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1.
Nat Commun ; 13(1): 3504, 2022 Jun 17.
Article in English | MEDLINE | ID: mdl-35715391

ABSTRACT

Large Stokes shift fast emitters show a negligible reabsorption of their luminescence, a feature highly desirable for several applications such as fluorescence imaging, solar-light managing, and fabricating sensitive scintillating detectors for medical imaging and high-rate high-energy physics experiments. Here we obtain high efficiency luminescence with significant Stokes shift by exploiting fluorescent conjugated acene building blocks arranged in nanocrystals. Two ligands of equal molecular length and connectivity, yet complementary electronic properties, are co-assembled by zirconium oxy-hydroxy clusters, generating crystalline hetero-ligand metal-organic framework (MOF) nanocrystals. The diffusion of singlet excitons within the MOF and the matching of ligands absorption and emission properties enables an ultrafast activation of the low energy emission in the 100 ps time scale. The hybrid nanocrystals show a fluorescence quantum efficiency of ~60% and a Stokes shift as large as 750 meV (~6000 cm-1), which suppresses the emission reabsorption also in bulk devices. The fabricated prototypal nanocomposite fast scintillator shows benchmark performances which compete with those of some inorganic and organic commercial systems.

2.
Phys Chem Chem Phys ; 20(23): 15907-15915, 2018 Jun 13.
Article in English | MEDLINE | ID: mdl-29850733

ABSTRACT

In this work, we investigate the optical properties of hafnium dioxide nanocrystals, upon X-ray irradiation, looking for spectral evolution following thermal treatments in air up to 1000 °C that modify the crystal size as well as their point defect concentrations. Radio-luminescence measurements from 10 K up to room temperature reveal a rich and evolving picture of the optical features. A complete spectral analysis of the broad luminescence spectra reveals the presence of several emission components in the visible and UV regions. The lower energy components peaking at 2.1, 2.5, and 2.9 eV are characterized by a thermal quenching energy of 0.08 eV, while the corresponding value for the UV bands at 4.1 and 4.7 eV is close to 0.23 eV. We tentatively assign the components ranging from 2 to 3 eV to the presence of optically active defects of an intrinsic nature, together with the occurrence of titanium impurities; conversely, the bands at higher energies are likely to be of an excitonic nature. The comparison with previous photo-luminescence studies allows evidencing characteristic differences between the features of luminescence emissions caused by intra-centre excitation and those occurring under ionizing irradiation. Finally, scintillation measurements in the visible range reveal the existence of a fast decay in the nanosecond time scale for the smallest hafnia nanocrystals. This study offers a clear description of HfO2 luminescence characteristics upon excitation by X-rays and can lead to a better comprehension of the structure-property relationship at the nanoscale in metal oxides.

3.
Rev Gastroenterol Mex (Engl Ed) ; 83(4): 385-392, 2018.
Article in English, Spanish | MEDLINE | ID: mdl-29486973

ABSTRACT

INTRODUCTION AND AIMS: Graft-versus-host disease (GVHD) is a common multisystemic complication of allogeneic hematopoietic cell transplantation. The most frequent presentations of graft-versus-host disease involve the skin, the gastrointestinal tract, and the liver. The aim of the present study was to know the frequency of gastrointestinal tract and liver GVHD and the characteristics of disease presentation in pediatric patients that underwent hematopoietic stem cell transplantation (HSCT) at a tertiary care hospital center in Mexico City. MATERIAL AND METHODS: A retrospective study was carried out, utilizing the case records of patients that underwent HSCT in 2015, to determine the frequency of GVHD in pediatric patients at a Mexican tertiary care hospital center. RESULTS: In 2015, 16 HSCT were performed, 11 of which were carried out in males (68%). Only 3 patients developed graft-versus-host disease (18.7%). One patient presented with skin and liver GVHD and 2 patients presented with gastrointestinal tract and liver GVHD, which was the most frequent type. CONCLUSIONS: HSCT is still an uncommon procedure in Mexico and there is a lower frequency of gastrointestinal tract and liver GVHD than that reported in other studies. Most certainly, there will be an increase in this type of patient and risk factors in the Mexican population must still be determined to help predict the onset of GVHD.


