Case Report: Everolimus reduced bone turnover markers but showed no clinical benefit in a patient with severe progressive osseous heteroplasia.

Background: Progressive osseous heteroplasia (POH) is an ultrarare genetic disorder characterized by an inactivating mutation in the GNAS gene that causes heterotopic ossification. Inhibition of the mammalian target of the rapamycin (mTOR) signalling pathway has been proposed as a therapy for progressive bone fibrodysplasia and non-genetic forms of bone heteroplasia. Herein, we describe the impact of using Everolimus as a rescue therapy for an identical twin girl exhibiting an aggressive clinical phenotype of POH. Methods: Clinical evaluation of the progression of the disease during Everolimus treatment was performed periodically. Cytokine markers involved in bone metabolism and protein markers related to bone activity were analyzed to explore bone turnover activity. Results: The patient received Everolimus therapy for 36 weeks. During treatment, no clinical improvement of the disease was perceived. Analysis of biochemical parameters, namely, ß-CTX (r 2 = -0.576, P-value = 0.016) and PNIP (r 2 = -0.598, P-value = 0.011), indicated that bone turnover activity was significantly reduced. Additionally, bone metabolism-related biomarkers showed only a significant positive correlation with PTH levels. Conclusions: Everolimus treatment did not modify the clinical progression of the disease in an aggressive form of POH, although an impact on the protein markers studied was observed.

Evolution of physical-chemical parameters, microbial diversity and VOC emissions of olive oil mill waste exposed to ambient conditions in open reservoirs.

In the olive oil extraction process, 20% olive oil is obtained. About 80% corresponds to waste, mainly alperujo and orujo. When these residues are stored in open reservoirs for later stabilization or potential reuse, odorous Volatile Organic Compounds (VOCs) are generated as products of waste decomposition. In this work, these emissions were studied by means of TD-GC/MS in relation to the changes in the physical-chemical (ashes, moisture, total phenols, pH, proteins, fibers, oils, fats) and biological parameters (bacterial and fungal diversity in Illumina platform) of waste for 6 months. The dynamics of these parameters were statistically related to the evolution of environmental variables (temperature, relative humidity, precipitation) and their effects on the most relevant physical-chemical parameters in order to evaluate their incidence in odorant VOCs emissions over time. The results showed a progressive increase in the diversity of both fungi and bacteria that were related, mainly, to a progressive decrease in the concentration of fatty acid methyl esters and the concentration of alkenes in the emissions; and to an increase of odorous compounds, mainly aldehydes, ketones and carboxylic acids, which were responsible for the unpleasant odors of waste. No significant differences were observed between the evolution of orujo characteristics compared to those of alperujo.

Salivary epidermal growth factor correlates with hospitalization length in rotavirus infection.

BACKGROUND: The IFI27 interferon gene expression has been found to be largely increased in rotavirus (RV)-infected patients. IFI27 gene encodes for a protein of unknown function, very recently linked to epidermal proliferation and related to the epidermal growth factor (EGF) protein. The EGF is a low-molecular-weight polypeptide that is mainly produced by submandibular and parotid glands, and it plays an important physiological role in the maintenance of oro-esophageal and gastric tissue integrity. Our aim was to determine salivary EGF levels in RV-infected patients in order to establish its potential relationship with IFI27 increased expression and EGF-mediated mucosal protection in RV infection. METHODS: We conducted a prospective comparative study using saliva samples from 27 infants infected with RV (sampled at recruitment during hospital admission and at convalescence, i.e. at least 3 months after recovery) and from 36 healthy control children. RESULTS: Median (SD) EGF salivary concentration was 777 (529) pg/ml in RV-infected group at acute phase and 356 (242) pg/m at convalescence, while it was 337 (119) pg/ml in the healthy control group. A significant association was found between EGF levels and hospitalization length of stay (P-value = 0.022; r2 = -0.63). CONCLUSIONS: The salivary levels of EGF are significantly increased during the acute phase of natural RV infection, and relate to length of hospitalization. Further assessment of this non-invasive biomarker in RV disease is warranted.

