Culture of 3D bioprinted bone constructs requires an increased fluid dynamic stimulation.

In vitro flow-induced mechanical stimulation of developing bone tissue constructs has been shown to favor mineral deposition in scaffolds seeded with cells directly exposed to the fluid flow. However, the effect of fluid dynamic parameters, such as shear stress (SS), within 3D bioprinted constructs is still unclear. Thus, this study aimed at correlating the SS levels and the mineral deposition in 3D bioprinted constructs, evaluating the possible dampening effect of the hydrogel. Human mesenchymal stem cells (hMSCs) were embedded in 3D bioprinted porous structures made of alginate and gelatin. 3D bioprinted constructs were cultured in an osteogenic medium assessing the influence of different flow rates (0, 0.7 and 7 ml/min) on calcium and collagen deposition through histology, and bone volume (BV) through micro-computed tomography. Uniform distribution of calcium and collagen was observed in all groups. Nevertheless, BV significantly increased in perfused groups as compared to static control, ranging from 0.35±0.28 mm3, 11.90±8.74 mm3 and 25.81±5.02 mm3 at week 3 to 2.28±0.78 mm3, 22.55±2.45 mm3 and 46.05±5.95 mm3 at week 6 in static, 0.7 and 7 ml/min groups, respectively. SS values on construct fibers in the range 10-100 mPa in 7 ml/min samples were twice as high as those in 0.7 ml/min samples showing the same trend of BV. The obtained results suggest that it is necessary to enhance the flow-induced mechanical stimulation of cell-embedding hydrogels to increase the amount of mineral deposited by hMSCs, compared to what is generally reported for the development of in vitro bone constructs. STATEMENT OF SIGNIFICANCE: In this study, we evaluated for the first time how the hydrogel structure dampens the effect of flow-induced mechanical stimulation during the culture of 3D bioprinted bone tissue constructs. By combining computational and experimental techniques we demonstrated that those shear stress thresholds generally considered for culturing cells seeded on scaffold surface, are no longer applicable when cells are embedded in 3D bioprinted constructs. Significantly, more bone volume was formed in constructs exposed to shear stress values generally considered as detrimental than in constructs exposed shear stress values generally considered as beneficial after 3 weeks and 6 weeks of dynamic culture using a perfusion bioreactor.

La osteocalcina: de marcador de formación ósea a hormona; y el hueso, un órgano endocrino / Osteocalcin: from marker of bone formation to hormone; and bone, an endocrine organ

La osteocalcina es una proteína sintetizada por el osteoblasto. Antes de ser liberada a la matriz extracelular, la osteocalcina humana sufre una gamma-carboxilación, al unirse en las posiciones 17, 21 y 24 el ácido gamma-carboxi-glutámico. A la circulación pasa parte de osteocalcina carboxilada y descarboxilada. Desde su descubrimiento a finales de los años 70, se ha utilizado como marcador de formación ósea al ser un producto osteoblástico, y desconociéndose su papel en el organismo. En estos últimos años se ha descubierto que la osteocalcina es, en realidad, una hormona, y el hueso un órgano endocrino. La osteocalcina que actúa como hormona es la forma descarboxilada. La osteocalcina interviene en la homeostasis de la glucosa, en el funcionamiento del músculo esquelético, en el desarrollo cerebral, la fertilidad masculina, la esteatosis hepática y la calcificación arterial. En realidad todos estos hechos se han probado en ratones, pero existen indicios importantes de que esto podría ocurrir en humanos. Nos encontramos ante hechos que, de probarse, tendrían una enorme trascendencia clínica. (AU)

Osteocalcin is a protein synthesized by the osteoblast. Before being released into the extracellular matrix, human osteocalcin undergoes gamma-carboxylation, as gamma-carboxy-glutamic acid binds at positions 17, 21 and 24. Part of the carboxylated and decarboxylated osteocalcin passes into the circulation. Since its discovery in the late 70s, it has been used as a marker of bone formation as it is an osteoblastic product and its role in the body is unknown. In recent years, osteocalcin has been identified as a hormone. Bone is considered an endocrine organ. Osteocalcin acting as a hormone is the decarboxylated form. Osteocalcin is involved in glucose homeostasis, skeletal muscle function, brain development, male fertility, hepatic steatosis, and arterial calcification. All of these facts have actually been tested in mice, but there is strong evidence that this could occur in humans. We are faced with facts that, if proven, would have enormous clinical significance. (AU)