Subject(s)
Gastrointestinal Diseases/epidemiology , Gastrointestinal Diseases/etiology , Graft vs Host Disease/epidemiology , Hematopoietic Stem Cell Transplantation/adverse effects , Liver Diseases/epidemiology , Liver Diseases/etiology , Adolescent , Child , Child, Preschool , Female , Gastrointestinal Diseases/pathology , Humans , Liver Diseases/pathology , Male , Mexico/epidemiology , Retrospective Studies , Skin Diseases/epidemiology , Skin Diseases/etiology , Tertiary Care Centers , Young Adult
4.
Копенгаген; Всемирная организация здравоохранения. Европейское региональное бюро; 2017. (WHO/EURO:2017-3012-42770-59677).
in Russian | WHO IRIS | ID: who-346205

ABSTRACT

Потребление сахаросодержащих напитков связано с повышенной калорийностью рациона, набором веса, избыточным весом и ожирением в большей степени, чем потребление любых других продуктов питания или напитков. Потребление сахаросодержащих напитков также приводит к развитию ряда неинфекционных заболеваний и болезней полости рта. Уже сейчас более половины населения Эстонии имеет избыточный вес или страдает ожирением, и этот показатель быстро растет, особенно среди детей и подростков. Важное место в данном аналитическом обзоре занимают дети, поскольку предпочтения в отношении напитков и их потребления формируются уже в раннем детстве и могут сохраняться впоследствии.


В обзоре представлены четыре направления политики, которые позволят снизить потребление сахаросодержащих напитков и их неблагоприятное воздействие на здоровье: регулирование рекламы продуктов питания; маркировка сахаросодержащих напитков и повышение осведомленности об их влиянии на здоровье; меры вмешательства и политики в области питания в школах; введение налогов на сахаросодержащие напитки, субсидирование других групп продуктов и/или замена сахаросодержащих напитков другими безалкогольными напитками.


Основываясь на сделанных нами выводах, мы пришли к заключению о том, что эти четыре направления политики дополняют друг друга, и осуществление их в комплексе поможет улучшить показатели здоровья населения. Комплексные и многокомпонентные вмешательства позволят снизить потребление сахаросодержащих напитков и их неблагоприятное воздействие на здоровье.


Subject(s)
Beverages , Dietary Sucrose , Food , Obesity , Estonia
5.
Copenhagen; World Health Organization. Regional Office for Europe; 2017. (WHO/EURO:2017-3012-42770-59676).
in English | WHO IRIS | ID: who-346203

ABSTRACT

The consumption of sugar-sweetened beverages is associated with increased energy intake, weight gain, overweight and obesity more than for any other food or beverage as well as with the development of several non-communicable diseases and poor oral health. Already, more than half of all Estonians are overweight or obese, and the numbers are rising rapidly, especially among children and adolescents. The brief focuses on children, as beverage preferences and consumption patterns develop early in childhood and can persist over time.


Four policy options were selected for reducing the consumption of sugar-sweetened beverages and their negative health effects: regulation of food advertising, labelling of sugar-sweetened beverages and raising awareness about their health effects, school interventions and nutrition policies, and imposing taxes on sugar-sweetened beverages, subsidizing other food groups and/or substituting alternative beverages.


Based on the findings it was concluded that the four policy options complement each other and, if implemented in combination, would help to reach the goal of better health outcomes. Comprehensive, multicomponent interventions will reduce the consumption of sugar-sweetened beverages and their negative health effects.


