por ecografía es un procedimiento seguro, fiable y repetible, además de verificar la correcta permanencia y posición adecuada del tubo endotraqueal(AU)


Subject(s)
Humans , Intubation, Intratracheal , Ultrasonography/methods
15.
Gac. méd. espirit ; 19(1): 80-86, ene.-abr. 2017.
Article in Spanish | CUMED | ID: cum-73680

ABSTRACT

Fundamento: La intubación traqueal es el segundo procedimiento invasivo más utilizado en pacientes graves. Se han utilizado varios métodos para la comprobación de la intubación traqueal de forma satisfactoria, entre ellas la auscultación pulmonar, la capnografía, estudio radiológico y ecografía. Presentación de caso: Se presentó un caso que acudió al servicio de urgencias, por disnea intensa, se requirió atención en terapia intensiva y se realizó intubación rápida orotraqueal guiada por ecografía, método no utilizado habitualmente en Cuba y de que no se ha encontrado publicación alguna con anterioridad en revistas médicas cubanas. Se describió la técnica de intubación orotraqueal guiada por ecografía. Conclusiones: La intubación orotraqueal guiada por ecografía es un procedimiento seguro, fiable y repetible, además de verificar la correcta permanencia y posición adecuada del tubo endotraqueal.


Background: The tracheal intubation is the second invasive procedure used in critical patients. Several methods have been used for the confirmation of the tracheal intubation, among them the lung auscultation, capnography, radiological study and echography Presentation of the case: A case was assisted in the emergency room complaining of intense dyspnea, intensive care was needed and a rapid orotracheal intubation guided by ecography was performed, this method was not habitually carried out in Cuba where no records in publication were found previously in Cuban medical magazines. The technique of orotracheal intubation guided by ecography was carried out. Conclusions: The technique of orotracheal intubation guided by ecography is a safe, reliable and repeatable procedure, it also verifies the correct permanence and adequate position of orotracheal tube.


Subject(s)
Humans , Intubation, Intratracheal , Ultrasonography
17.
J Biol Chem ; 291(8): 3882-94, 2016 Feb 19.
Article in English | MEDLINE | ID: mdl-26703472

ABSTRACT

Continuous parathyroid hormone (PTH) blocks its own osteogenic actions in marrow stromal cell cultures by inducing Cox2 and receptor activator of nuclear factor κB ligand (RANKL) in the osteoblastic lineage cells, which then cause the hematopoietic lineage cells to secrete an inhibitor of PTH-stimulated osteoblast differentiation. To identify this inhibitor, we used bone marrow macrophages (BMMs) and primary osteoblasts (POBs) from WT and Cox2 knock-out (KO) mice. Conditioned medium (CM) from RANKL-treated WT, but not KO, BMMs blocked PTH-stimulated cAMP production in POBs. Inhibition was reversed by pertussis toxin (PTX), which blocks Gαi/o activation. Saa3 was the most highly differentially expressed gene in a microarray comparison of RANKL-treated WT versus Cox2 KO BMMs, and RANKL induced Saa3 protein secretion only from WT BMMs. CM from RANKL-stimulated BMMs with Saa3 knockdown did not inhibit PTH-stimulated responses in POBs. SAA added to POBs inhibited PTH-stimulated cAMP responses, which was reversed by PTX. Selective agonists and antagonists of formyl peptide receptor 2 (Fpr2) suggested that Fpr2 mediated the inhibitory actions of Saa3 on osteoblasts. In BMMs committed to become osteoclasts by RANKL treatment, Saa3 expression peaked prior to appearance of multinucleated cells. Flow sorting of WT marrow revealed that Saa3 was secreted only from the RANKL-stimulated B220(-) CD3(-)CD11b(-/low) CD115(+) preosteoclast population. We conclude that Saa3 secretion from preosteoclasts, induced by RANKL in a Cox2-dependent manner, inhibits PTH-stimulated cAMP signaling and osteoblast differentiation via Gαi/o signaling. The induction of Saa3 by PTH may explain the suppression of bone formation when PTH is applied continuously and may be a new therapeutic target for osteoporosis.


Subject(s)
Cyclic AMP/metabolism , Osteoblasts/metabolism , Osteoclasts/metabolism , Parathyroid Hormone/pharmacology , Second Messenger Systems/drug effects , Serum Amyloid A Protein/metabolism , Animals , Antigens, CD/genetics , Antigens, CD/metabolism , Cell Differentiation/drug effects , Cell Differentiation/genetics , Cyclic AMP/genetics , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Gene Expression Regulation/drug effects , Gene Expression Regulation/genetics , Mice , Mice, Knockout , Osteoblasts/cytology , Osteoclasts/cytology , Osteogenesis/drug effects , Osteogenesis/genetics , Parathyroid Hormone/metabolism , RANK Ligand/genetics , RANK Ligand/metabolism , Receptors, Formyl Peptide/genetics , Receptors, Formyl Peptide/metabolism , Second Messenger Systems/genetics , Serum Amyloid A Protein/genetics
18.
Nucleus (La Habana) ; (57): 1-4, Jan.-June 2015.
Article in English | LILACS | ID: lil-754870

ABSTRACT

In this paper, we used the Monte Carlo simulations method in a well-type HPGe detector using directly the manufacturer supplied data in order to simulate the effi ciency response at 46.54 keV. The efficiency values were calculated as a function of the fi lling height of the sample into the measurement geometry and results were found in good agreement with experimental data. The main deviations were less than 2.5 % with a mean of 0.9 %, which is totally satisfactory for the purposes of environmental samples measurements. We also present a brief discussion about the response of the detector to different values of its geometric parameters.


En el trabajo se utilizaron los métodos de simulación por Monte Carlo en un detector HPGe tipo pozo, usando directamente los parámetros del fabricante para simular la respuesta en eficiencia a la energía de 46.54 keV. Los valores de efi ciencia se calcularon en función de la altura de la muestra en la geometría de medición y los resultados se correspondieron con los valores experimentales. Las mayores diferencias fueron menores que el 2.5 % con un promedio de 0.9 %, lo que es totalmente satisfactorio para la medición de muestras ambientales. Se presentó una breve discusión sobre la respuesta del detector para diferentes parámetros geométrico.

20.
Gac méd espirit ; 17(1)ene.-abr. 2015.
Article in Spanish | CUMED | ID: cum-60190

ABSTRACT

Los técnicos y profesionales publican los resultados de sus investigaciones para que sean leídas y analizadas por la comunidad interesada en dichos temas. La sesión Cartas al Editor propicia el debate de artículos publicados y favorece el intercambio de opiniones entre escritores, editores, revisores y lectores(AU)


Technicians and professionals publish their research results to be read and studied by the community interested in the topics. The section ‘Letters to the Editor favors the debate about the published articles and the exchange of opinions among writers, editors and readers(AU)


Subject(s)
Humans , Research Report , Anesthesia
SELECTION OF CITATIONS
SEARCH DETAIL
...