Aceite de oliva y salud ósea / Olive oil and bone health

OBJETIVO: Existen en la literatura una serie de trabajos que demuestran que la incidencia de osteoporosis y fracturas asociadas es menor en países en los que la dieta mediterránea es predominante. El aceite de oliva es la principal característica común de toda la dieta mediterránea suponiendo un tercio de la ingesta de grasas vegetales. Se ha realizado una amplia revisión de trabajos que demuestran que la ingesta de aceite de oliva, tanto en animales de experimentación, en especial ratas ovariectomizadas, como en humanos, produce acciones positivas sobre el hueso. Se han revisado los efectos de diferentes componentes del aceite de oliva virgen como la oleuropeína, un compuesto fenólico, y otros alcoholes fenólicos como el tirosol y el hidrotirosol. La oleuropeína no sólo ejerce acciones sobre el hueso de ratas ovariectomizadas, sino que produce acciones sobre la formación de osteoblastos y desciende la formación de células "osteoclasto-like". Los compuestos fenólicos del aceite de oliva han demostrado ejercer acciones anti-oxidantes in vitro e in vivo. El tirosol y el hidrotirosol ejercen acciones sobre la pérdida de hueso en ratas ovariectomizadas e inhiben la formación de osteoclastos de modo dosis-dependiente. Un trabajo realizado por nuestro grupo ha demostrado que el aceite de oliva virgen ejerce también acciones sobre los parámetros biomecánicos del hueso como el módulo de Young y la dimensión fractal en ratas ovariectomizadas. Los resultados de esta revisión muestran que el aceite de oliva ejerce una acción positiva sobre la salud ósea. Sus componentes poseen propiedades anti-oxidantes y anti-inflamatorias, siendo candidatos potenciales para la prevención de la osteoporosis

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Efectos del tratamiento con bazedoxifeno sobre la calidad ósea en ratas ovariectomizadas / Effects of bazedoxifene treatment on the bone quality of ovariectomized rats

OBJETIVO: El bazedoxifeno es un SERM de 3ª generación con efectos agonistas sobre el hueso y sobre el útero y el tejido mamario. Nuestro objetivo ha sido estudiar los efectos del bazedoxifeno sobre la calidad ósea en un modelo experimental de ratas ovariectomizadas. MATERIAL Y MÉTODOS: Se utilizaron 3 grupos de 15 ratas Wistar hembras de 6 meses de edad: uno control; otro de ratas ovariectomizadas; y un tercer grupo de ratas ovariectomizadas tratadas con bazedoxifeno (0,33 mg/kg/día). Tras 8 meses se estudiaron la densitometría ósea lumbar y femoral, los parámetros microtomográficos, los marcadores bioquímicos de remodelado y los parámetros biomecánicos del hueso. RESULTADOS: La ovariectomía descendió la densidad ósea femoral y lumbar. La última se recuperó parcialmente con bazedoxifeno. El remodelado óseo aumentó, recuperando el bazedoxifeno los niveles de formación. El bazedoxifeno recuperó la fracción volumétrica ósea (BV/TV), la densidad de superficie ósea (BS/TV), el aumento en la separación trabecular (Tb. Sp), la disminución en el número de trabéculas (Tb. N), el aumento del factor de patrón trabecular (Tb. Pf) y el índice de modelo estructural (SMI). La superficie relativa cortical aumentó tras la ovariectomía, normalizándose con bazedoxifeno. También recuperó la deformación máxima antes de la rotura producida por la ovariectomía, y amortiguó parcialmente la ganancia de peso de las ratas ovariectomizadas. CONCLUSIONES: Nuestro estudio muestra resultados positivos del bazedoxifeno sobre la calidad ósea. Este fármaco podría estar especialmente indicado para mujeres jóvenes postmenopáusicas con osteoporosis o en riesgo de padecerla

OBJETIVE: Bazedoxifene is a 3rdgeneration SERM with agonistic effects on the bones, uterus and breast tissue. Our goalhas been to study the effects of bazedoxifene on bone quality of an experimental group of ovariectomized rats. MATERIAL AND METHODS:3 groups of 15 6‐month‐old Wistar female rats were used: a control group, a group of untreatedovariectomized rats and a group of ovariectomized rats treated with bazedoxifene (0.33 mg/kg/day). After 8 monthswe studied the lumbar and femur bone densitometry, the microtomographic parameters, the biochemical markers forbone remodelling and the bone biomechanical parameters. RESULTS:The ovariectomy depleted the femur and lumbar bone density. After receiving bazedoxifene, the lumbar bonedensity showed partial healing. Bone remodelling increased recovering bazedoxifene formation levels. Bazedoxifenepromoted the recovery of the bone volume fraction (BV/TV), the bone surface density (BS/BV), the trabecular number(Tb. N), the trabecular spacing (Tb. Sp), the trabecular pattern factor (Tb. Pf) and the structural model index (SMI). Thecortical surface increased after the ovariectomy and returned to normal levels with the administration of bazedoxifene. The maximum deformation showed before the ovariectomy was also restored, partially cushioning the ovariectomizedrats' weight gain. CONCLUSIONS:Our study has shown bazedoxifene positive results on bone quality. This specific drug could be particularlysuitable for young postmenopausal women suffering or at risk of suffering osteoporosis

Effects of Cyclosporine, Tacrolimus, and Rapamycin on Osteoblasts.