Subject(s)
Beverages , Dietary Sucrose , Food , Obesity , Estonia
6.
Rev Neurol ; 62(11): 493-501, 2016 Jun 01.
Article in Spanish | MEDLINE | ID: mdl-27222083

ABSTRACT

INTRODUCTION: Intellectual disability refers to substantial limitations in intellectual functioning, affecting 0.7-1.5% of the population. People with intellectual disability have higher rates of obesity, since caloric values and nutritional status, are deficient. AIMS: To determine the nutritional habits, analyze the effectiveness of nutritional education and evaluate the possible effect of improvement introducing exercise and nutrition workshops, in a group of people with intellectual disability. PATIENTS AND METHODS: Clinical, nutritional and anthropometric (weight, height, body mass index, body fat, waist circumference) assessment was conducted in 47 patients. An ad hoc survey was designed in which exercise habits, medical and dietary history, record of 72 hours (including 2 weekdays and 1 weekend) and the adherence to Mediterranean diet data were collected. The workshops of exercise and nutrition counted with a structure of theoretical-practical explanation and games. RESULTS: 76.1% presented weight excess at baseline. After the intervention values of total body fat (-0.94 ± 4.4%) and visceral fat (-0.86 ± 2%), weight (-0.4 ± 3.3 kg) and body mass index (-0.2 ± 1.6 kg/m2) decreased, more in women than in men. 60.5% of subjects did not meet a high adherence to the Mediterranean diet. After nutritional intervention, a significant difference (p <= 0,001) was observed in the KidMed score. The workshop of physical activity had positive effects on the anthropometry of subjects. CONCLUSIONS: Both the intake and the prevalence of obesity in this group of people are inadequate. Nutritional education and physical exercise workshops are useful for working with this group, achieving significant changes to prevent obesity and improve their health.


TITLE: Analisis del estado nutricional y composicion corporal de personas con discapacidad intelectual.Introduccion. La discapacidad intelectual, definida como limitaciones sustanciales en el funcionamiento intelectual, afecta al 0,7-1,5% de la poblacion. Estas personas presentan mayores tasas de obesidad, y sus valores caloricos y estado nutricional son deficientes. Objetivos. Conocer los habitos nutricionales, analizar la eficacia de la educacion nutricional y evaluar la posible mejora, introduciendo talleres de ejercicio fisico y nutricion, en la discapacidad intelectual. Pacientes y metodos. Se realizo una valoracion clinica, nutricional y antropometrica (peso, talla, indice de masa corporal, grasa corporal, perimetro de la cintura) a 47 sujetos con discapacidad intelectual. Se registraron los habitos deportivos, la historia clinica y la historia dietetica mediante un registro alimentario y un cuestionario de adhesion a la dieta mediterranea (KidMed). Los talleres de nutricion y ejercicio fisico contaron con una estructura de explicacion teorica, practica y juegos. Resultados. El 76,1% presentaba exceso ponderal en el inicio del estudio. Tras la intervencion, los valores de grasa corporal (­0,94 ± 4,4%) y grasa visceral (­0,86 ± 2%), asi como el peso (­0,4 ± 3,3 kg) y el indice de masa corporal (­0,2 ± 1,6 kg/m2), disminuyeron, mas en las mujeres que en los hombres. El 60,5% no cumplia con una alta adhesion a la dieta mediterranea. Tras la intervencion, se observo una diferencia significativa (p <= 0,001) en la puntuacion del KidMed. El taller de actividad fisica tuvo efectos positivos sobre la antropometria. Conclusiones. La alimentacion fue inadecuada en la mayoria de los individuos. La prevalencia de obesidad fue elevada. Los talleres de educacion nutricional y de ejercicio son una herramienta util para trabajar con este colectivo, y consiguen cambios significativos para prevenir la obesidad y mejorar su salud.


