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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.
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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.
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Densidade Óssea/fisiologia , Fraturas do Colo Femoral/fisiopatologia , Colo do Fêmur/fisiopatologia , Osteoartrite do Quadril/fisiopatologia , Osteoporose Pós-Menopausa/fisiopatologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Substituição , Feminino , Fraturas do Colo Femoral/complicações , Fraturas do Colo Femoral/diagnóstico por imagem , Fraturas do Colo Femoral/cirurgia , Colo do Fêmur/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador/métodos , Osteoartrite do Quadril/complicações , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/cirurgia , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/diagnóstico por imagem , Fraturas por Osteoporose/complicações , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/fisiopatologia , Fraturas por Osteoporose/cirurgia , Tomografia Computadorizada por Raios X , Suporte de Carga/fisiologiaRESUMO
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.
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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.
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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.
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Aldosterona/farmacologia , Endotélio Vascular/efeitos dos fármacos , Epoprostenol/metabolismo , Tromboxano A2/metabolismo , Doenças Vasculares/induzido quimicamente , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Animais , Western Blotting , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Técnicas In Vitro , Masculino , Artérias Mesentéricas/patologia , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Norepinefrina/farmacologia , Cloreto de Potássio/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Doenças Vasculares/patologia , Resistência Vascular/efeitos dos fármacos , Vasoconstritores/farmacologiaRESUMO
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.
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Gastroenteropatias/epidemiologia , Gastroenteropatias/etiologia , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatias/epidemiologia , Hepatopatias/etiologia , Adolescente , Criança , Pré-Escolar , Feminino , Gastroenteropatias/patologia , Humanos , Hepatopatias/patologia , Masculino , México/epidemiologia , Estudos Retrospectivos , Dermatopatias/epidemiologia , Dermatopatias/etiologia , Centros de Atenção Terciária , Adulto JovemRESUMO
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.
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Hormônio do Crescimento/farmacologia , Osteoblastos/metabolismo , Osteoprotegerina/metabolismo , Análise de Variância , Células Cultivadas , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/farmacologia , Humanos , Osteoblastos/efeitos dos fármacos , Osteoprotegerina/genética , Proteínas Tirosina Quinases/antagonistas & inibidores , RNA Mensageiro/análise , Receptores da Somatotropina/antagonistas & inibidores , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tirfostinas/farmacologiaAssuntos
Arterite de Células Gigantes/genética , Polimorfismo de Nucleotídeo Único , Polimialgia Reumática/genética , Receptor Toll-Like 9/genética , Idoso , Idoso de 80 Anos ou mais , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
This study was designed to evaluate whether or not continuous intracerebroventricular infusion of leptin (1.5 microg/rat/24 h, for 28 days) produced different regional response on the skeleton of growing rats. Leptin reduce the accretion of total femoral bone mineral content (BMC) and density (BMD). This effect was related to a reduction of metaphyseal femur as no changes were detected in the diaphysis. Despite the reduced accretion in the volumetric of both femur and tibia compared to controls, leptin had no significant effects on the lumbar vertebrae. Urine deoxypyrydinoline and serum osteocalcin remained more elevated in the leptin-treated group as compared to controls. The results demonstrate that long-term central infusion of leptin activates bone remodeling with a negative balance. Leptin induces distinct responses in the different structure of bone and in the axial and appendicular skeleton.
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Densidade Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Encéfalo/metabolismo , Leptina/administração & dosagem , Animais , Peso Corporal , Osso e Ossos/metabolismo , Leptina/metabolismo , Masculino , Osteocalcina/sangue , Peptídeos/química , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
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.
