Effects of DC Magnetic Fields on Magnetoliposomes.

The potential use of magnetic nanoparticles (MNPs) in biomedicine as magnetic resonance, drug delivery, imagenology, hyperthermia, biosensors, and biological separation has been studied in different laboratories. One of the challenges on MNP elaboration for biological applications is the size, biocompatibility, heat efficiency, stabilization in physiological conditions, and surface coating. Magnetoliposome (ML), a lipid bilayer of phospholipids encapsulating MNPs, is a system used to reduce toxicity. Encapsulated MNPs can be used as a potential drug and a gene delivery system, and in the presence of magnetic fields, MLs can be accumulated in a target tissue by a strong gradient magnetic field. Here, we present a study of the effects of DC magnetic fields on encapsulated MNPs inside liposomes. Despite their widespread applications in biotechnology and environmental, biomedical, and materials science, the effects of magnetic fields on MLs are unclear. We use a modified coprecipitation method to synthesize superparamagnetic nanoparticles (SNPs) in aqueous solutions. The SNPs are encapsulated inside phospholipid liposomes to study the interaction between phospholipids and SNPs. Material characterization of SNPs reveals round-shaped nanoparticles with an average size of 12 nm, mainly magnetite. MLs were prepared by the rehydration method. After formation, we found two types of MLs: one type is tense with SNPs encapsulated and the other is a floppy vesicle that does not show the presence of SNPs. To study the response of MLs to an applied DC magnetic field, we used a homemade chamber. Digitalized images show encapsulated SNPs assembled in chain formation when a DC magnetic field is applied. When the magnetic field is switched off, it completely disperses SNPs. Floppy MLs deform along the direction of the external applied magnetic field. Solving the relevant magnetostatic equations, we present a theoretical model to explain the ML deformations by analyzing the forces exerted by the magnetic field over the surface of the spheroidal liposome. Tangential magnetic forces acting on the ML surface result in a press force deforming MLs. The type of deformations will depend on the magnetic properties of the mediums inside and outside the MLs. The model predicts a coexistence region of oblate-prolate deformation in the zone where χ = 1. We can understand the chain formation in terms of a dipole-dipole interaction of SNP.

On a fundamental description of the Kovacs' kinetic signatures in glass-forming systems.

The time-evolution equation for the time-dependent static structure factor of the non-equilibrium self-consistent generalized Langevin equation (NE-SCGLE) theory was used to investigate the kinetics of glass-forming systems under isochoric conditions. The kinetics are studied within the framework of the fictive temperature (TF) of the glassy structure. We solve for the kinetics of TF(t) and the time-dependent structure factor and find that they are different but closely related by a function that depends only on temperature. Furthermore, we are able to solve for the evolution of TF(t) in a set of temperature-jump histories referred to as the Kovacs' signatures. We demonstrate that the NE-SCGLE theory reproduces all the Kovacs' signatures, namely, intrinsic isotherm, asymmetry of approach, and memory effect. In addition, we extend the theory into largely unexplored, deep glassy state, regions that are below the notionally "ideal" glass temperature.

First-principles prediction of multiple stationary states in glass-forming liquids.

In the present work, the Non-Equilibrium Self-Consistent Generalized Langevin Equation (NESCGLE) theory is used to predict the final state of glass-forming liquids subjected to different cooling processes. We show that the NESCGLE theory correctly describes two essential features of the glass transition. Such features are the structural recovery and the dependence of the final state with the cooling rate. We demonstrate that below a particular temperature Tc, the system is unable to equilibrate, independently of the cooling rate. We show that the equilibrium state is only reached for the quasistatic process. Additionally, we show how, from the NESCGLE theory, it is possible to deduce a relaxation model of structural recovery, for which we obtain molecular expressions of the parameters.

Resiniferatoxin modulates the Th1 immune response and protects the host during intestinal nematode infection.