Subject(s)
Body Composition , Intellectual Disability/physiopathology , Nutritional Status , Anthropometry , Body Mass Index , Female , Humans , Male , Obesity/epidemiology
7.
Kopenhaagen; Maailma Terviseorganisatsiooni. Euroopa Regionaalbüroo; 2016. (WHO/EURO:2016-3012-42770-59675).
in Estonian | WHO IRIS | ID: who-346204

ABSTRACT

Suhkruga magustatud jookide tarbimine on kehakaalu tõusuga tugevamini seotud kui ühegi muu toidu või joogi tarbimine, samuti on nende tarbimine seotud mitmetesse mittenakkushaigustesse haigestumisega ja halvenenud suuõõnetervisega. Juba praegu on üle poole Eesti elanikest ülekaalulised või rasvunud ja nende osatähtsus rahvastikus kasvab kiiresti, eriti laste ja noorukite seas. Tõenduspõhisuse ülevaade keskendub eelkõige just lastele ja noortele, sest joogieelistused ja tarbimismustrid kujunevad välja juba varases lapsepõlves ja need võivad püsida pikka aega.


Suhkruga magustatud jookide tarbimise ja nende negatiivse tervisemõju vähendamiseks käsitleti nelja poliitikavalikut: toiduturunduse meetmed, suhkruga magustatud jookide märgistus ja teadlikkuse tõstmine nende tervisemõjust, sekkumismeetmed koolides ja koolide toidupoliitika ning suhkruga magustatud jookide maksustamine, muude toidugruppide subsideerimine ja/või alternatiivsete jookidega asendamine.


Tulemuste põhjal järeldati, et neli poliitikavalikut on üksteist täiendavad ja nende kombineerimine aitab saavutada parema tervisetulemi eesmärki. Laiahaardelised, mitme komponendiga sekkumismeetmed vähendavad suhkruga magustatud jookide tarbimist ja nende negatiivset tervisemõju.


Subject(s)
Beverages , Dietary Sucrose , Food , Obesity , Estonia
8.
Leg Med (Tokyo) ; 17(1): 60-4, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25258096

ABSTRACT

Peripheral quantitative computed tomography (pQCT) has found new fields of application in bone medicine, but none of them concerns the forensic practice. This study exposes the potential of pQCT applied to a penetrating lesion in a vertebral body. A pQCT scanner was used for the measurements (XCT Research SA+; Stratec Medizintechnik GmbH, Pforzheim, Germany). A more precise reconstruction of the path of the lesion within the trabecular bone was reached, with more details concerning the morphological characteristics of the lesion inside the vertebral body, and the elaboration of a 3D model was created, which allowed the operator to define the volume of the lack of tissues related to the lesion. The application of pQCT scan proved to be a potentially useful tool for the assessment of bone lesions, although further studies are needed in order to verify its applicability to forensic context.


Subject(s)
Forensic Pathology/methods , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/injuries , Tomography, X-Ray Computed/methods , Wounds, Stab/diagnosis , Autopsy , Female , Humans , Skeleton
10.
Osteoporos Int ; 23(7): 1967-75, 2012 Jul.
Article in English | MEDLINE | ID: mdl-21947103

ABSTRACT

SUMMARY: Osteoarthritis is linked to a reduced risk of femoral fracture despite osteoporosis. Different bone distribution in the femoral neck in osteoarthritis and fracture was revealed using a peripheral quantitative computed tomography (pQCT) comparative analysis. Our findings sustain the presence of an adaptive mechanism of bone structure providing fracture protection in osteoarthritis. INTRODUCTION: Although osteoarthritis is associated with reduced femoral fracture risk, it does not protect from bone loss. We investigated whether adaptive mechanisms are present at the arthritic joint, leading to reduced fracture risk, despite the presence of low bone mass density. METHODS: We performed pQCT comparative analyses of human femoral neck specimens derived from 32 postmenopausal women who received hip prostheses for osteoarthritis (n = 19) or femoral fracture (n = 13) by applying an in-house automated software to extract bone structure descriptors, characterize trabecular and cortical bone distribution, and evaluate their mutual relationships. RESULTS: The cortical bone volume and trabecular thickness were significantly (p < 0.05) higher in the osteoarthritis group than in the fracture group. Trabecular bone volume was also significantly (p < 0.05) higher in the osteoarthritis group than the fracture group at the inferior and anterior quadrants. Significance was maintained after adjusting for age, cortical bone volume, and cortical porosity thickness. Multiple linear regression analysis showed that thickness, volume, and apparent density of the trabecular region significantly (p < 0.05) correlated with the same cortical descriptors in osteoarthritis, but no significant relationship was found in the fracture group. Age differentially affected the mutual relationships in the two groups, showing a significant correlation with trabecular thickness in both groups and with apparent trabecular density only in femoral fracture group. CONCLUSIONS: Starting from these differences in the structural descriptors, our study sustains the presence of a compensatory mechanism in osteoarthritis to preserve the mechanical competence of bone structure, despite the loss of trabecular bone, underlying lower fracture risk.


