Iron-saturated bovine lactoferrin: a promising chemopreventive agent for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a tumor with minimal chance of cure due to underlying liver diseases, late diagnosis, and inefficient treatments. Thus, HCC treatment warrants the development of additional strategies. Lactoferrin (Lf) is a mammalian multifunctional iron-binding glycoprotein of the innate immune response and can be found as either a native low iron form (native-Lf) or a high iron form (holo-Lf). Bovine Lf (bLf), which shares many functions with human Lf (hLf), is safe for humans and has several anticancer activities, including chemotherapy boost in cancer. We found endogenous hLf is downregulated in HCC tumors compared with normal liver, and decreased hLf levels in HCC tumors are associated with shorter survival of HCC patients. However, the chemoprotective effect of 100% iron saturated holo-bLf on experimental hepatocarcinogenesis has not yet been determined. We aimed to evaluate the chemopreventive effects of holo-bLf in different HCC models. Remarkably, a single dose (200 mg kg-1) of holo-bLf was effective in preventing early carcinogenic events in a diethylnitrosamine induced HCC in vivo model, such as necrosis, ROS production, and the surge of facultative liver stem cells, and eventually, holo-bLf reduced the number of preneoplastic lesions. For an established HCC model, holo-bLf treatment significantly reduced HepG2 tumor burden in xenotransplanted mice. Finally, holo-bLf in combination with sorafenib, the advanced HCC first-line treatment, synergistically decreased HepG2 viability by arresting cells in the G0/G1 phase of the cell cycle. Our findings provide the first evidence suggesting that holo-bLf has the potential to prevent HCC or to be used in combination with treatments for established HCC.

Risk factors associated with valvular calcification in patients with chronic kidney disease. Analysis of NEFRONA study.

INTRODUCTION: Patients with chronic kidney disease (CKD) are at high risk of cardiovascular morbidity and mortality. Subclinical cardiac structural alterations have prognostic value in these patients. The aim was to analyse the prevalence of valvular calcification, the evolution and the relationship with different risk factors. MATERIAL AND METHODS: Part of the sample of the NEFRONA study was randomly selected. Aortic and mitral valve calcification were analysed in echocardiograms performed at the baseline visit and at 24 months. RESULTS: We included 397 patients, the estimated basal glomerular filtrate (eGFR) was 33 ml/min with significant decrease to 30.9 ml/min. There was an increase in the area of carotid and femoral plaque, as well as an increase in patients with aortic and mitral calcification at 24 months. A positive association of mitral calcification at 24 months with age, ankle-brachial index (ABI) and calcium-phosphorus product (CaxP) at baseline visit was observed, without association with eGFR. Aortic calcification at 24 months was positively associated with age, phosphorous and total carotid plaque area at baseline, with no relationship to eGFR. CONCLUSIONS: A significant prevalence of valvular calcification was observed in patients with CKD without known cardiovascular disease.Two-year progression was observed independently of the eGFR. Patients with higher risk of mitral valve calcification were those with older age, higher ABI and CaxP product. Patients with a higher risk of aortic calcification were those with older age, higher phosphorous levels and larger area of carotid plaque. Identifying these higher risk patients would help to avoid future cardiovascular events intensifying follow-ups.

[Risk factors associated with valvular calcification in patients with chronic kidney disease. Analysis of NEFRONA Study]. / Factores de riesgo asociados a la calcificación valvular en pacientes con enfermedad renal crónica. Análisis del Estudio Nefrona.