Prediction of 67Ga production using the Monte Carlo code MCNPX.

The widely used Monte Carlo simulation code Monte Carlo N-Particle System (MCNPX) has been utilized to simulate the production of (67)Gallium via multiple nuclear reaction channels. Based on the MCNPX-generated, energy-dependent proton flux within a Zn target during irradiation, the (67)Ga production yield was determined. Theoretical calculations of the production yield using the stopping power from the SRIM (stopping and range of ions in matter) code were compared to the measurements from the MCNPX code. These results were in good agreement with reported data, thus confirming the usefulness and accuracy of MCNPX as a tool for the design and optimization of targets for the production of other radionuclides.

Expression and function of the insulin receptor in normal and osteoarthritic human chondrocytes: modulation of anabolic gene expression, glucose transport and GLUT-1 content by insulin.

OBJECTIVE: Chondrocytes respond to insulin, but the presence and role of the specific high affinity insulin receptor (InsR) has never been demonstrated. This study determined whether human chondrocytes express the InsR and compared its abundance and function in normal and osteoarthritis (OA) human chondrocytes. DESIGN: Cartilage sections were immunostained for detection of the InsR. Non-proliferating chondrocyte cultures from normal and OA human cartilage were treated with 1nM or 10nM insulin for various periods. InsR, insulin-like growth factor receptor (IGFR), aggrecan and collagen II mRNA levels were assessed by real time RT-PCR. InsR, glucose transporter (GLUT)-1, phospho-InsRbeta and phospho-Akt were evaluated by western blot and immunofluorescence. Glucose transport was measured as the uptake of [3H]-2-Deoxy-d-Glucose (2-DG). RESULTS: Chondrocytes staining positively for the InsR were scattered throughout the articular cartilage. The mRNA and protein levels of the InsR in OA chondrocytes were approximately 33% and 45%, respectively, of those found in normal chondrocytes. Insulin induced the phosphorylation of the InsRbeta subunit. Akt phosphorylation and 2-DG uptake increased more intensely in normal than OA chondrocytes. Collagen II mRNA expression increased similarly in normal and OA chondrocytes while aggrecan expression remained unchanged. The Phosphoinositol-3 Kinase (PI3K)/Akt pathway was required for both basal and insulin-induced collagen II expression. CONCLUSIONS: Human chondrocytes express functional InsR that respond to physiologic insulin concentrations. The InsR seems to be more abundant in normal than in OA chondrocytes, but these still respond to physiologic insulin concentrations, although some responses are impaired while others appear fully activated. Understanding the mechanisms that regulate the expression and function of the InsR in normal and OA chondrocytes can disclose new targets for the development of innovative therapies for OA.

Epidemiología de las fisuras labiales y palatinas durante los años 1990–2004 en Asturias / The epidemiology of cleft lip and palate over the period 1990–2004 in Asturias

Introducción: Las fisuras labiales y palatinas son los defectos congénitos faciales más frecuentes. Objetivo: Conocer la frecuencia de estos defectos en Asturias y realizar una descripción clinicoepidemiológica de sus anomalías asociadas. Metodología: Análisis de los datos del Registro de Defectos Congénitos de Asturias de los años 1990–2004 sobre una población de 103.452 nacidos y comparación con el European Concerted Action on Congenital Anomalies and Twins y otros registros españoles. Resultados: De los 145 casos registrados, el 26,9% eran fisuras labiales, el 28,3% eran fisuras labiopalatinas y el 44,8% eran fisuras palatinas. La prevalencia total de las fisuras labiales o palatinas fue de 14,4 por 10.000 nacidos. Un 18,6% tenía otros defectos asociados, y fueron más frecuentes las anomalías esqueléticas, las cardiovasculares y las del sistema nervioso central. Un 22,1% de las fisuras labiales y palatinas pertenecía a un síndrome o secuencia reconocida. El diagnóstico prenatal fue del 12,4%, principalmente en los casos polimalformados y síndromes. Conclusiones: La prevalencia total de las fisuras labiales y palatinas en Asturias durante este período fue similar a la de otros registros europeos. Debido a la elevada asociación a otras anomalías, debe realizarse una búsqueda minuciosa de ellas, tanto en la ecografía prenatal como en la exploración del recién nacido (AU)