Subject(s)
Bone Density/physiology , Femoral Neck Fractures/physiopathology , Femur Neck/physiopathology , Osteoarthritis, Hip/physiopathology , Osteoporosis, Postmenopausal/physiopathology , Age Factors , Aged , Aged, 80 and over , Arthroplasty, Replacement , Female , Femoral Neck Fractures/complications , Femoral Neck Fractures/diagnostic imaging , Femoral Neck Fractures/surgery , Femur Neck/diagnostic imaging , Humans , Image Processing, Computer-Assisted/methods , Osteoarthritis, Hip/complications , Osteoarthritis, Hip/diagnostic imaging , Osteoarthritis, Hip/surgery , Osteoporosis, Postmenopausal/complications , Osteoporosis, Postmenopausal/diagnostic imaging , Osteoporotic Fractures/complications , Osteoporotic Fractures/diagnostic imaging , Osteoporotic Fractures/physiopathology , Osteoporotic Fractures/surgery , Tomography, X-Ray Computed , Weight-Bearing/physiology
11.
Ann Biomed Eng ; 39(1): 172-84, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20824341

ABSTRACT

We developed an automatic method for regional analysis of femoral neck images acquired by peripheral quantitative computed tomography (pQCT), based on automatic spatial re-alignment and segmentation; the segmentation method, based on a morphological approach, explicitly accounts for the presence of three different bone compartments: cortical region, trabecular region, and transition zone between cortical and trabecular compartments. The proposed method was applied on 13 femoral neck sections derived from female donors who were undergoing hip replacement surgery for primary degenerative arthritis or fracture, and a typical densitometric and structural analysis was performed both globally and regionally. The proposed segmentation method was quantitatively evaluated by comparing automatic contour and the corresponding manual contours delineated by three operators using metrics based on surface distance (average symmetric distance, ASD) and volumetric overlapping (dice similarity coefficient, DSC). The same approach was used to validate the automatic spatial orientation, considering as metric the difference between manual and automatic angle orientation. Results confirm a satisfactory agreement between automatic and manual performances (ASD < 0.41 mm, DSC > 0.91, orientation difference = 3.61°) and show that globally our algorithm performs very well. Concerning regional analysis application, from our results we can observe that significant differences are present among the four bone quadrants.


Subject(s)
Algorithms , Artificial Intelligence , Femur Neck/diagnostic imaging , Pattern Recognition, Automated/methods , Radiographic Image Interpretation, Computer-Assisted/methods , Aged , Aged, 80 and over , Female , Humans , Radiographic Image Enhancement/methods , Reproducibility of Results , Sensitivity and Specificity
12.
J Phys Chem A ; 114(30): 7912-7, 2010 Aug 05.
Article in English | MEDLINE | ID: mdl-20666539