INTRODUCTION: Patients with chronic kidney disease (CKD) are at high risk of cardiovascular morbidity and mortality. Subclinical cardiac structural alterations have prognostic value in these patients. The aim was to analyse the prevalence of valvular calcification, the evolution and the relationship with different risk factors. MATERIAL AND METHODS: Part of the sample of the NEFRONA study was randomly selected. Aortic and mitral valve calcification were analysed in echocardiograms performed at the baseline visit and at 24 months. RESULTS: We included 397 patients, the estimated basal glomerular filtrate (eGFR) was 33ml/min with significant decrease to 30.9ml/min. There was an increase in the area of carotid and femoral plaque, as well as an increase in patients with aortic and mitral calcification at 24 months. A positive association of mitral calcification at 24 months with age, ankle-brachial index (ABI) and calcium-phosphorus product (CaxP) at baseline visit was observed, without association with eGFR. Aortic calcification at 24 months was positively associated with age, phosphorous and total carotid plaque area at baseline, with no relationship to eGFR. CONCLUSIONS: A significant prevalence of valvular calcification was observed in patients with CKD without known cardiovascular disease.Two-year progression was observed independently of the eGFR. Patients with higher risk of mitral valve calcification were those with older age, higher ABI and CaxP product. Patients with a higher risk of aortic calcification were those with older age, higher phosphorous levels and larger area of carotid plaque. Identifying these higher risk patients would help to avoid future cardiovascular events intensifying follow-ups.

Exploring the Different Degrees of Magnetic Disorder in TbxR1-xCu2 Nanoparticle Alloys.

Recently, potential technological interest has been revealed for the production of magnetocaloric alloys using Rare-Earth intermetallics. In this work, three series of TbxR1-xCu2 (R ≡ Gd, La, Y) alloys have been produced in bulk and nanoparticle sizes via arc melting and high energy ball milling. Rietveld refinements of the X-ray and Neutron diffraction patterns indicate that the crystalline structure in all alloys is consistent with TbCu2 orthorhombic Imma bulk crystalline structure. The analyses of the DC-magnetisation (MDC) and AC-susceptibility (χAC) show that three distinct degrees of disorder have been achieved by the combination of both the Tb3+ replacement (dilution) and the nanoscaling. These disordered states are characterised by transitions which are evident to MDC, χAC and specific heat. There exists an evolution from the most ordered Superantiferromagnetic arrangement of the Tb0.5La0.5Cu2 NPs with Néel temperature, TN∼ 27 K, and freezing temperature, Tf∼ 7 K, to the less ordered weakly interacting Superparamagnetism of the Tb0.1Y0.9Cu2 nanoparticles (TN absent, and TB∼ 3 K). The Super Spin Glass Tb0.5Gd0.5Cu2 nanoparticles (TN absent, and Tf∼ 20 K) are considered an intermediate disposition in between those two extremes, according to their enhanced random-bond contribution to frustration.

Delaying surgery by more than 10 weeks after long-course neoadjuvant radiotherapy in locally advanced rectal cancer patients improves pathologic complete response.

BACKGROUND: We currently do not know the optimal time interval between the end of chemoradiotherapy and surgery. Longer intervals have been associated with a higher pathological response rate, worse pathological outcomes and more morbidity. The aim of this study was to evaluate the effect and safety of the current trend of increasing time interval between the end of chemoradiotherapy and surgery (< 10 weeks vs. ≥ 10 weeks) on postoperative morbidity and pathological outcomes. This study analyzed 232 consecutive patients with locally advanced rectal cancer treated with long-course neoadjuvant chemoradiotherapy from January 2012 to August 2018. 125 patients underwent surgery before 10 weeks from the end of chemoradiotherapy (Group 1) and 107 patients underwent surgery after 10 or more weeks after the end of chemoradiotherapy (Group 2). Results have shown that wait for ≥ 10 weeks did not compromise surgical safety. Pathological complete response and tumor stage was statistically significant among groups. The effect of wait for ≥ 10 weeks before surgery shown higher tumor regression than the first group (Group 1, 12.8% vs Group 2, 31.8%; p < 0.001). On multivariate analysis, wait for ≥ 10 weeks was associated with pathological compete response. Patients from the second group were four time more likely to achieve pathologic complete response than patients from the first group (OR, 4.27 95%CI 1.60-11.40; p = 0.004). Patients who undergo surgery after ≥ 10 weeks of the end of chemoradiotherapy are four time more likely to achieve complete tumor remission without compromise surgical safety or postoperative morbidity.

Reliability evaluation of four different assays for therapeutic drug monitoring of infliximab levels.