In the early stage of the intestinal phase of Trichinella spiralis infection, the host triggers a Th1-type immune response with the aim of eliminating the parasite. However, this response damages the host which favours the survival of the parasite. In the search for novel pharmacological strategies that inhibit the Th1 immune response and assist the host against T. spiralis infection, a recent study showed that resiniferatoxin had anti-inflammatory activity contributed to the host in T. spiralis infection. In this study, we evaluated whether RTX modulates the host immune response through the inhibition of Th1 cytokines in the intestinal phase. In addition, it was determined whether the treatment with RTX affects the infectivity of T. spiralis-L1 and the development of the T. spiralis life cycle. Our results show that RTX decreased serum levels of IL-12, INF-γ, IL-1ß, TNF-α and parasite burden on muscle tissue. It was observed that T. spiralis-L1 treated with RTX decreased their infectivity affecting the development of the T. spiralis life cycle in mouse. These results demonstrate that RTX is able to inhibit the production of Th1 cytokines, contributing to the defence against T. spiralis, which places it as a potential drug modulator of the immune response.

Resiniferatoxin lowers TNF-α, NO and PGE2 in the intestinal phase and the parasite burden in the muscular phase of Trichinella spiralis infection.

During the course of infection with Trichinella spiralis, an inflammatory response is triggered at the intestinal level in the host, playing a crucial role in the expulsion and elimination of the parasite. However, several studies have demonstrated that this inflammatory response is harmful to the host; hence, the importance of studying molecules with therapeutic potential like resiniferatoxin, which is known to have an anti-inflammatory effect both in vitro and in vivo. In this article, we evaluated the anti-inflammatory activity of resiniferatoxin during the intestinal phase of T. spiralis infection by quantitatively determining the levels of TNF-α, NO and PGE2 as well as the percentage of eosinophils in the blood and intestinal pathology. In addition, parasite burden was determined during the muscle infection. Our results show that resiniferatoxin lowered the serum levels of TNF-α, NO and PGE2 , as well as the percentage of eosinophils in the blood and intestinal pathology during the intestinal infection. Moreover, resiniferatoxin also lowered the parasite burden in muscle, resulting in a reduction of the humoral response (IgG) associated to treatment with resiniferatoxin. These findings suggest a potential therapeutic use of the anti-inflammatory effect of resiniferatoxin, which also contributes to host defence against the challenge of T. spiralis infection.

KIR Genes and Patterns Given by the A Priori Algorithm: Immunity for Haematological Malignancies.

Killer-cell immunoglobulin-like receptors (KIRs) are membrane proteins expressed by cells of innate and adaptive immunity. The KIR system consists of 17 genes and 614 alleles arranged into different haplotypes. KIR genes modulate susceptibility to haematological malignancies, viral infections, and autoimmune diseases. Molecular epidemiology studies rely on traditional statistical methods to identify associations between KIR genes and disease. We have previously described our results by applying support vector machines to identify associations between KIR genes and disease. However, rules specifying which haplotypes are associated with greater susceptibility to malignancies are lacking. Here we present the results of our investigation into the rules governing haematological malignancy susceptibility. We have studied the different haplotypic combinations of 17 KIR genes in 300 healthy individuals and 43 patients with haematological malignancies (25 with leukaemia and 18 with lymphomas). We compare two machine learning algorithms against traditional statistical analysis and show that the "a priori" algorithm is capable of discovering patterns unrevealed by previous algorithms and statistical approaches.