ABSTRACT

The diffusion-controlled electron transfer rate constants (k(d)) of several quenching reactions of ruthenium complexes [Ru(L)(3)](2+*) (L = bpy, phen, and 4,7-(CH(3))(2)phen) with [Fe(CN)(6)](3-) were experimentally determined at different concentrations of NaNO(3). From these rate constants, the effective values of viscosity coefficients for NaNO(3) solutions were calculated using EMSA (exponential mean spherical approximation) and EF (Eigen-Fuoss) approaches in order to take into account the mean force potential between reactants. The reliability of the effective parameters were checked through calculations of the rate constants of the reaction [IrCl(6)](2-)+ [Ru(bpy)(3)](2+)* in these NaNO(3) solutions. The rate constants of this reaction were also obtained by fluorescence quenching measurements. The agreement between the two sets of data (experimental and predicted) is excellent. The trends of association (k(d)) and dissociation (k(-d)) rate constants for 2+/3-, 2+/2-, and 2+/2+ reactions in NaNO(3) solutions are discussed. The use of effective diffusion coefficients for estimating k(d) and k(-d) allowed us to obtain the intrinsic electron transfer rate constant (k(et)) for the activation-diffusion-controlled process between [Ru(bpy)(3)](2+)* and [Co(NH(3))(5)Cl](2+) complexes from the observed (quenching) rate constant. The trend of electron-transfer rate constant in NaNO(3) for this reaction was rationalized by using the Marcus electron-transfer treatment.

13.
Philos Trans A Math Phys Eng Sci ; 368(1921): 2841-51, 2010 Jun 28.
Article in English | MEDLINE | ID: mdl-20478909

ABSTRACT

The virtual physiological human (VPH) initiative encompasses a wide range of activities, including structural and functional imaging, data mining, knowledge discovery tool and database development, biomedical modelling, simulation and visualization. The VPH community is developing from a multitude of relatively focused, but disparate, research endeavours into an integrated effort to bring together, develop and translate emerging technologies for application, from academia to industry and medicine. This process initially builds on the evolution of multi-disciplinary interactions and abilities, but addressing the challenges associated with the implementation of the VPH will require, in the very near future, a translation of quantitative changes into a new quality of highly trained multi-disciplinary personnel. Current strategies for undergraduate and on-the-job training may soon prove insufficient for this. The European Commission seventh framework VPH network of excellence is exploring this emerging need, and is developing a framework of novel training initiatives to address the predicted shortfall in suitably skilled VPH-aware professionals. This paper reports first steps in the implementation of a coherent VPH training portfolio.


Subject(s)
Computer Simulation , Models, Biological , Physiology/education , User-Computer Interface , Europe , Humans , Interdisciplinary Communication
14.
Br J Pharmacol ; 154(6): 1225-35, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18500359

ABSTRACT

BACKGROUND AND PURPOSE: The present study was designed to assess whether cyclooxygenase-2 (COX-2) activation is involved in the effects of chronic aldosterone treatment on endothelial function of mesenteric resistance arteries (MRA) from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). EXPERIMENTAL APPROACH: Relaxation to acetylcholine was measured in MRA from both untreated and aldosterone-treated strains. Vasomotor responses to prostacyclin and U46619 were also analysed. Release of 6-oxo-prostaglandin (PG)F1alpha and thromboxane B2 (TxB2) was determined by enzyme immunoassay. COX-2 protein expression was measured by western blot. KEY RESULTS: Aldosterone reduced acetylcholine relaxation in MRA from both strains. In MRA from both aldosterone-treated strains the COX-1/2 or COX-2 inhibitor (indomethacin and NS-398, respectively), TxA2 synthesis inhibitor (furegrelate), prostacyclin synthesis inhibitor (tranylcypromine) or TxA2/ PGH2 receptor antagonist (SQ 29 548), but not COX-1 inhibitor SC-560, increased acetylcholine relaxation. In untreated rats this response was increased only in SHR. Prostacyclin elicited a biphasic vasomotor response: lower concentrations elicited relaxation, whereas higher concentrations elicited contraction that was reduced by SQ 29 548. Aldosterone increased the acetylcholine-stimulated production of 6-oxo-PGF(1alpha) and TxB2 in MRA from both strains. COX-2 expression was higher in both strains of rats treated with aldosterone. CONCLUSIONS AND IMPLICATIONS: Chronic treatment with aldosterone impaired endothelial function in MRA under normotensive and hypertensive conditions by increasing COX-2-derived prostacyclin and thromboxane A2. As endothelial dysfunction participates in the pathogenesis of many cardiovascular disorders we hypothesize that anti-inflammatory drugs, specifically COX-2 inhibitors, could ameliorate vascular damage in patients with elevated aldosterone production.