Introduction: Cleft lip and palate (oral clefts) are the most common congenital facial defects. Objective: To assess the prevalence of oral clefts and to describe the associated malformations in a geographically defined population. Method: Data from the Asturias Registry of Congenital Defects were used to investigate the epidemiology of congenital facial clefts over the period 1990–2004 among the 103,452 births in the region. The results were also compared with data from EUROCAT and other Spanish registries. Results: Out of 145 oral clefts recorded, cleft lip was 26.9%, cleft lip and palate 28.3% and cleft palate 44.8%. Total prevalence of oral clefts was 14.4 per 10,000 births. Other associated defects were found in 18.6% of the total cases, with skeletal, cardiovascular and central nervous systems being the most common anomalies. Syndromes or sequences were found in 22% of clefts. A prenatal diagnosis was made in 12.4%. Conclusion: The prevalence of oral clefts in Asturias over this period fell within the range reported for other European registries. An exhaustive prenatal ultrasound and examination of the affected newborns to look for other malformations should be considered in infants with clefts, due to the high association with them (AU)

Frecuencia y presentación clínica de los defectos oculares congénitos en Asturias (1990–2004) / Frequency and clinical presentation of congenital ocular anomalies in Asturias 1990–2004

Introducción: Los defectos oculares congénitos (DOC) pueden originar importante discapacidad. Objetivo: El objetivo de este estudio fue conocer la prevalencia total de los DOC en Asturias, su tendencia y realizar una descripción de su forma de presentación. Metodología: Análisis de los datos del Registro de Defectos Congénitos de Asturias (RDCA) de los años 1990–2004. La población estudiada fueron los 103.452 nacidos de madres residentes en Asturias en este periodo. Se calcularon las tasas de prevalencia total. Resultados: De los 3.035 casos con defectos congénitos registrados durante los 15 años estudiados, 70 tenían un DOC. La prevalencia total media fue de 6,8 por 10.000 nacidos, con una tendencia estable. Los más frecuentes fueron: las cataratas congénitas (2,0 por 10.000 nacidos vivos), la anoftalmia/microftalmia (1,4 por 10.000 nacidos vivos) y los colobomas (1,3 por 10.000 nacidos vivos). El 40 % de los DOC se presentaron de forma aislada, 37% pertenecían a un síndrome y 23% se asociaban a otras anomalías congénitas no sindrómicas. Conclusiones: La prevalencia total de los DOC durante este periodo en Asturias fue estable siendo las cataratas congénitas el DOC más frecuente. Más de la mitad de los DOC, en especial la anoftalmia/microftalmia se asociaron a otras malformaciones congénitas (AU)

Introduction: Congenital ocular anomalies (COAs) can produce serious disability. Objective: The purpose of this investigation was to assess the prevalence of COAs, their trends and to describe the associated malformations and syndromes in a geographically defined population. Method: Data from the Asturias Registry of Congenital Defects were used. The period studied was from 1990 to 2004 and the study population the 103,452 births of mothers living in the region. Total prevalence was calculated. Results: A total of 3035 cases with congenital defects were recorded, of these 70 had COAs. The total prevalence was 6.8 per 10000 births, with a stable trend during this period. The most common COAs were: congenital cataract (2.0 per 10000 births), anophthalmos/microphthalmos (1.4 per 10000 births) and coloboma (1.3 per 10000 births). 40% of COAs occurred as isolated defects, 37% were syndromes and 23% were associated with other congenital defects. Conclusions: The prevalence of COAs in Asturias over this period had a stable trend and the congenital cataract was the commonest COAs. COAs, particularly the anophthalmos/microphthalmos were associated with other congenital anomalies (AU)

[Frequency and clinical presentation of congenital ocular anomalies in Asturias 1990-2004]. / Frecuencia y presentación clínica de los defectos oculares congénitos en Asturias (1990-2004).