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Composição Corporal , Deficiência Intelectual/fisiopatologia , Estado Nutricional , Antropometria , Índice de Massa Corporal , Feminino , Humanos , Masculino , Obesidade/epidemiologiaRESUMO
Significant changes in body composition, body fat distribution, and resting metabolic rate (RMR) occur with aging. Interestingly, studies on human longevity pointed out that long-lived subjects are less prone to the anthropometrics and metabolic derangement normally observed in the elderly. Indeed, the relationship between energy expenditure and longevity has been poorly investigated. Thus, energy expenditure parameters of 28 long-lived subjects were assessed and compared with those of 26 adults and 27 younger elderly. All subjects enrolled were female. In the whole population, RMR was negatively correlated with age (P < 0.05), waist to hip ratio (WHR) (P < 0.001), fat mass (P < 0.001), and percent body fat (P < 0.03); respiratory quotient (Rq) displayed an age-related decrease (P < 0.001) and was negatively correlated with WHR (P < 0.001) and fat-free mass (FFM) (P < 0.006). In multivariate analysis, both RMR and Rq had FFM, WHR, but not body mass index as significant and independent determinants. Splitting the whole study group into subgroups according to age, long-lived subjects had oxygen volume, carbon dioxide volume, and Rq significantly higher than aged subjects but lower than adult subjects. In addition, long-lived subjects had total volume of expired air and RMR greater than aged subjects but not different from ones found in adults. In long-lived subjects, Rq was negatively correlated with percent body fat (P < 0.02), plasma glucose (P < 0.05), free fatty acid (P < 0.05), and WHR (P < 0.05), whereas RMR was negatively correlated with WHR (P < 0.05). No significant associations of RMR and Rq with FFM were found. In conclusion, our data demonstrate that human longevity seems protected toward an age-related decline. It is likely that the lack of the anthropometrics derangement may preserve long-lived subjects from the age-related decrease in energy metabolism.
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Metabolismo Basal , Longevidade , Respiração , Adulto , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Metabolismo Energético , Feminino , Humanos , Pessoa de Meia-Idade , Relação Cintura-QuadrilRESUMO
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.
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Patologia Legal/métodos , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/lesões , Tomografia Computadorizada por Raios X/métodos , Ferimentos Perfurantes/diagnóstico , Autopsia , Feminino , Humanos , EsqueletoRESUMO
This study was undertaken to assess the sensitivity of hydroxylysylpyridinoline (HP), lysylpyridinoline (LP), galactosylhydroxylysine (GHyl) and glucosylgalactosylhydroxylysine (GGHyl) to monitor bone response to estrogen deficiency and replacement by comparing their excretory patterns in ovariectomized aged (11-14 months old) rats. The ovariectomized (OVX) rats were randomized into two groups: (1) OVX plus vehicle; (2) OVX plus 17 beta-estradiol (17-beta E, 10 micrograms/kg, s.c., 4 days/week). Treatment with 17-beta E started immediately after OVX and continued for 60 days. The collagen catabolites were measured in urine for 1 month before OVX and thereafter for 60 days. In temporal coincidence with urine collection, bone area and bone mineral density (BMD) of lumbar vertebrae, femoral diaphysis and distal metaphysis were measured by dual-energy X-ray absorptiometry. In the untreated rats, BMD of the femoral metaphysis and lumbar vertebrae decreased significantly and the urinary excretion of LP, HP, GHyl and GGHyl increased with different patterns. In the treated rats, 17-beta E replacement prevented the increment in LP excretion, partially prevented the increase in HP excretion, but had no effect on the excretion of GHyl and GGHyl. In conclusion pyridinolines and glycosides have different sensitivities to the bone response to OVX. Glycoside excretion after OVX also reflects metabolic processes not strictly related to bone loss and, in contrast with LP, is not sensitive to estrogen replacement.
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Estradiol/uso terapêutico , Terapia de Reposição de Estrogênios , Hidroxilisina/análogos & derivados , Ovariectomia , Compostos de Piridínio/urina , Absorciometria de Fóton , Aminoácidos/urina , Animais , Biomarcadores/urina , Osso e Ossos/metabolismo , Feminino , Hidroxilisina/urina , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: The aim of this study was to assess the responsiveness of two classes of bone resorption markers to the enhancement of osteoclastic activity induced by orchiectomy and to its inhibition by clodronate treatment in mature rats. DESIGN: Bone mineral density (BMD) at femural metaphysis, femural diaphysis, lumbar vertebrae, and the urinary excretion of pyridinoline (Pyr), deoxypyridinoline (D-Pyr), galactosylhydroxylysine (GHyl) and glucosylgalactosylhydroxylysine (GGHyl) were monitored at regular intervals for 30 days prior to and for 60 days following orchiectomy in eleven rats, divided into two groups: five rats untreated and the other six treated with clodronate. RESULTS: Prior to orchiectomy, a significant (P < 0.01) decrease in BMD was observed only at the distal femural metaphysis. This decrease appeared to be associated with a time-dependent increase in the urinary excretion of all markers. Following orchiectomy, the BMD of the untreated group decreased significantly (P < 0.01) at all bone sites. The bone loss was accompanied by a significant (P < 0.01) increase in Pyr and D-Pyr concentrations in urine, whereas urinary GHyl and GGHyl did not change significantly. In the clodronate-treated group, the BMD of the three skeletal sites did not change significantly, while the urinary excretion of all urinary biochemical markers decreased significantly (P < 0.001). CONCLUSION: This study showed that pyridinolines are able to monitor the bone response to orchiectomy and to clodronate treatment response in androgen-deficient mature male rat. whereas glycosides appear prone to confounding factors.