BACKGROUND: The aim of this study was to evaluate reliability of four different assays for measuring infliximab trough levels and antibodies to infliximab (ATI). METHODS: In this non-interventional, cross-sectional study including IBD patients, infliximab levels and ATI were measured using four different assays: Lisa-Tracker, Promonitor, Q-Inflixi and Sanquin. Reliability and agreement for infliximab levels was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman plots. Qualitative agreement for infliximab (based on a pre-established target window of trough levels between 3 µg/ml and 7 µg/ml) and for ATI were estimated by Cohen's kappa. RESULTS: Serum samples of 84 IBD patients were evaluated for infliximab using the four assays. Reliability was 'substantial' between Lisa-Tracker versus Promonitor and 'almost perfect' between the remaining assay pairs, with ICCs [95% confidence interval (CI)] ranging from 0.93 (0.70-0.97) for Lisa-Tracker versus Promonitor to 0.97 (0.95-0.98) for Q-Inflixi versus Sanquin. Bland-Altman plots showed significant bias between assays except Promonitor versus Q-Inflixi, which had excellent agreement. The greatest differences in mean infliximab were found between Promonitor versus Lisa-Tracker (-0.91 µg/ml) and Lisa-Tracker versus Q-Inflixi (0.69 µg/ml). Qualitative agreement for infliximab was 'almost perfect' for Promonitor versus Q-Inflixi (kappa 0.84) and Q-Inflixi versus Sanquin (kappa 0.81), and 'substantial' for the remaining pairs. More than 10% of patients who had infliximab levels within the target interval by Lisa-Tracker had suboptimal concentrations (<3 µg/ml) with Promonitor and Q-Inflixi. Furthermore, 11% of patients within the target interval by Q-Inflixi had supra-optimal levels (>7 µg/ml) by Lisa-Tracker. In the remaining paired comparisons, fewer than 5% of patients were placed in different subgroups. Qualitative agreement for ATI fluctuated between 'moderate' and 'almost perfect'. CONCLUSIONS: All four assays seem suitable for therapeutic drug monitoring of infliximab. Promonitor and Q-Inflixi had the best agreement, making those assays fully interchangeable. Systematic biases between Lisa-Tracker with Promonitor and Q-Inflixi suggest that these assays should not be interchanged during the follow up of an individual patient.

Analysis of monoamine oxidase (MAO) enzymatic activity by high-performance liquid chromatography-diode array detection combined with an assay of oxidation with a peroxidase and its application to MAO inhibitors from foods and plants.

Monoamine oxidase (MAO) enzymes catalyze the oxidative deamination of biogenic amines and neurotransmitters and produce ammonia, aldehydes, and hydrogen peroxide which is involved in oxidative processes. Inhibitors of MAO-A and -B isozymes are useful as antidepressants and neuroprotectants. The assays of MAO usually measure amine oxidation products or hydrogen peroxide by spectrophotometric techniques. Those assays are often compromised by interfering compounds resulting in poor results. This research describes a new method that combines in the same assay the oxidative deamination of kynuramine to 4-hydroxyquinoline analyzed by HPLC-DAD with the oxidation of tetramethylbenzidine (TMB) (or Amplex Rex) by horseradish peroxidase (HRP) in presence of hydrogen peroxide. The new method was applied to study the inhibition of human MAO-A and -B by bioactive compounds including ß-carboline alkaloids and flavonoids occurring in foods and plants. As determined by HPLC-DAD, ß-carbolines, methylene blue, kaempferol and clorgyline inhibited MAO-A and methylene blue, 5-nitroindazole, norharman and deprenyl inhibited MAO-B, and all of them inhibited the oxidation of TMB in the same extent. The flavonoids catechin and cyanidin were not inhibitors of MAO by HPLC-DAD but highly inhibited the oxidation of TMB (or Amplex Red) by peroxidase whereas quercetin and resveratrol were moderate inhibitors of MAO-A by HPLC-DAD, but inhibited the peroxidase assay in a higher level. For some phenolic compounds, using the peroxidase-coupled assay to measure MAO activity led to mistaken results. The new method permits to discern between true inhibitors of MAO from those that are antioxidants and which interfere with peroxidase assays but do not inhibit MAO. For true inhibitors of MAO, inhibition as determined by HPLC-DAD correlated well with inhibition of the oxidation of TMB and this approach can be used to assess the in vitro antioxidant activity (less hydrogen peroxide production) resulting from MAO inhibition.