INTRODUCTION: Congenital ocular anomalies (COAs) can produce serious disability. OBJECTIVE: The purpose of this investigation was to assess the prevalence of COAs, their trends and to describe the associated malformations and syndromes in a geographically defined population. METHOD: Data from the Asturias Registry of Congenital Defects were used. The period studied was from 1990 to 2004 and the study population the 103,452 births of mothers living in the region. Total prevalence was calculated. RESULTS: A total of 3035 cases with congenital defects were recorded, of these 70 had COAs. The total prevalence was 6.8 per 10000 births, with a stable trend during this period. The most common COAs were: congenital cataract (2.0 per 10000 births), anophthalmos/microphthalmos (1.4 per 10000 births) and coloboma (1.3 per 10000 births). 40% of COAs occurred as isolated defects, 37% were syndromes and 23% were associated with other congenital defects. CONCLUSIONS: The prevalence of COAs in Asturias over this period had a stable trend and the congenital cataract was the commonest COAs. COAs, particularly the anophthalmos/microphthalmos were associated with other congenital anomalies.

[The epidemiology of cleft lip and palate over the period 1990-2004 in Asturias]. / Epidemiología de las fisuras labiales y palatinas durante los años 1990-2004 en Asturias.

INTRODUCTION: Cleft lip and palate (oral clefts) are the most common congenital facial defects. OBJECTIVE: To assess the prevalence of oral clefts and to describe the associated malformations in a geographically defined population. METHOD: Data from the Asturias Registry of Congenital Defects were used to investigate the epidemiology of congenital facial clefts over the period 1990-2004 among the 103,452 births in the region. The results were also compared with data from EUROCAT and other Spanish registries. RESULTS: Out of 145 oral clefts recorded, cleft lip was 26.9%, cleft lip and palate 28.3% and cleft palate 44.8%. Total prevalence of oral clefts was 14.4 per 10,000 births. Other associated defects were found in 18.6% of the total cases, with skeletal, cardiovascular and central nervous systems being the the most common anomalies. Syndromes or sequences were found in 22% of clefts. A prenatal diagnosis was made in 12.4%. CONCLUSION: The prevalence of oral clefts in Asturias over this period fell within the range reported for other European registries. An exhaustive prenatal ultrasound and examination of the affected newborns to look for other malformations should be considered in infants with clefts, due to the high association with them.

Epidemiología de las cardiopatías congénitas en Asturias durante el período 1990–2004 / The epidemiology of congenital heart disease in Asturias (Spain) during the period 1990–2004

Introducción: Las cardiopatías congénitas (CC) son los defectos congénitos (DC) más comunes. Objetivo: Conocer la prevalencia total de las CC en Asturias y su tendencia y realizar una descripción de las anomalías asociadas y los síndromes o las secuencias. Material y métodos: Análisis de los datos del Registro de DC de Asturias de los años 1990–2004. La población estudio fueron los 103.452 nacidos de madres residentes en Asturias en ese período. Se calcularon las tasas de prevalencia total y al nacimiento. Resultados: De los 3.035 casos con DC registrados durante los 15 años estudiados, 778 tenían una CC. La prevalencia total media fue de 75,2 por 10.000 nacidos, con una tendencia ascendente. Las más frecuentes fueron la comunicación interventricular (28,8 por cada 10.000 nacidos vivos), los defectos del septo auricular (10,3 por cada 10.000 nacidos vivos) y la persistencia del ductus arterioso (6,0 por cada 10.000 nacidos vivos). El 73,6% de las CC se presentó de forma aislada, el 12,5% asociadas a otras anomalías congénitas y el 14% pertenecía a un síndrome o a una secuencia. El diagnóstico prenatal fue del 7,3% (del 3,8% en los casos aislados). Conclusiones: La prevalencia total de las CC en Asturias durante este período fue similar a la de otros registros europeos. El aparente incremento de la prevalencia se debió a un mayor diagnóstico de los defectos menores, mientras que las CC más graves mantuvieron una frecuencia estable. El diagnóstico prenatal de las CC en Asturias fue inferior al de otros registros europeos (AU)