Evaluación de Termografía Tisular Diferenciada en Mama como Potencial Técnica para Asistir la Detección de Cáncer / Evaluation of Thermography Differentiated in Breast Tissue as Potential Technique to Assist Cancer Detection

Diversos grupos han propuesto el procesamiento de imágenes termográficas para detección de Cáncer de Mama (CaMa). Angiogénesis y vascularización dependientes del ciclo menstrual, edad e Índice de Masa Corporal (IMC) modifican la temperatura absoluta en la superficie tisular sin estar necesariamente asociadas a malignidad, en éste estudio proponemos la Termografía Tisular Diferenciada (TTD) en mama con respecto a su contralateral en espejo con el fin de observar diferencias térmicas características de malignidad. El presente trabajo evalúa la posibilidad de emplear la TTD como potencial técnica para asistir la detección de CaMa. Se muestrearon 110 mujeres voluntarias entre 40 y 60 años de edad segmentadas en dos grupos experimentales: grupo sanas (n=90) y grupo con CaMa (n=20) previamente diagnosticadas por mastografía e histopatología. Imágenes termográficas de ambas mamas fueron adquiridas con una cámara infrarroja y se estimó la TTD en relación a la mama contralateral de la misma paciente, se realizó un análisis de sensibilidad y especificidad y se comparó con el diagnóstico radiológico a través de curvas ROC tomando como referencia el diagnóstico histopatológico. La TTD en mama mostró rangos dinámicos diferenciables entre condiciones de malignidad respecto a benignidad. El análisis ROC mostró valores de sensibilidad y especificidad para el estimado TTD del 70% y 54% mientras que para el diagnóstico radiológico fue del 70% y 96%, respectivamente. La TTD muestra viabilidad técnica para asistir la detección de CaMa.

Several groups have proposed thermographic image processing for Breast Cancer (BC) detection. Angiogenesis and vascularization of menstrual cycle dependent, as well as age and Body Mass Index change the absolute temperature in the tissue surface without necessarily being associated with malignancy. We have proposed the Differentiated Tissue Thermography (DTT) in breast regarding its contralateral mirror in order to observe differences in temperature characteristics of malignancy. This study evaluates the possibility of using breast DTT as a potential technique to assist the detection of BC. We sampled 110 female volunteers between 40 and 60 years old segmented into two experimental groups: healthy group (n=90) and BC group (n=20), which were diagnosed by mammography and histopathology. Thermal images of both breasts were acquired with an infrared camera and the DTT was estimated relative to its contralateral breast in the same patient. A sensitivity and specificity analysis was developed and the DTT was compared with the radiological diagnosis by ROC curves with the histopathological report as reference. The DTT values showed distinguishable dynamic ranges between malignant and healthy conditions. ROC analysis showed sensitivity and specificity values for DTT of 70% and 54% while for the radiological diagnosis was 70% and 96% respectively. DTT showed technical viability to assist BC detection.

The shock and spall response of three industrially important hexagonal close-packed metals: magnesium, titanium and zirconium.

Magnesium, titanium and zirconium and their alloys are extensively used in industrial and military applications where they would be subjected to extreme environments of high stress and strain-rate loading. Their hexagonal close-packed (HCP) crystal lattice structures present interesting challenges for optimizing their mechanical response under such loading conditions. In this paper, we review how these materials respond to shock loading via plate-impact experiments. We also discuss the relationship between a heterogeneous and anisotropic microstructure, typical of HCP materials, and the directional dependency of the elastic limit and, in some cases, the strength prior to failure.

c-erbB-2 as a possible target for the use of magnetic nanoparticles in breast cancer cells.

Breast cancer (BC) is the most frequent malignancy among women worldwide and has been associated with high mortality because of the late treatment of the disease. Our group has proposed a selective ablation of breast cancer cells by the use of magnetic fields assisted by magnetic nanoparticles. The principle is to increase the conductivity of tumoral tissue by the use of a bioconjugated "nanoparticle-antibody" that recognizes specific antigens on the surface of the cancer cells. The aim of this study was to evaluate the c-erbB-2 antigen in breast cancer cells of type BT-474, MCF-7, and MDA-MB-231 as a possible target for the use of magnetic nanoparticles coupled to a specific Monoclonal Antibody (Mab). Quantitative real-time polymerase chain reaction and flow cytometry were used to estimate the relative expressions of the c-erbB-2 gene and the c-erbB-2 antigen in the cell lines, respectively. A covalent union of magnetic nanoparticles to anti c-erbB-2 Mab was used to develop the bioconjugate. Fluorescence microscopy was used to determine the cells that were tagged by the bioconjugate. The results show a well-differentiated relative expression of c-erbB-2 in the studied cell lines and are qualitatively in agreement with the fluorescent marking by the magnetic nanoparticles. The selected breast cancer cells appear to be suitable for experimental evaluation of selective targeting by magnetic nanoparticles.