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Envelhecimento/urina , Reabsorção Óssea/urina , Ácido Clodrônico/farmacologia , Orquiectomia , Animais , Biomarcadores/urina , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/metabolismo , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: The present study was performed to evaluate the potential influence of the estrogen milieu in modulating the effects of GH/IGF stimulation by a GH-releasing peptide, hexarelin (HEXA), on bone metabolism and mineral density in middle-aged female rats. METHODS: HEXA was administered for 60 days (50 microg/kg s.c. twice a day) to intact and ovariectomized (OVX) 11-month-old female rats and changes in bone parameters were evaluated with respect to those of the same rats under baseline conditions and with those of control rats (intact and OVX) administered isovolumetric amounts of physiological saline. Serum total alkaline phosphatase (ALP) and urinary deoxypyridinoline (Dpd) were measured before and at various times during HEXA treatment. Bone mineral content (BMC) and density of lumbar vertebrae and femoral mid-diaphyses were measured by dual energy X-ray absorptiometry before and after treatment. In all groups, serum IGF-I levels were determined before and during treatment and the GH secretory response to HEXA was assessed at the end of the experiment. RESULTS: In intact rats, HEXA did not modify Dpd urinary excretion, induced a trend toward an increase of serum ALP activity and significantly increased BMC (+6.5%) and bone area (+4.1%) only at lumbar vertebrae. In OVX rats, HEXA did not modify the OVX-induced increase in bone turnover markers (Dpd and ALP) and did not affect the OVX-induced vertebral bone loss, but significantly increased BMC (+7.2%) and bone area (+5.3%) at femoral mid-diaphyses. HEXA significantly increased serum IGF-I levels at day 14, but not at day 60, in both intact and OVX rats, whereas the GH secretory response to HEXA was higher in the former than in the latter. CONCLUSIONS: Overall, the present data demonstrate that chronic HEXA treatment increases BMC and bone area at lumbar vertebrae in intact rats and at femoral diaphyses in OVX rats. The different sensitivity to HEXA of the skeletal districts examined is related to the estrogen milieu and may reflect a complex interplay between estrogens and GH/IGF function.
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Densidade Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Estrogênios/metabolismo , Hormônios/farmacologia , Oligopeptídeos/farmacologia , Animais , Osso e Ossos/efeitos dos fármacos , Feminino , Hormônios/metabolismo , Oligopeptídeos/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
We conducted a cross-sectional survey to determine the prevalence of gallstone disease (gallstone or cholecystectomy) in a random sample of the adult population of Guadalajara, Spain. The sample stratified by age and sex was drawn from the municipal census. Stratum sample sizes were proportional to population sizes and to the expected prevalence rates calculated through a meta-analysis of the European literature. The screening protocol included a gallbladder ultrasonography, a questionnaire on personal and family history, a physical examination, and a blood sample for biochemical determinations. The response rate was 61.2%. The overall prevalence of gallstone disease was 9.7% (95% CI, 7.3-12.0). Prevalence was higher (but not statistically significant) in women (11.5%; 95% CI, 8.2-14.7) than in men (7.8%; 95% CI, 4.6-11.1). After controlling for confounding by multiple logistic regression, increasing age, body mass index, dyspeptic symptoms, smoking habit, and use of hypolipidemic drugs were positively associated with gallstone disease. Total serum cholesterol and alcohol consumption were negatively associated.