Introduction: Congenital heart diseases (CHDs) are the most common type of birth defect. Objective: The purpose of this investigation was to assess the prevalence and trends of CHDs, and to describe the associated malformations and syndromes or sequences in a geographically defined population. Material and methods: Data wers collected from the Asturias Registry of Congenital Defects. The period studied was from 1990 to 2004, and the study population was the 103,452 births of mothers living in the region. Total prevalence and birth prevalence were calculated. Results: A total of 3035 cases with congenital defects were recorded, of these 778 had CHDs. The total prevalence was 75.2 per 10000 births, with an upward trend during this period. The most common CHDs were: ventricular septal defects (28.8 per 10000 births), atrial septal defects (10.3 per 10000 births) and patent ductus arteriosus (6.0 per 10000 births). A total of 73.6% of CHDs occurred as isolated defects, 12.5% with other congenital defects and 14% were syndromes or sequences. Prenatal diagnosis was effective in only 7.3% (3.8% in isolated cases). Conclusions: The prevalence of CHDs in Asturias over this period falls within the range reported for other European registries. The apparent increase in prevalence of CHD results mainly from improved diagnosis of minor defects, but there has been no change over time in birth prevalence of more serious defects (AU)

[The epidemiology of congenital heart disease in Asturias (Spain) during the period 1990-2004]. / Epidemiología de las cardiopatías congénitas en Asturias durante el período 1990-2004.

INTRODUCTION: Congenital heart diseases (CHDs) are the most common type of birth defect. OBJECTIVE: The purpose of this investigation was to assess the prevalence and trends of CHDs, and to describe the associated malformations and syndromes or sequences in a geographically defined population. MATERIAL AND METHODS: Data were collected from the Asturias Registry of Congenital Defects. The period studied was from 1990 to 2004, and the study population was the 103,452 births of mothers living in the region. Total prevalence and birth prevalence were calculated. RESULTS: A total of 3035 cases with congenital defects were recorded, of these 778 had CHDs. The total prevalence was 75.2 per 10,000 births, with an upward trend during this period. The most common CHDs were: ventricular septal defects (28.8 per 10,000 births), atrial septal defects (10.3 per 10,000 births) and patent ductus arteriosus (6.0 per 10,000 births). A total of 73.6% of CHDs occurred as isolated defects, 12.5% with other congenital defects and 14% were syndromes or sequences. Prenatal diagnosis was effective in only 7.3% (3.8% in isolated cases). CONCLUSIONS: The prevalence of CHDs in Asturias over this period falls within the range reported for other European registries. The apparent increase in prevalence of CHD results mainly from improved diagnosis of minor defects, but there has been no change over time in birth prevalence of more serious defects.

Evolución del diagnóstico prenatal delas anomalías cromosómicas en Asturias(España). Período 1990-2004 / Prenatal diagnosis trend for chromosomal abnormalities in Asturias (Spain). Period 1990-2004

Fundamento. Evaluar el impacto del diagnóstico prenatal(DP) en las anomalías cromosómicas (AC).Métodos. Durante 15 años (1990-2004) el Registro deDefectos Congénitos de Asturias (RDCA) recogió informaciónsobre AC. El RDCA es un registro de base poblacionalque incluye todos los diagnósticos ya sean abortos, mortinatos,o nacidos vivos hasta los 5 años de edad. Se analizaronlos datos de las AC, particularmente del síndrome deDown, síndrome de Turner, y trisomía 18, y la evolución delDP.Resultados. Se diagnosticaron 356 AC, aumentando elDP con el paso de los años, más en el grupo correspondientea mujeres de 35 años y más (30 % en menores de 35 años entre1990 y 1993, frente a 50 % entre 2002 y 2004; 48 % enmujeres de 35 años y más en el primer período frente a 83%en el segundo). En el síndrome de Down en las mujeres menoresde 35 años entre 2002 y 2004 el DP apenas alcanzó el30 %. En la trisomía 18 y en el síndrome de Turner, el porcentajede DP fue alto, debido principalmente a hallazgosecográficos.Conclusiones. El DP de las AC ha mejorado sus resultadosa lo largo de los 15 años, con una mejoría significativaen el diagnóstico ecográfico, excepto en el síndrome deDown en el grupo de menores de 35 años (AU)