PURPOSE: One factor that can contribute to severe bone loss after transplantation is the direct action of immunosuppressants on bone cells. The aim of this work was to study the effects of cyclosporine (CsA), tacrolimus (FK-506), and rapamycin (RAPA) on the release of three local factors directly implicated in bone-remodeling regulation and apoptosis of human osteoblasts: interleukin (IL)-6, osteoprotegerin, and receptor activator of nuclear factor κß (RANKL). BASIC PROCEDURES: Human osteoblasts were obtained from five different patients who underwent orthopedic surgery. These cells were treated with what are considered to be a clinically high dose and an acceptable dose of each immunosuppressant-RAPA 50 ng/mL and 12 ng/mL, FK-506 20 ng/mL and 5 ng/mL, CsA 1000 ng/mL and 250 ng/mL-or vehicle. Apoptotic cell death was quantified using flow cytometry of DNA content in permeabilized, propidium iodide-stained cells. IL-6 was measured using enzyme-linked immunosorbent assay (ELISA; Quantikine Human IL6, R&D Systems, Minneapolis, Minn, United States). Messenger RNA (mRNA) expression of osteoprotegerin, RANKL, and IL-6 was measured using quantitative RT-PCR. MAIN FINDINGS: A significant increase in IL-6 (mRNA and released protein) was observed in the presence of FK-506 and RAPA. Addition of RAPA to the cultures of osteoblasts produced a significant increase in the OPG/RANKL ratio. A significant increase in osteoblast apoptosis was observed in the cells treated with FK-506 and RAPA 24 hours after the addition of immunosuppressants. CsA did not produce any significant changes in osteoblasts. PRINCIPAL CONCLUSIONS: These results suggest that an increase in osteoblast apoptosis by osteoblasts may be one of the mechanisms by which bone loss occurs after RAPA and FK-506 treatments.

Hiperparatiroidismo secundario al déficit de vitamina D / Secondary hyperparathyroidism due to vitamin D deficiency

Introducción: Cada vez está más demostrado el papel de la vitamina D en múltiples patologías, una de ellas el desarrollo de un hiperparatiroidismo secundario al déficit de vitamina D. Los métodos de laboratorio de cuantificación de vitamina D en suero no estaban bien estandarizados hasta ahora, por lo que no podía establecerse con certeza a partir de qué niveles de vitamina D se producían determinadas anomalías como la elevación de la PTH. Nuestro estudio pretende determinar por debajo de qué niveles de vitamina D nos encontraremos con niveles de PTH anormalmente elevados, realizando la determinación de vitamina D en el laboratorio con una técnica debidamente estandarizada y fiable. Métodos: El estudio descriptivo y retrospectivo se realizó con pacientes mayores de 18 años en los que se hicieron simultáneamente determinaciones de PTH, 25(OH) vitamina D (25OHD) y que además tuvieran valores normales de calcio, filtrado glomerular y fósforo. Para la determinación de vitamina D se utilizó un método de electroquimioluminiscencia estandarizado con respecto a la técnica de gases-masas. Por el programa estadístico Stava versión 11 se calculó el valor de 25OHD para el que la PTH se elevaba por encima de 70 pg/ml con la mayor sensibilidad y especificidad. Resultados: Se incluyeron 4.083 pacientes, de los que 2.858 eran mujeres (70%) y 1.225 (30%) varones. La edad media de la población estudiada fue 60,60 años (desviación estándar, 15,29). El 74% de la población tenía una PTH en suero por debajo de 70 pg/ml (valores considerados normales) y el 26% mayor de 70 pg/ml. Al construir la curva de ROC de los niveles de 25OHD, en función de valores de PTH por debajo o por encima de 70 pg/ml, el área bajo la curva fue 0,5962 (p<0,0001). El punto de corte teniendo en cuenta conjuntamente la sensibilidad y la especificidad que determinaban los valores de vitamina D para predecir los valores de PTH por encima de 70 pg/ml fue 24 ng/ml. De los pacientes con PTH normal, el 71% tenían valores de vitamina D normales, mientras que, de los pacientes con PTH elevada (mayor de 70 pg/ml), casi la mitad presentaban una vitamina D menor de 24 ng/ml, porcentaje que aumentaba según se iba elevando la PTH. Conclusiones: El valor de 25OHD que muestra una mejor especificidad y sensibilidad para predecir valores anormalmente elevados de PTH es 24 ng/ml, valor superior al presentado en trabajos anteriores (alrededor de 18 ng/ml). Con los resultados de este estudio, realizado con un método debidamente calibrado, se puede decir que el 44,9% de pacientes con valores de vitamina D menores de 24 ng/ml presenta niveles de PTH anormalmente elevados, con una función renal normal y valores de calcio y fósforo normales. Este porcentaje es menor entre los 18 y 40 años (24%) y llega al 49% por encima de los 60 años. Estos pacientes podrían tratarse con vitamina D para evitar un posible hiperparatiroidismo secundario al déficit de dicha vitamina. Es importante tener en cuenta que el método de determinación de vitamina D utilizado debe estar debidamente estandarizado con respecto al método de gases-masas (AU)