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Colelitíase/epidemiologia , Adulto , Distribuição por Idade , Idoso , Índice de Massa Corporal , Colecistectomia , Colelitíase/etiologia , Colelitíase/cirurgia , Estudos Transversais , Feminino , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Reprodutibilidade dos Testes , Fatores de Risco , Distribuição por Sexo , Espanha/epidemiologiaRESUMO
In order to investigate the effects of ageing on the cerebral receptors for calcitonin (CT), we used an in vitro autoradiographic method to study the distribution of the binding sites for eel CT (eCT) in young and old rat brain. The inhibitory action of eCT on adenylyl-cyclase (AC) activity upon isolated brain cell membranes was also evaluated. The results show area-specific reduction of binding particularly in the hypothalamus and pons medulla of the old rat. The inhibitory action of eCT on AC activity was significantly reduced in the same areas, whereas in the striatum and mesencephalon no changes were observed. The parallel decrease of binding of eCT and of the inhibitory action of eCT on AC in ageing may represent a functional decline of neuronal activities during ageing.
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Adenilil Ciclases/metabolismo , Envelhecimento/metabolismo , Encéfalo/metabolismo , Calcitonina/metabolismo , Receptores de Superfície Celular/metabolismo , 1-Metil-3-Isobutilxantina/farmacologia , Animais , Autorradiografia , Encéfalo/crescimento & desenvolvimento , Calcitonina/farmacologia , Radioisótopos de Carbono , AMP Cíclico/metabolismo , Radioisótopos do Iodo , Cinética , Masculino , Especificidade de Órgãos , Ratos , Ratos Wistar , Receptores da Calcitonina , TrítioRESUMO
The presence of functional receptors for calcitonin gene-related peptide (CGRP) in the brain of adult rats and on nerve cell cultures was investigated. Neuronal and glial cultures were obtained from mesencephalons of embryos at gestational day 16. The response to CGRP was tested by measuring the adenylyl cyclase (AC) activity on isolated membranes. CGRP binding in adult rat brains was ineffective in activating AC, whereas a dose-dependent stimulation of AC activity was induced by the peptide both in neuronal and glial cultures. This effect was more pronounced in the glial cells where high affinity binding sites for CGRP were detected. The presence of functional CGRP receptors in embryonic mesencephalic cells, suggests a role for CGRP in the development of rat mesencephalon.
Assuntos
Adenilil Ciclases/metabolismo , Encéfalo/embriologia , Encéfalo/enzimologia , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Animais , Sítios de Ligação , Encéfalo/efeitos dos fármacos , Células Cultivadas , Ativação Enzimática , Masculino , Ratos , Ratos Sprague-Dawley , Distribuição TecidualRESUMO
Amylin has been reported to have bone-conserving effects. In the present study we evaluated the possible activity of the peptide on human osteoblast-like (hOB) cells in primary culture. Amylin between 10(-9) and 10(-6) M, dose-dependently stimulated cell proliferation with a maximal effect (200%) at 10(-6) M. In addition, amylin increased osteocalcin production when hOB cells were exposed to 1,25(OH)2D3 (10(-8)M) but there was a nonsignificant upward trend on alkaline phosphatase activity. The present results suggest that amylin could be included among the group of peptides endowed with osteogenic activity.
Assuntos
Amiloide/farmacologia , Osteoblastos/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Humanos , Polipeptídeo Amiloide das Ilhotas PancreáticasRESUMO
The distribution of binding site for [125I]-eel-calcitonin (ECT) to rat central nervous system, studied by an autoradiographic technique, showed concentrations of binding in the diencephalon, the brain stem and the spinal cord. Large accumulations of grains were seen in the hypothalamus, the amygdala, in the fasciculus medialis prosencephali, in the fasciculus longitudinalis medialis, in the ventrolateral part of the periventricular gray matter, in the lemniscus medialis and in the raphe nuclei. The density of grains in the reticular formation and in the nucleus tractus spinalis nervi trigemini was more moderate. In the spinal cord, grains were scattered throughout the dorsal horns. Binding of the ligand was displaced equally by cold ECT and by salmon CT(sCT), indicating that both peptides bind to the same receptors. Human CT was much weaker than sCT in displacing [125I]-ECT binding. The administration of ECT into the brain ventricles of rats dose-dependently induced a significant and long-lasting enhancement of hot-plate latencies comparable with that obtained with sCT. The antinociceptive activity induced by ECT is compatible with the topographical distribution of binding sites for the peptide and is a further indication that fish CTs are active in the mammalian brain.