Methods. Over 15 years (1990-2004) the Registro deDefectos Congénitos de Asturias (RDCA) collected informationon CA. The RDCA is a population-based registrythat includes all diagnosed cases whether abortions, stillbirths,or live birth until the age of five. The data obtainedwere analyzed for the CA, particularly for Downsyndrome, Turner syndrome and trisomy 18, and the evolutionof PD.Results. 356 chromosomal abnormalities were diagnosed,the PD increased over the years, especially in womenaged 35 and over (30% under the age of 35 between 1990and 1993, compared with 50% between 2002 and 2004;48% in women aged 35 and over in the first period comparedto 83% in the second). In Down syndrome data in thegroup of women under 35 years in 2002-2004 PD barelyreached 30%. In trisomy 18 and Turner syndrome, the averageof PD was high, mainly due to ultrasound findings.Conclusions. PD on CA has improved its results over15 years, with a significant improvement in the ultrasounddiagnosis, except for Down syndrome in the groupof women under 35 years (AU)

Evolución del diagnóstico prenatal de los defectos congénitos estructurales en Asturias. Período 1990-2004 / Prenatal diagnosis trend for structural birth defects in Asturias (Spain). Period 1990-2004

Fundamento. Evaluar el impacto del diagnóstico prenatal(DP) en los defectos congénitos estructurales (DCE).Métodos. Durante 15 años (1990-2004) el Registro deDefectos Congénitos de Asturias (RDCA) recogió informaciónsobre defectos congénitos (DC). El RDCA es un registrode base poblacional que incluye todos los diagnósticos yasean abortos, mortinatos, o nacidos vivos hasta los cincoaños de edad. Se analizaron datos obtenidos de los defectosde cierre del tubo neural (DTN), hernia diafragmática (HD),onfalocele, gastrosquisis, y cardiopatías congénitas, y la evolucióndel DP de estos defectos.Resultados. Se diagnosticaron un total de 3.035 DC(2,9 % sobre el total de nacimientos), siendo 560 los diagnósticosprenatales (18,5 %). Se registraron 126 casos deDTN con un porcentaje de DP igual o superior al 90 % en losperíodos estudiados, principalmente a expensas del diagnósticoecográfico. Hubo 45 casos de HD, con un incrementosustancial en el DP (68 % en los últimos años). En elcaso del onfalocele y la gastrosquisis, también se produjouna mejoría en la frecuencia del DP, especialmente en elcaso de las gastrosquisis, siendo diagnosticadas el 90%prenatalmente. El 10,6 % de las cardiopatías congénitas sediagnosticaron antes de nacer, y analizando las ocho másseveras y estructuralmente más complejas el DP apenas llegaal 20 % (AU)

Objective. To asses the impact of prenatal diagnosis(PD) on structural birth defects.Methods. Over 15 years (1990-2004) the Registro deDefectos Congénitos de Asturias (RDCA) collected informationon birth defects (BD). The RDCA is a populationbasedregistry that includes all diagnosed cases whetherabortions, stillbirths, or live birth until the age of five.Data obtained were analyzed for the defects of the neuraltube closure (DNT), diaphragmatic hernia (DH), omphalocele,gastroschisis, and congenital heart disease, and theevolution of PD in these defects.Results. 3,035 BD were diagnosed (2.9% of totalbirths), of which 560 were prenatally (18.5%). They wererecorded 126 cases of DNT with an average of PD equalto or exceeds 90% in the periods studied, mainly due toultrasound diagnosis. There were 45 cases of DH, with asubstantial increase in the PD (68% the last years). Omphaloceleand gastroschisis, also show an increase in thefrequency of PD, especially in gastroschisis, being diagnosedthe 90% of them prenatally. 10.6% of congenitalheart diseases were diagnosed prenatally, and the eightvalues harsher and more structurally complex PD barelyreaches 20% (AU)

Thick tellurium electrodeposition on nickel-coated copper substrate for 124I production.