Introduction: Vitamin D is increasingly recognized as playing a significant role in combatting many diseases. One is the development of secondary hyperthyroidism due vitamin D deficiency. To date, laboratory quantification methods of serum vitamin D were not well standardized. It could not be established with certainty from which levels of vitamin D certains abnormalities take place, like an elevation of PTH. The present study was aimed at determining below what vitamin D levels we will find abnormally high levels of PTH, carrying out the vitamin D determination in the laboratory with a standardized, reliable technique. Methods: This descriptive, retrospective study was conducted with patients over 18 years in which determinations were made simultaneously with PTH, 25 (OH) vitamin D (25OHD) and which also have normal values of calcium, glomerular filtration rate and phosphorus. For determining vitamin D, standardized electrochemiluminescence method was used with gas chromatography- mass spectrometry method. Using the Stava version 11 statistical program, the 25OHD was calculated where PTH value was above 70 pg/ml with greater sensitivity and specificity. Results: In all, 4,083 patients were included, of whom 2,858 were women (70%) and 1,225 (30%) males. The mean age of the study population was 60.60 years (standard deviation, 15.29). 74% of the population had a serum PTH under 70 pg/ml (normal values) and 26% had a serum PTH higher tan 70 ng/ml. By constructing the ROC curve levels of 25OHD, depending on PTH values below or above 70 pg/ml, the area under the curve was 0.5962 (p<0.0001). The cut having jointly account the sensitivity and specificity that determined vitamin D levels to predict PTH values above 70 pg/ml was 24 ng/ml. Of the patients with normal PTH, 71% presented normal vitamin D values, while patients with elevated PTH (Greater than 70 pg/ml), almost half had a vitamin D below 24 ng / ml, which increased as the PTH percentage was elevated. Conclusions: The 25OHD value that presents better specificity and sensitivity to predict abnormally high PTH is 24 ng/ml, which is higher than the level reported in previous work, (about 18 ng/ml) value. The results of this study, carried out with an appropriately calibrated method, showed that 44.9% of patients with vitamin D values of less than 24 ng/ml PTH had abnormally high levels, with a normal value of calcium and phosphorus and normal renal function. This percentage is less in those individuals between 18 and 40 years (24%) and reaches 49% beyond 60 years. These patients could be treated with vitamin D to prevent possible secondary hyperparathyroidism due to vitamin deficiency. It is noteworthy that the method of determining vitamin D used must be properly standardized with respect to gas chromatography-tandem mass spectrometry method (AU)

Expression of bone markers and micro-CT analysis of alveolar bone during orthodontic relapse.

OBJECTIVES: To investigate biological changes in alveolar bone occurring during orthodontic relapse. MATERIALS AND METHODS: Rat maxillary first molars were moved mesially for 10 days. After orthodontic tooth movement (OTM), appliances were removed, and the molars were allowed to relapse for one, three, five, seven, 14 or 21 days. Changes in 3D morphometric parameters of bone located mesial to the first molars were evaluated by micro-CT. Total RNA was isolated from the same bone site, and real-time RT-PCR was used to measure the expression of bone formation and resorption markers. RESULTS: One day after appliance removal, the molars relapsed to a mean 73% of the achieved OTM and then steadily relapsed to 93% at 21 days. Tissue mineral density and per cent bone volume increased over the experimental period. Inversely, there was a decrease in total porosity. Gene expression of OCN, Coll-I and ALP decreased during OTM, whilst as the molars relapsed showed tended to increase. Gene expression of RANKL and TRAP increased during OTM. Changes in mRNA expression of H(+)-ATPase were minor. By 21 days post-appliance removal, the remodelling process in rats appeared to have returned to control levels. CONCLUSIONS: Bone tissue reactions on a molecular level are similar during OTM and orthodontic relapse. These findings validate the importance of immediate retention following active OTM.

Effect of TiO2 scaffolds coated with alginate hydrogel containing a proline-rich peptide on osteoblast growth and differentiation in vitro.

The aim of this study was to investigate the effect of TiO2 scaffold (SC) coated with an alginate hydrogel containing a proline-rich peptide (P2) on osteoblast proliferation and differentiation in vitro. Peptide release was evaluated and a burst release was observed during the first hours of incubation, and then progressively released overtime. No changes were observed in the cytotoxicity after 48 h of seeding MC3T3-E1 cells on the coated and uncoated TiO2 SC. The amount of cells after 7 days was higher on uncoated TiO2 SC than on alginate-coated TiO2 SC, measured by DNA content and scanning electron microscope imaging. In addition, while lower expression of integrin beta1 was detected for alginate-coated TiO2 SC at this time point, similar gene expression was observed for other integrins, fibronectin-1, and several osteoblast differentiation markers. After 21 days, gene expression of integrin beta3, fibronectin-1, osterix, and collagen-I was increased in alginate-coated compared to TiO2 SC. Moreover, increased gene expression of integrin alpha8, bone morphogenetic protein 2, interleukin-6, and collagen-I was found on P2 alginate-coated TiO2 SC compared to alginate-coated TiO2 SC. In conclusion, our results indicate that alginate-coated TiO2 SC can act as a matrix for delivery of proline-rich peptides increasing osteoblast differentiation. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.

Risk in dosing regimens for 25-OH vitamin D supplementation in chronic haemodialysis patients.