The RNAi machinery regulates growth and development in the filamentous fungus Trichoderma atroviride.

The RNAi machinery is generally involved in genome protection in filamentous fungi; however, the physiological role of RNAi has been poorly studied in fungal models. Here, we report that in the filamentous fungus Trichoderma atroviride, the products of the dcr2 and rdr3 genes control reproductive development, because mutations in these genes affect conidiation. In addition, Dcr1 together with Dcr2 control vegetative growth since Δdcr1, Δdcr2 and Δdcr1Δdcr2 present morphological alterations. Whole-genome transcriptional analysis of WT, Δdcr1, Δdcr2 and Δdcr1Δdcr2 show that each Dicer controls different biological processes, such as development or metabolism, which could explain the lack of conidiation in the mutants. Finally, we observed sRNAs that are differentially expressed in the WT and Δdcr2. The expression of some of these sRNAs correlates with the expression of differential transcripts, suggesting that these mRNAs may contain the corresponding targets. Together these data show that in T. atroviride, the RNAi machinery plays a central role in endogenous processes such as development and fitness, beyond controlling genome protection against invasive nucleic acids as reported for other fungi.

Genome-wide association study of type 2 diabetes in a sample from Mexico City and a meta-analysis of a Mexican-American sample from Starr County, Texas.

AIMS/HYPOTHESIS: We report a genome-wide association study of type 2 diabetes in an admixed sample from Mexico City and describe the results of a meta-analysis of this study and another genome-wide scan in a Mexican-American sample from Starr County, TX, USA. The top signals observed in this meta-analysis were followed up in the Diabetes Genetics Replication and Meta-analysis Consortium (DIAGRAM) and DIAGRAM+ datasets. METHODS: We analysed 967 cases and 343 normoglycaemic controls. The samples were genotyped with the Affymetrix Genome-wide Human SNP array 5.0. Associations of genotyped and imputed markers with type 2 diabetes were tested using a missing data likelihood score test. A fixed-effects meta-analysis including 1,804 cases and 780 normoglycaemic controls was carried out by weighting the effect estimates by their inverse variances. RESULTS: In the meta-analysis of the two Hispanic studies, markers showing suggestive associations (p < 10(-5)) were identified in two known diabetes genes, HNF1A and KCNQ1, as well as in several additional regions. Meta-analysis of the two Hispanic studies and the recent DIAGRAM+ dataset identified genome-wide significant signals (p < 5 × 10(-8)) within or near the genes HNF1A and CDKN2A/CDKN2B, as well as suggestive associations in three additional regions, IGF2BP2, KCNQ1 and the previously unreported C14orf70. CONCLUSIONS/INTERPRETATION: We observed numerous regions with suggestive associations with type 2 diabetes. Some of these signals correspond to regions described in previous studies. However, many of these regions could not be replicated in the DIAGRAM datasets. It is critical to carry out additional studies in Hispanic and American Indian populations, which have a high prevalence of type 2 diabetes.

Diabetes and other glucose metabolism abnormalities in Mexican Zapotec and Mixe Indians.