Subject(s)
Aldosterone/pharmacology , Endothelium, Vascular/drug effects , Epoprostenol/metabolism , Thromboxane A2/metabolism , Vascular Diseases/chemically induced , 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology , Animals , Blotting, Western , Cyclooxygenase 1/metabolism , Cyclooxygenase 2/metabolism , In Vitro Techniques , Male , Mesenteric Arteries/pathology , Muscle Relaxation/drug effects , Muscle, Smooth, Vascular/drug effects , Norepinephrine/pharmacology , Potassium Chloride/pharmacology , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Vascular Diseases/pathology , Vascular Resistance/drug effects , Vasoconstrictor Agents/pharmacology
15.
Cytotherapy ; 9(6): 600-10, 2007.
Article in English | MEDLINE | ID: mdl-17882725

ABSTRACT

BACKGROUND: GvHD is a serious and potentially life-threatening side-effect of allogeneic BMT, caused by alloreactive cells attacking normal host cells. A number of different approaches have been attempted to remove allo-activated cells from the graft prior to transplantation. When developing such assays, there is a need to control for unwanted removal of cells, as well as depletion efficiency related to activation kinetics. METHODS: The specific activation induced by the superantigens SEB and TSST-1 of T cells with defined Vbeta chains was utilized to follow activation of bystander cells and the kinetics of specific cellular activation by flow cytometry. RESULTS: The activation marker CD69 was up-regulated on bystander T cells, and was only transiently highly expressed on the specific T cells, making this marker unreliable for removal of alloreactive cells. In contrast, CD25 was found only on specifically activated T cells and was stably expressed over several days. However, it was not detected on all specific cells until day 6. Likewise, proliferation occurred only in T cells expressing the expected Vbeta chains, with all activated cells having undergone at least one cell cycle by day 4. DISCUSSION: In conclusion, our assay demonstrates that only temporary bystander activation occurs when polyclonally activating T cells by SEB or TSST-1, and that CD25, but not CD69, can be used for removal of specifically activated cells. Furthermore, this assay is useful for monitoring methods aiming at specific removal of cycling cells.


Subject(s)
Biological Assay/methods , Stem Cell Transplantation , Antigens, CD , Antigens, Differentiation, T-Lymphocyte , Biomarkers , Cell Proliferation , Cell Separation , Humans , Interleukin-2 Receptor alpha Subunit , Kinetics , Lectins, C-Type , Lymphocyte Activation , T-Lymphocytes/cytology , Transplantation, Homologous
17.
J Endocrinol ; 192(3): 639-45, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17332531

ABSTRACT

It is presently thought that osteoprotegerin (OPG) is a cytokine involved in the regulation of osteoblast/osteoclast crosstalk and maintenance of bone mass. Recent studies showed that GH replacement therapy in GH-deficient patients was able to induce a significant increase of OPG in the plasma, as well as in the cortical and the trabecular bone. In order to determine whether GH could directly modulate OPG secretion, the effect of GH on human osteoblast-like cells (hOB) in primary culture was studied. After detecting the presence of the mRNA for the GH receptor (GHR) by RT-PCR, hOB were exposed to increasing concentrations of GH, from 0.1 to 25 ng/ml, for 24 h. The results showed that GH exposure was able to stimulate OPG secretion in a concentration-dependent manner. In addition, the OPG mRNA levels were increased, indicating that the hormone has a stimulatory effect on gene expression. The stimulatory effect on OPG expression and production was prevented by exposing the cells to tyrphostin AG490 (10 muM), an inhibitor of Janus kinase 2, which is one of the kinases involved in the intracellular pathway activated by the binding of GH to its receptor. Similar results were obtained when the cells were exposed to a receptor antagonist of GH, pegvisomant at 50 nM. GH exposure neither induced an increase in IGF-I expression nor secretion in hOB. These results suggest that the stimulation of OPG production induced by GH in hOB is specific and receptor mediated and further support the view that GH is able to modulate bone remodeling by directly influencing osteoblast-osteoclast crosstalk.