Imported Zika Virus in a European City: How to Prevent Local Transmission?

Background: On February 1st 2016 the WHO declared the Zika Virus (ZIKV) infection a worldwide public health emergency because of its rapid expansion and severe complications, such as Guillain-Barré Syndrome or microcephaly in newborn. The huge amount of people traveling to endemic areas and the presence of Aedes albopictus in Barcelona increase the risk of autochtonous transmission. The objective of this study was to describe the first ZIKV cases diagnosed in our city and to analyze the surveillance, prevention, and control measures implemented to avoid autochthonous transmission. Methods: An observational cross-sectional population-based study in Barcelona, Spain was performed.An analysis of the socio-demographic, epidemiological, clinical characteristics, and mosquito control activities of the ZIKV cases detected between January 1st and December 2016 was carried out using a specific ZIKV epidemiological survey of the Barcelona Public Health Agency. Results: A total of 118 notifications of possible ZIKV infections were received, and 44 corresponded to confirmed cases in Barcelona residents.Amongst these, the median age was 35 years and 57% were women. All cases were imported, 48% were Spanish-born and 52% foreign-born. Dominican Republic was the most visited country amongst foreign-born patients and Nicaragua amongst Spanish-born. The most frequent symptoms were exanthema, fever, and arthralgia. Among the 24 diagnosed women, 6 (25%) were pregnant. There was one case of microcephaly outside Barcelona city. Entomological inspections were done at the homes of 19 cases (43.2% of the total) and in 34 (77.3%) public spaces. Vector activity was found in one case of the 44 confirmed cases, and 134 surveillance and vector control were carried out associated to imported ZIKV cases. In all cases prevention measures were recommended to avoid mosquito bites on infected cases. Conclusion: Epidemiological and entomological surveillance are essential for the prevention of autochthonous transmission of arbovirosis that may have a great impact on Public Health.The good coordination between epidemiologists, entomologists, microbiologists, and clinicians is a priority in a touristic city with an intense relationship with endemic countries to minimize the risk of local transmission by competent vectors.

Anomalous right coronary artery origin with interarterial pathway-importance of morphological origin assessment and the role of percutaneous interventionism.

Anomalies in coronary arteries (CA) are an important issue in cardiology and cardiovascular surgery. Specifically the anomalous origin of the right coronary artery (RCA) is of special importance because it is the most frequent anomaly. Clinical practice guidelines recommend the revascularization treatment in cases of interarterial pathway and documented myocardial ischemia and when hypoplasia, compression or obstruction is evident. We report two different cases of patients with anomalous origin of RCA and associated interarterial pathway. With them we want to highlight the different presentation forms of these patients and the different diagnostic alternatives available in each of the steps. In the patient with anomalous origin of the RCA and associated interarterial pathway, the first step after establishing the diagnosis is to rule out the presence of inducible ischemia. In those patients in whom ischemia induction tests are negative, the second step is to adequately assess the interarterial pathway, in order to rule out obstructions or compressions that also justify revascularization. In those cases in which all the tests are negative, the current evidence does not recommend revascularization, but adequate periodic follow-up is recommended. For this reason, we believe that the stress echocardiogram and exercise perfusion scintigraphy (based on availability and experience in each center) are fundamental because of their high sensitivity and specificity. We would also like to highlight the role that percutaneous interventionism can play in this type of clinical cases. Especially with patients of high surgical risk and in whom the percutaneous approach is feasible.

[Confirmed Dengue, Chikungunya and Zika Cases during the Period 2014 to 2016 in Barcelona, Spain]. / Casos confirmados de Dengue, Chikungunya y Zika en Barcelona capital durante el período de 2014 al 2016.