AIMS: Aboriginal populations are experiencing an explosive rise in the prevalence of Type 2 diabetes. The purpose of this study was to estimate the prevalence of diabetes and other glucose metabolism abnormalities in Mexican Zapotec and Mixe Indians and to determine their association with known risk factors. METHODS: A cross-sectional study was conducted in the southern Mexican state of Oaxaca. Two communities of Zapotec population and three of Mixe population were randomly chosen. Mexican Indians>or=35 years old were invited to participate; 394 Zapotec and 730 Mixe Indians participated. Diabetes and other glucose metabolism abnormalities were diagnosed using standard World Health Organization criteria after an oral glucose tolerance test. Prevalence and odds ratio (OR) were estimated with 95% confidence intervals (95% CI). RESULTS: The crude prevalence of diabetes was 8.19% (95% CI 6.7-9.9%) and the age- and sex-adjusted prevalence was 8.27%, significantly higher among Zapotec (8.71%) than among Mixe Indians (6.90%). The prevalence of impaired glucose tolerance was 9.9% and 4.7% of the studied subjects had impaired fasting glucose. The main risk factors related to the occurrence of diabetes were a family history of diabetes (OR 4.1; 95% CI 1.9-8.8), obesity (OR 3.0; 95% CI 1.6-5.6), hypertension (OR 2.6; 95% CI 1.5-4.7) and a high-risk waist-hip ratio (4.6; 95% CI 1.2-17.7). CONCLUSIONS: The prevalence of diabetes is high in this population, the highest so far reported in Mexican Indians. Mexico's health system faces a huge challenge to avert the advanced spread of diabetes in this susceptible population.

The trianvil test apparatus: measurement of shear strength under pressure.

An experimental apparatus has been developed for performing shear tests on specimens held under moderately high hydrostatic pressures (up to the order of 10 GPa). This testing procedure experimentally determines the pressure dependent shear strength of thin foil specimens. This information is necessary for models of materials subjected to extreme pressures and can assist in model validation for models such as discrete dislocation dynamics simulations, among others. This paper reports the development of the experimental procedures and the results of initial experiments on thin foils of polycrystalline Ta performed under hydrostatic pressures ranging from 2 to 4 GPa. Subsequent characterization of the samples held under pressure established that the procedure described herein represents a reliable method to impose nearly uniform hydrostatic pressure on thin foil specimens. Both yielding and hardening behavior of Ta are observed to be sensitive to the imposed pressure.

High prevalence of diabetes and impaired fasting glucose in urban Latin America: the CARMELA Study.

AIMS: Cardiovascular risk is increased with glucose metabolism abnormalities. Prevalence data can support public health initiatives required to address this risk. The Cardiovascular Risk Factor Multiple Evaluation in Latin America (CARMELA) study was designed to estimate the prevalence of Type 2 diabetes, impaired fasting glucose and related risk factors in seven urban Latin American populations. METHODS: CARMELA was a cross-sectional, population-based study of 11 550 adults 25-64 years of age. With a multi-stage sample design of a probabilistic nature, approximately 1600 subjects were randomly selected in each city. RESULTS: Overall, the prevalence of diabetes was 7.0% (95% confidence intervals 6.5-7.6%). The prevalence of individuals with diabetes or impaired fasting glucose increased with increasing age. In the oldest age category, 55-64 years of age, prevalence of diabetes ranged from 9 to 22% and prevalence of impaired fasting glucose ranged from 3 to 6%. Only 16.3% of people with prior diagnosis of diabetes and who were receiving pharmacologic treatment, were in good glycaemic control (fasting glucose < 6.1 mmol/l). The prevalence of diabetes in individuals with abdominal obesity was approximately twofold higher. Participants with hypertension, elevated serum triglycerides and increased common carotid artery intima-media thickness were also more likely to have diabetes. CONCLUSIONS: The prevalence of diabetes and impaired fasting glucose is high in seven major Latin American cities; intervention is needed to avoid substantial medical and socio-economic consequences. CARMELA supports the associations of abdominal obesity, hypertension, elevated serum triglycerides and carotid intima-media thickness with diabetes.