Subject(s)
Growth Hormone/pharmacology , Osteoblasts/metabolism , Osteoprotegerin/metabolism , Analysis of Variance , Cells, Cultured , Human Growth Hormone/analogs & derivatives , Human Growth Hormone/pharmacology , Humans , Osteoblasts/drug effects , Osteoprotegerin/genetics , Protein-Tyrosine Kinases/antagonists & inhibitors , RNA, Messenger/analysis , Receptors, Somatotropin/antagonists & inhibitors , Reverse Transcriptase Polymerase Chain Reaction , Tyrphostins/pharmacology
19.
20.
Am J Physiol Cell Physiol ; 291(3): C529-37, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16611736

ABSTRACT

The osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB ligand (RANKL)/receptor activator of nuclear factor-kappaB (RANK) system was evaluated as a potential target of CGRP anabolic activity on bone. Primary cultures of human osteoblast-like cells (hOB) express calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1, and, because CGRP stimulates cAMP (one of the modulators of OPG production in osteoblasts), it was investigated whether it affects OPG secretion and expression in hOB. CGRP treatment of hOB (10(-11) M-10(-7) M) dose-dependently inhibited OPG secretion with an EC(50) of 1.08 x 10(-10) M, and also decreased its expression. This action was blocked by the antagonist CGRP(8-37). Forskolin, a stimulator of cAMP production, and dibutyryl cAMP also reduced the production of OPG. CGRP (10(-8) M) enhanced protein kinase A (PKA) activity in hOB, and hOB exposure to the PKA inhibitor, H89 (2 x 10(-6) M), abolished the inhibitory effect of CGRP on OPG secretion. Conditioned media from CGRP-treated hOB increased the number of multinucleated tartrate-resistant acid phosphatase-positive cells and the secretion of cathepsin K in human peripheral blood mononuclear cells compared with the conditioned media of untreated hOB. These results show that the cAMP/PKA pathway is involved in the CGRP inhibition of OPG mRNA and protein secretion in hOB and that this effect favors osteoclastogenesis. CGRP could thus modulate the balance between osteoblast and osteoclast activity, participating in the fine tuning of all of the bone remodeling phases necessary for the subsequent anabolic effect.


Subject(s)
Calcitonin Gene-Related Peptide/physiology , Cyclic AMP-Dependent Protein Kinases/metabolism , Cyclic AMP/metabolism , Glycoproteins/metabolism , Osteoblasts/physiology , Receptors, Cytoplasmic and Nuclear/metabolism , Receptors, Tumor Necrosis Factor/metabolism , Acid Phosphatase/analysis , Aged , Bone Remodeling/physiology , Calcitonin Gene-Related Peptide/pharmacology , Calcitonin Gene-Related Peptide Receptor Antagonists , Carrier Proteins/genetics , Carrier Proteins/metabolism , Cathepsin K , Cathepsins/pharmacology , Cell Separation , Colforsin/pharmacology , Femoral Fractures/pathology , Humans , Isoenzymes/analysis , Leukocytes, Mononuclear/drug effects , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Middle Aged , Osteoblasts/drug effects , Osteoclasts/drug effects , Osteoclasts/physiology , Osteoprotegerin , Peptide Fragments/pharmacology , RANK Ligand , Receptor Activator of Nuclear Factor-kappa B , Receptors, Calcitonin Gene-Related Peptide/metabolism , Signal Transduction , Tartrate-Resistant Acid Phosphatase
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