INTRODUCTION: 25-OH vitamin D (25-OHvitD) insufficiency or deficiency should be treated in haemodialysis (HD) patients, although the 25-OHvitD target, drug or dosing regimens are unclear. AIMS: To describe factors associated with 25-OHvitD levels in HD patients and to assess the effect of three dosing regimens to supplement 25-OHvitD (calcifediol) on serum calcium (Ca), phosphate (P), parathyroid hormone (PTH), 25-OHvitD and 1,25-OHvitD. METHODS: Two hundred and seventeen patients from three HD units were studied. Demographic and biochemical data were collected at baseline. Two different 25-OHvitD assays were used. One hundred and sixty-seven patients were treated with various calcifediol dosing regimens. The same biochemical determinations were repeated after 3 months of treatment. RESULTS: At baseline, 12.9% of patients had 25-OHvitD <10 ng/ml. In multivariate linear regression, the season (lower in winter) and the assay method were determinants of 25-OHvitD concentration. Following calcifediol supplementation, 25-OHvitD, calcium and phosphate increased, while PTH diminished with statistical significance. After treatment, there were positive correlations between 25-OHvitD and Ca (r = 0.28, p < 0.0001) or 1,25-OHvitD (r = 0.75, p < 0.0001) that were not observed in the baseline dataset. High concentrations of post-treatment 25-OHvitD were associated with higher 1,25-OHvitD levels. Calcemia increased more in those treated with concomitant active vitamin D or those having suppressed baseline PTH, while PTH decreased more in those having above-target PTH levels. CONCLUSIONS: Standardisation of methods to determine 25-OHvitD blood levels is needed. In HD patients, calcifediol increased 25-OHvitD, calcemia and phosphatemia and lowered PTH. Caution should be exercised with the higher calcifediol dosing regimens, especially in patients with suppressed PTH or on vitamin D receptor activators.

Effect of alginate hydrogel containing polyproline-rich peptides on osteoblast differentiation.

Polyproline-rich synthetic peptides have previously been shown to induce bone formation and mineralization in vitro and to decrease bone resorption in vivo. Alginate hydrogel formulations containing these synthetic peptides (P2, P5, P6) or Emdogain® (EMD) were tested for surface coating of bone implants. In an aqueous environment, the alginate hydrogels disclosed a highly compact structure suitable for cell adhesion and proliferation. Lack of cytotoxicity of the alginate-gel coating containing peptides was tested in MC3T3-E1 cell cultures. In the present study, relative mRNA expression levels of integrin alpha 8 were induced by P5 compared to untreated alginate gel, and osteopontin mRNA levels were increased after 21 days of culture by treatment with synthetic peptides or EMD compared to control. Further, in agreement with previous results when the synthetic peptides were administered in the culture media, osteocalcin mRNA was significantly upregulated after long-term treatment with the formulated synthetic peptides compared to untreated and EMD alginate gel. These results indicate that the alginate gel is a suitable carrier for the delivery of synthetic peptides, and that the formulation is promising as biodegradable and biocompatible coating for bone implants.

Compatibilidad física del bicarbonato sódico con fármacos de uso frecuente en la unidad de cuidados intensivos / Physical compatibility of sodium bicarbonate with other drugs often administered in the intensive care unit

Introducción Las alteraciones acidobásicas se asocian a muchas afecciones del paciente crítico. Estos trastornos metabólicos requieren pronta normalización mediante bicarbonato sódico. Esta solución electrolítica alcalinizante se administra en infusión continua o intermitente. Se ha descrito su incompatibilidad por su pH alcalino, que produce precipitación de carbonatos insolubles y origina gases de dióxido de carbono al mezclarlo en soluciones ácidas. Objetivo Determinar la compatibilidad física del bicarbonato sódico 1M administrado en Y con fármacos de uso común en UCI.Material y método Estudio experimental in vitro. Se mezcló el bicarbonato con 13 fármacos simulando la administración en Y. Se combinaron 5 ml de bicarbonato con 5 ml de cada fármaco, eligiéndose concentraciones máximas utilizadas en la práctica. Las muestras se examinaron visualmente para detectar cambios de color, turbidez, precipitación o formación de gas; medición del pH y análisis espectrofotométrico a 450 nm y 620 nm. Se evaluaron las muestras a 0, 15, 30, 60 y 120 min. Los criterios de compatibilidad fueron: ausencia de cambios visuales, cambio pH<0,5 y variabilidad de absorbancia < 0,01.ResultadosSe estudiaron los fármacos individualmente y en mezcla con el bicarbonato, y resultaron 27 muestras, con las que se realizaron 135 determinaciones. Las incompatibilidades no siempre producen cambios visuales. Conocer el pH de los fármacos no garantiza la compatibilidad de la mezcla. La nitroglicerina con pH 4 es compatible. El tiopental con pH 11 precipita. Las absorbancias elevadas se acompañan de cambios de color, turbidez y precipitación.Conclusiones El bicarbonato es físicamente compatible con esmolol, furosemida, heparina, insulina, morfina, nimodipino, nitroglicerina y urapidil e incompatible con amiodarona, cisatracurio, haloperidol, midazolam y tiopental (AU)

Introduction Acid-base disorders are associated with many diseases of the critically ill patient. Early treatment with sodium bicarbonate of these metabolic disorders is required for their normalization. This is an alkaline electrolyte solution administered by continuous or intermittent infusion. Its incompatibility due to its alkaline pH has been described, as it produces insoluble carbonate precipitation and causes carbon dioxide gas when mixed with acidic solutions. Material and method An in vitro experimental study was performed. Bicarbonate was mixed with 13 drugs simulating Y-site administration. We combined 5ml bicarbonate with 5ml of every drug, at highest daily concentration used. The samples were visually examined to detect color changes, cloudiness, precipitation or gas formation, pH measurement and spectrophotometric analysis at 450nm and 620nm. The samples were evaluated at 0, 15, 30, 60 and 120minutes. The compatibility criteria were absence of visual changes, pH changes<0.5 and variability of absorbance <0.01.ResultsWe studied each drug individually and mixed with bicarbonate with 27 samples, and 135 measurements were performed. The incompatibilities did not always produce visual changes. Knowing the pH of drugs does not guarantee the compatibility of the mixture. Nitroglycerin with pH 4 is compatible with bicarbonate. Thiopental with pH 11 makes precipitation. Higher absorbances showed color changes, cloudiness and precipitation. Conclusions Bicarbonate is physically compatible with esmolol, furosemide, heparin, insulin, morphine, nimodipine, nitroglycerin and urapidil and incompatible with amiodarone, cisatracurium, haloperidol, midazolam and thiopental (AU)