Antinuclear antibodies: a marker associated with steroid dependence in patients with ulcerative colitis.

BACKGROUND: The autoimmune phenomena and the autoantibody profile have acquired great importance in ulcerative colitis (UC). Few studies have explored antinuclear antibodies (ANAs) prevalence, but not its association with steroid dependence. We hypothesized that ANAs could be a factor associated to steroid dependence. METHODS: Ninety-seven consecutive patients with UC were included. ANA titers and staining patterns were determined by indirect immunofluorescence. Gender, age, follow-up time, C-reactive protein (CRP), disease extent, Mayo Score Activity Index, extraintestinal manifestations, and steroid dependence were analyzed in univariate and multivariate models. RESULTS: Ninety-seven patients were included and 49 (50.5%) were females; mean age was 41.7 +/- 22.2 years. Positivity for ANAs was encountered in 52 (53.5%) patients, and none for anti-dsDNA. The prevalence of ANAs was higher in steroid-dependent than in nonsteroid-dependent patients (77.8% versus 48.1%, P = 0.020; odds ratio [OR] = 3.8, 95% confidence interval [CI] 1.1-12.5), and in those with uveitis (100% versus 51.1%; P = 0.040) or pyoderma gangrenosum (100% versus 51.6%; P = 0.078). No association was observed with gender, age, CRP, disease extent, and Mayo Score Activity Index. The multiple regression analysis model showed an association between steroid dependence and ANAs (P = 0.033, OR = 3.9, 95% CI 1.4-14.9). CONCLUSIONS: ANAs are associated with steroid dependence in UC patients. Further studies are required to determine the role of ANAs as serological markers for prediction of steroid dependence in order to perform early therapeutic interventions with biological agents.

Bioactivation of a cobalt alloy by coating with wollastonite during investment casting.

Cobalt alloy samples were bioactivated during investment casting. The cavities of the investment mold were previously coated with wollastonite. Additionally, before coating with wollastonite, some mold cavities were filled out with graphite rods to avoid a chemical reaction between the wollastonite powder and the investment material. Half of the cast samples were heat treated at 1220 degrees C for 1 h. To perform the in vitro bioactivity assessment, the cast and heat-treated samples were immersed in a simulated body fluid solution (SBF) for a period of 21 days. The surface of the samples before and after immersion in SBF was characterized by SEM, EDX, and XRD analyses. During the casting, particles of pseudowollastonite were embedded on the metallic surface. After immersion of the samples in SBF, a ceramic layer was formed on both the alloy obtained by using the investment mold and the alloy obtained by using the graphite-filled cavity. The ceramic layer was thicker on the alloy cast in the investment mold. The layer was identified as hydroxyapatite by XRD analysis, in all the cases. The heat-treated samples after immersion in SBF showed the formation of a thin homogeneous layer consisting of fine grains of apatite.

Effect of wollastonite ceramics and bioactive glass on the formation of a bonelike apatite layer on a cobalt base alloy.

A biomimetic method was used to promote a bioactive surface on a cobalt base alloy (ASTM F-75). The metallic substrates were alkali treated and some of the samples were subsequently heat treated. The treated samples were immersed in simulated body fluid (SBF) on granular particles of either bioactive glass or wollastonite. For comparative purposes, no bioactive system was used in some tests. Three different methods were used for the immersion of the samples in SBF: 1) 21 days in SBF, 2) 21 days in 1.5 SBF, and 3) 7 days in SBF followed by 14 days in 1.5 SBF (re-immersion method). A bonelike apatite layer was formed on all the samples placed on wollastonite and bioactive glass particles. The morphology of the apatite layer formed by using the re-immersion method and wollastonite closely resembled the existing bioactive systems. No apatite layer was observed on the samples treated without bioactive material and soaked for 21 days in SBF or 1.5 SBF, apart from the substrates treated by using the re-immersion method. The heat treatment delayed the apatite formation in all the cases studied.