Tellurium electrodeposition on a nickel-coated copper substrate was investigated for production of iodine-124. The electrodeposition experiments were carried out by the alkali plating baths. The optimum conditions of the electrodeposition of tellurium were as follows: 6 g l(-1) tellurium, pH=10, DC current density of ca. 8.55 mA cm(-2) and room temperature.

Universal and nonuniversal features in a model of city traffic.

The complex behavior that occurs when traffic lights are synchronized is studied. Two strategies are considered: all lights in phase, and a "green wave" with a propagating green signal. It is found that traffic variables such as traveling time, velocity, and fuel consumption, near resonance, follow critical scaling laws. For the green wave, it is shown that time and velocity scaling laws hold even for random separation between traffic lights. These results suggest the concept of transient resonances, which can be induced by adaptively changing the phase of traffic lights. This may be important to consider when designing strategies for traffic control in cities, where short trajectories, and thus transient solutions, are likely to be relevant.

Estradiol sustained release from high affinity cyclodextrin hydrogels.

Hydrogels for loading estradiol and controlling its release were prepared cross-linking various cyclodextrins with ethyleneglycol diglycidylether. To select the more adequate cyclodextrins, estradiol solubility diagrams in water with beta-cyclodextrin (betaCD), methyl-beta-cyclodextrin (MbetaCD), hydroxypropyl-beta-cyclodextrin (HPbetaCD), and sulfobutyl-beta-cyclodextrin (SBbetaCD) were made in absence and presence of hydroxypropyl methylcellulose (HPMC) applying or not autoclaving. Although all cyclodextrins showed enough complexation capability, the low solubility of betaCD and the high anionic character of SBbetaCD hindered the cross-linking process, and these cyclodextrins were discarded for preparing hydrogels. Hydrogels prepared with MbetaCD (20%, 25%) or HPbetaCD (20%, 25%, and 30%), with or without HPMC 0.25%, absorbed 4-10 times their weight in water and loaded up to 24 mg estradiol per gram, which is 500 times greater than the amount of drug that can be dissolved in their aqueous phase. Positive linear correlation was found between the stability constant and the network/water partition coefficients of drug. The hydrogels sustained the release up to one week; the affinity of estradiol for the cyclodextrin units controlling the process, as shown by the negative correlation with the release rate constants. These results highlight the potential of cyclodextrin complexation for the development of hydrogels useful in loading hydrophobic drugs and controlling their release.

Drug solubilization and delivery from cyclodextrin-Pluronic aggregates.

Colloidal systems based on Pluronic F127 (PF127) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) have been characterized with a view to their potential use as delivery systems of hydrophobic drugs. Complexation of PF127 and HPbetaCD was evaluated by surface tension measurements, 1H-NMR spectroscopy and transmission electron microscopy. The critical micellar concentration, CMC, at 25 degrees C of PF127 (0.39 mM in pH 5.8 and 7.4 phosphate buffers, and 0.59 mM in pH 4.5 acetic/acetate and lactic/lactate buffers) was shifted to higher values by the addition of 38.17 mM HPbetaCD (CMC(app) = 1.18 mM). This is related to the threading of HPbetaCD onto the PF127 chains, as confirmed by 1H NMR experiments. HPbetaCD at this concentration notably raised the sol-gel transition temperature; the minimum PF127 concentration required for providing gelling systems in physiological environments being 13.4 mM. Both HPbetaCD and PF127 by themselves are able to notably increase the solubility of sertaconazole (SN). At HPbetaCD concentrations below 80 mM, an additive effect of both components on SN solubility was observed. At greater HPbetaCD concentrations, a non-additive increase occurred, which is related to the complexation of some PF127 unimers with HPbetaCD molecules, decreasing the total number of micelles and HPbetaCD cavities available for interacting with SN. The 13.4 mM PF127/38.17 mM HPbetaCD system, able to increase up to 100 times the SN solubility in pH5.8 phosphate buffer, showed temperature-dependent drug diffusion coefficients, able to control the release for one week at 37 degrees C.