[Physical compatibility of sodium bicarbonate with other drugs often administered in the intensive care unit]. / Compatibilidad física del bicarbonato sódico con fármacos de uso frecuente en la unidad de cuidados intensivos.

INTRODUCTION: Acid-base disorders are associated with many diseases of the critically ill patient. Early treatment with sodium bicarbonate of these metabolic disorders is required for their normalization. This is an alkaline electrolyte solution administered by continuous or intermittent infusion. Its incompatibility due to its alkaline pH has been described, as it produces insoluble carbonate precipitation and causes carbon dioxide gas when mixed with acidic solutions. MATERIAL AND METHOD: An in vitro experimental study was performed. Bicarbonate was mixed with 13 drugs simulating Y-site administration. We combined 5 ml bicarbonate with 5 ml of every drug, at highest daily concentration used. The samples were visually examined to detect color changes, cloudiness, precipitation or gas formation, pH measurement and spectrophotometric analysis at 450 nm and 620 nm. The samples were evaluated at 0, 15, 30, 60 and 120 minutes. The compatibility criteria were absence of visual changes, pH changes<0.5 and variability of absorbance <0.01. RESULTS: We studied each drug individually and mixed with bicarbonate with 27 samples, and 135 measurements were performed. The incompatibilities did not always produce visual changes. Knowing the pH of drugs does not guarantee the compatibility of the mixture. Nitroglycerin with pH 4 is compatible with bicarbonate. Thiopental with pH 11 makes precipitation. Higher absorbances showed color changes, cloudiness and precipitation. CONCLUSIONS: Bicarbonate is physically compatible with esmolol, furosemide, heparin, insulin, morphine, nimodipine, nitroglycerin and urapidil and incompatible with amiodarone, cisatracurium, haloperidol, midazolam and thiopental.

Daily or monthly ibandronate prevents or restores deteriorations of bone mass, architecture, biomechanical properties and markers of bone turnover in androgen-deficient aged rats.

AIM: The aim of this study was to investigate the effects of the bisphosphonate ibandronate (IBN) in a male osteoporosis animal model. METHODS: Two studies were performed in 9-month-old orchidectomised (ORX) or sham-operated rats. In prevention study, subcutaneous IBN was administered daily (1 µg/kg) or monthly (28 µg/kg every 28 days) starting on day of surgery for 5 months. In treatment study, the same treatment started 6 months after ORX. After sacrifice, bone analyses by dual-energy X-ray absorptiometry, 3-dimensional micro-computed tomography, and 3-point bending were performed in femora or vertebrae. Serum tartrate-resistant acid phosphatase 5b (TRAP-5b) and aminoterminal propeptide of collagen I (PINP) were analysed for resorption and osteocalcin (BGP) for bone formation. RESULTS: In both studies, ORX resulted in significant femoral and vertebral bone loss and microarchitectural deterioration after 5 months of ORX, and became more pronounced after 11 months. Biomechanical strength was also decreased. Serum levels for TRAP-5b and BGP increased while PINP levels were reduced or unchanged. Both daily and monthly IBN prevented or even restored ORX-induced changes in both studies, with the intermittent regimen showing a improvement in efficacy with respect to many of the biomechanical parameters.

Compatibilidad visual y física de la furosemida en mezclas intravenosas para perfusión continua / Physical compatibility of furosemide in intravenous mixtures for continuous perfusion

IntroducciónLos pacientes ingresados en las UCI reciben simultáneamente numerosos fármacos, con una disponibilidad de accesos venosos limitada que obliga a infundir conjuntamente varias perfusiones a través de una misma luz del catéter. La furosemida es una solución sin capacidad tamponante que precipita con facilidad. A pesar de la recomendación de la ficha técnica de que no debe infundirse con otros medicamentos, existen estudios en la bibliografía que demuestran su compatibilidad físicoquímica con otros fármacos. No obstante, las concentraciones estudiadas no siempre coinciden con las utilizadas en la práctica clínica.ObjetivosEstudiar y verificar la compatibilidad física de la furosemida en mezcla i.v.Material y métodoEstudio experimental in vitro en el que se procedió a mezclar la furosemida con 12 fármacos a proporción 1:1 obteniendo un total de 40 muestras evaluándose a distintos tiempos (minutos 0–15–30–60–120) las siguientes variables: pH de la mezcla, determinación de cambios en el color, turbidez y precipitación. Para ello se emplearon métodos de observación visuales, medición del pH y absorción por espectrofotometría a 450–620nm.ResultadosSe realizaron un total de 40 muestras, 13 simples, 12 dobles y 15 triples. Fueron compatibles aquellas mezclas que no presentaron cambios físicos, variación en el pH y cambios en los valores de absorbancia.ConclusiónLa furosemida es compatible físicamente con las soluciones de bicarbonato, heparina, insulina, morfina, nitroglicerina, nimodipino y tiopental e incompatible con amiodarona, cisatracurio, haloperidol, midazolam y urapidil (AU)

IntroductionPatients in the intensive care units simultaneously receive concomitantly many drugs, with limited venous accesses. Thus, several different perfusions must be administered jointly through the same catheter. Furosemide is a solution with no buffer capacity that is easily precipitated. In spite of the recommendation on its data sheet stating that it should not be used with other drugs, studies found in the bibliography suggest that it has physicochemical compatibility with other drugs. However, the concentrations studied do not always coincide with those used in the clinical practice.ObjectivesTo study and verify the physical compatibility of furosemide in intravenous mixture.Material and methodAn experimental study in vitro, in which furosemide was mixed with 12 drugs at a 1:1 proportion was performed. A total of 40 samples were obtained and the following variables were evaluated at different intervals, 0, 15, 30, 60 and 120min: ph of mixture, color changes, presence of turbidity and precipitation. To do so, visual observation procedures, ph measurements and spectrophotometer absorption at 450 and 620nm were used.ResultsForty samples, 13 simples, 12 doubles and 15 triples, were obtained. Those mixtures that did not show physical changes, pH variation and absorption variation were considered compatible.ConclusionFurosemide is physically compatible with bicarbonate solution, heparin, insulin, morphine and nitroglycerin and incompatible with amiodarone, cisatracurium, haloperidol, midazolam and urapidil (AU)

[Physical compatibility of furosemide in intravenous mixtures for continuous perfusion]. / Compatibilidad visual y física de la furosemida en mezclas intravenosas para perfusión continua.

INTRODUCTION: Patients in the intensive care units simultaneously receive concomitantly many drugs, with limited venous accesses. Thus, several different perfusions must be administered jointly through the same catheter. Furosemide is a solution with no buffer capacity that is easily precipitated. In spite of the recommendation on its data sheet stating that it should not be used with other drugs, studies found in the bibliography suggest that it has physicochemical compatibility with other drugs. However, the concentrations studied do not always coincide with those used in the clinical practice. OBJECTIVES: To study and verify the physical compatibility of furosemide in intravenous mixture. MATERIAL AND METHOD: An experimental study in vitro, in which furosemide was mixed with 12 drugs at a 1:1 proportion was performed. A total of 40 samples were obtained and the following variables were evaluated at different intervals, 0, 15, 30, 60 and 120 min: ph of mixture, color changes, presence of turbidity and precipitation. To do so, visual observation procedures, ph measurements and spectrophotometer absorption at 450 and 620 nm were used. RESULTS: Forty samples, 13 simples, 12 doubles and 15 triples, were obtained. Those mixtures that did not show physical changes, pH variation and absorption variation were considered compatible. CONCLUSION: Furosemide is physically compatible with bicarbonate solution, heparin, insulin, morphine and nitroglycerin and incompatible with amiodarone, cisatracurium, haloperidol, midazolam and urapidil.

Differentiation of Y chromosome in the X(1)X(1)X(2)X(2)/X(1)X(2)Y sex chromosome system of Hoplias malabaricus (Characiformes, Erythrinidae).

Six populations of Hoplias malabaricus from the Lower Paranapanema River were studied and showed 2n = 40 with metacentric/submetacentric chromosomes for females and 2n = 39 with m/sm chromosomes for males, thereby revealing a multiple sex chromosome system of the X(1)X(1)X(2)X(2)/X(1)X(2)Y type. The Y chromosome was the largest metacentric chromosome in all karyotypes. The heterochromatic blocks were located in a pericentromeric region of all pairs and in telomeric regions in some other pairs. A conspicuous pericentromeric C-band was detected in a single pair, equivalent to the X(1) chromosome. No markers on X(2) chromosomes were detected, but they could be identified by their size. The females displayed the same distribution of C and chromomycin A(3) bands and 18S rDNA sites among the populations. However, the males exhibited differences in both number and position of Giemsa C-bands on the Y chromosome, which were also evident after Chromomycin A(3) banding and FISH with the 18S rDNA probe. These cytogenetic tools allowed for the identification of possible mechanisms involved in the differentiation and evolution of the Y chromosome.

[Perception of privacy in patients hospitalized in an Intensive Care Unit]. / Percepción de la intimidad en pacientes hospitalizados en una Unidad de Cuidados Intensivos.

INTRODUCTION: The Intensive Care Unit (ICU) is an impersonal and technologically invasive setting. The rules and framework of the unit favor a lack of privacy, an inherent fact for every kind of hospitalization. The objectives of the study are to know the experience of patients admitted to the ICU in relation to the perception of privacy and its impact on their own experience. MATERIAL AND METHODS: Phenomenological qualitative methodology. The participants were patients admitted to the ICU of Son Dureta University Hospital in Palma de Mallorca, who were older than 18 with a minimum stay of 48 hours and who had signed an informed consent. Data collection. By exhaustive semi-structured interviews. Content analysis. RESULTS: The perception of privacy in patients admitted to the ICU is described in relationship with surrounding physical space, family setting and privacy autonomy. The patients evaluated the flexibility of rules, professionalism of the nursing staff and the need for family support when the situation is more stable. CONCLUSION: To prevent the quality of nursing cares from only depending on their technological knowledge and ability, but also depends on the humane side of caring, it is extremely important to consider the different elements that mould the experience of being admitted to the ICU and respect of the privacy of each person.