Modeling traffic through a sequence of traffic lights.

We introduce a microscopic traffic model, based on kinematic behavior, which consists of a single vehicle traveling through a sequence of traffic lights that turn on and off with a specific frequency. The reconstructed function that maps the state of the vehicle from light to light displays complex behavior for certain conditions. This chaotic behavior, which arises by the discontinuous nature of the map, displays an essential ingredient in traffic patterns and could be of relevance in studying traffic situations.

[Limb reduction defects in Asturias (1986-1997): prevalence and clinical presentation]. / Defectos de reducción de extremidades en Asturias, 1986-1997: prevalencia y presentación clínica.

AIM: To determine the prevalence and clinical presentation of limb reduction defects in Asturias (Spain). PATIENTS AND METHODS: Among the 92300 newborns, stillbirths and induced abortions for congenital defects surveyed by the Registry of Congenital Defects in Asturias (population-based registry) during 1986-1997, we studied the children with limb reduction defects. Frequency is expressed as total prevalence per 10000 births. RESULTS: Seventy-three children with limb reduction defects were identified, with a total prevalence of 8 per 10000 births (CI 6.2-9.8): upper limbs were affected in 65.7%, lower limbs in 23.3% and both upper and lower limbs were affected in 11%. Transverse terminal defects were present in 49.3%, and were intercalary in 16.4%, preaxial longitudinal in 8.2%, postaxial longitudinal in 9.6%, split hand/foot in 9.6% and multiple in 6.8%. Limb deficiencies were found in 52%; of these, 48% were associated with other congenital defects. Four had chromosomal anomalies and 20 were syndromes. 31% had low birth weight for their gestational age. Alcohol exposure during pregnancy was recorded in three mothers. CONCLUSIONS: A detailed study of limb reduction defects could lead to a better understanding of clinical presentation and to an etio-pathogenic diagnosis to control risk factors.

Defectos de reducción de extremidades en Asturias, 1986-1997: prevalencia y presentación clínica / Limb reduction defects in asturias (1986-1997): prevalence and clinical presentation

OBJETIVO: Conocer la prevalencia y forma de presentación clínica de los defectos por reducción de extremidades en la población asturiana. PACIENTES Y MÉTODOS: Estudio de niños con defectos de reducción de extremidades entre los 91.300 nacidos vivos, nacidos muertos mayores de 500 g y abortos inducidos por defectos congénitos, de mujeres residentes en Asturias, controlados por el Registro de Defectos Congénitos de Asturias (registro de base poblacional) en el período 1986-1997. La frecuencia se expresa como prevalencia total por 10.000 nacidos. RESULTADOS: Durante el período estudiado, se registraron 73 casos, siendo la prevalencia total de 8 por 10.000 (intervalo de confianza del 95 por ciento, 6,2-9,8). El 65,7 por ciento de las anomalías observadas afectaban a las extremidades superiores, el 23,3 por ciento a las inferiores y el 11 por ciento a ambas. El 49,3 por ciento presentaba un defecto terminal transverso, el 16,4 por ciento un defecto intercalar, el 8,2 por ciento longitudinal preaxial, el 9,6 por ciento longitudinal postaxial, el 9,6 por ciento mano o pie hendido, y en el 6,8 por ciento el defecto era múltiple. El 52 por ciento eran formas aisladas y el 48 por ciento se manifestaron como defecto asociado a otras malformaciones. En 4 existía alteración cromosómica, y en 20 la reducción de extremidades formaba parte de un síndrome, asociación o secuencia definida. El 31,5 por ciento presentaba bajo peso para la edad de gestación. En tres madres se constató ingestión importante de alcohol. CONCLUSIÓN: El estudio detallado de los defectos congénitos por reducción de extremidades permite un mejor conocimiento de sus formas clínicas de presentación, además de acercarnos a un diagnóstico etiopatogénico, con posibilidad de actuar sobre los factores de riesgo (AU)