Percepción de la intimidad en pacientes hospitalizados en una Unidad de Cuidados Intensivos / Perception of privacy in patients hospitalized in an Intensive Care Unit

Introducción. La Unidad de Cuidados Intensivos(UCI) es un entorno impersonal y tecnológicamenteinvasivo. La normativa de la unidad y la estructuraarquitectónica favorecen la pérdida de intimidad,hecho que resulta inherente a toda hospitalización.Los objetivos del estudio son conocer la experienciade los pacientes ingresados en UCI en relación a lapercepción de intimidad y el impacto de esta sobresu experiencia.Material y métodos. Metodología cualitativafenomenológica. Los participantes fueron lospacientes ingresados en la UCI del HospitalUniversitario Son Dureta de Palma de Mallorca,mayores de 18 años, con una estancia mínima de 48horas tras consentimiento informado. Recogida dedatos: entrevistas semiestructuradas en profundidad.Análisis de contenido.Resultados. Se describe que la percepción de laintimidad en los pacientes ingresados en UCI serelaciona con el espacio físico que les rodea, elentorno familiar y la privacidad de autonomía. Lospacientes valoran la flexibilidad de las normas, laprofesionalidad del personal de enfermería y lanecesidad de apoyo familiar cuando la situación esmás estable.Conclusión. Con el fin de que la calidad de loscuidados enfermeros de las UCI no dependaúnicamente de los conocimientos y habilidadestecnológicos, sino que se caracterice por lahumanización de los mismos, es de suma importanciala consideración de los diferentes elementos quemodulan la experiencia de estar ingresado en unaUCI y el respeto a la intimidad de la persona

Introduction. The Intensive Care Unit (ICU) is animpersonal and technologically invasive setting.The rules and framework of the unit favor a lack ofprivacy, an inherent fact for every kind ofhospitalization. The objectives of the study are to know the experience of patients admitted to theICU in relation to the perception of privacy and itsimpact on their own experience.Material and methods. Phenomenologicalqualitative methodology. The participants werepatients admitted to the ICU of Son DuretaUniversity Hospital in Palma de Mallorca, whowere older than 18 with a minimum stay of 48hours and who had signed an informed consent.Data collection. By exhaustive semi-structuredinterviews. Content analysis.Results. The perception of privacy in patientsadmitted to the ICU is described in relationshipwith surrounding physical space, family setting andprivacy autonomy. The patients evaluated theflexibility of rules, professionalism of the nursingstaff and the need for family support when thesituation is more stable.Conclusion. To prevent the quality of nursing caresfrom only depending on their technologicalknowledge and ability, but also depends on thehumane side of caring, it is extremely important toconsider the different elements that mould theexperience of being admitted to the ICU and respectof the privacy of each person

Well-being, appraisal, and coping in Latina and Caucasian female dementia caregivers: findings from the REACH study.

While there has been considerable interest in studying ethnically diverse family caregivers, few studies have investigated the influence of dementia caregiving on Latino families. The current study includes participants from two sites of the REACH (Resources for Enhancing Alzheimer's Caregiver Health) project to compare well-being, appraisal, and religiosity by ethnicity, with specific attention to levels of acculturation. Latina (n = 191) and Caucasian female (n = 229) dementia family caregivers from two regions of the United States (Miami, Florida and Northern California) were compared at baseline on demographics, care recipient characteristics, mental and physical health, and psychosocial resources, including appraisal style and religiosity. Latina caregivers reported lower appraisals of stress, greater perceived benefits of caregiving, and greater use of religious coping than Caucasian caregivers. The relationship of these variables to level of acculturation for the Latina caregivers was also explored. Implications of these results for psychosocial interventions with Latino and Caucasian family caregivers are discussed.

An evaluation of the NINCDS-ADRDA neuropsychological criteria for the assessment of Alzheimer's disease: a confirmatory factor analysis of single versus multi-factor models.

Neuropsychological test batteries are frequently used to assess the nature and severity of cognitive deficits among patients with early Alzheimer's Disease (AD) and related disorders. The NINCDS-ADRDA criteria are among the most widely used guidelines to diagnose dementia (McKhann et al.,1984). These criteria specify eight distinct areas of neuropsychological function that should be evaluated in patients with suspected cognitive impairment. Recent studies have suggested that neuropsychological deficits observed in AD may be explained by a single general factor related to memory deficits or to executive dysfunction. In contrast, the results of other investigations have indicated that multiple qualitatively different factors underlie cognitive abilities in AD. In the present study, we used confirmatory factor analysis to examine the structure of cognitive abilities in AD and to assess the extent to which single and multiple ability factors accurately represent neuropsychological test data obtained from patients with AD. Results indicated that the NINCDS-ADRDA model fit the data better than a single factor model. However, a more parsimonious model specifying memory, verbal abilities, visuospatial skills, executive function, and higher as well as lower functional activities of daily living fit the data better than the NINCDS-ADRDA model. These results have important theoretical and practical implications for diagnostic evaluation.