OBJECTIVE: Arbovirus infections are a group of diseases whose incidence is increasing and that entail an important problem for public health. The aim of this study was to describe detected cases of arbovirosis in Barcelona, and surveillance and control actions performed in order to reduce the risk of transmission. METHODS: Descriptive cross-sectional study of confirmed dengue, chikungunya and Zika cases in Barcelona during 2014-2016 (1st trimester). Suspected cases detected in the city were notified to the Epidemiology Department of the Barcelona Public Health Agency, where an epidemiological survey is undertaken and, if appropriate, Urban Pests Surveillance and Control Department is contacted. They perform an entomological inspection and implement control and monitoring actions. We collected sociodemographical, epidemiological, clinical and entomological variables. RESULTS: In 2014, 50 chikungunya and 20 dengue cases were detected; 25 entomological inspections were carried out in residences and 38 in the street. In 2015, 47 chikungunya, 51 dengue and 2 Zika cases were detected; 27 inspections were carried out in residences and 80 in the street. In 2016, 17 chikungunya, 52 dengue and 48 Zika cases were detected; 50 inspections were carried out in residences and 103 in the street. No autochtonous case was detected. CONCLUSIONS: We observed an increasing incidence of arbovirosis cases during the 3-year study period. There was a progressive intensification of vector surveillance and control actions (inspections, sample collection…).

OBJETIVO: Las infecciones por arbovirus son un grupo de enfermedades cuya incidencia está aumentando y que suponen un problema importante para la salud pública. El objetivo de este estudio fue describir los casos detectados de arbovirosis en la ciudad de Barcelona y las actuaciones de vigilancia y control realizadas para reducir el riesgo de transmisión. METODOS: Estudio descriptivo transversal de casos confirmados de dengue, chikungunya y Zika en Barcelona durante el período de 2014 al 2016. Los casos sospechosos detectados en la ciudad se notificaron al Servicio de Epidemiología de la Agencia de Salud Pública de Barcelona (ASPB), donde se realizó una encuesta epidemiológica y, si procedía, se contactaba con el Servicio de Vigilancia y Control de Plagas Urbanas. Desde allí se realizó la inspección entomológica y se llevaron a cabo acciones de control y seguimiento. Se recogieron variables sociodemográficas, epidemiológicas, clínicas y entomológicas de los casos. RESULTADOS: En 2014 se detectaron 50 casos de virus chikungunya y 20 de dengue, realizándose 25 inspecciones entomológicas en domicilios y 38 en la vía pública. En 2015 se detectaron 47 casos de chikungunya, 51 de dengue y 2 de Zika, realizándose 27 inspecciones entomológicas en domicilios y 80 en vía pública. En 2016 se detectaron 17 casos de chikungunya, 52 de dengue y 48 de Zika, realizándose 50 inspecciones entomológicas en domicilio y 103 en vía pública. No se detectó ningún caso autóctono. CONCLUSIONES: Se observó un aumento creciente de los casos de arbovirosis durante los 3 años de estudio. Se intensificaron progresivamente las actuaciones de vigilancia y control vectorial (inspecciones, muestras recogidas…).

Casos confirmados de Dengue, Chikungunya y Zika en Barcelona capital durante el período de 2014 al 2016 / Confirmed Dengue, Chikungunya and Zika cases during the period 2014 to 2016 in Barcelona, Spain

Fundamentos: Las infecciones por arbovirus son un grupo de enfermedades cuya incidencia está aumentando y que suponen un problema importante para la salud pública. El objetivo de este estudio fue describir los casos detectados de arbovirosis en la ciudad de Barcelona y las actuaciones de vigilancia y control realizadas para reducir el riesgo de transmisión. Métodos: Estudio descriptivo transversal de casos confirmados de dengue, chikungunya y Zika en Barcelona durante el período de 2014 al 2016. Los casos sospechosos detectados en la ciudad se notificaron al Servicio de Epidemiología de la Agencia de Salud Pública de Barcelona (ASPB), donde se realizó una encuesta epidemiológica y, si procedía, se contactaba con el Servicio de Vigilancia y Control de Plagas Urbanas. Desde allí se realizó la inspección entomológica y se llevaron a cabo acciones de control y seguimiento. Se recogieron variables sociodemográficas, epidemiológicas, clínicas y entomológicas de los casos. Resultados: En 2014 se detectaron 50 casos de virus chikungunya y 20 de dengue, realizándose 25 inspecciones entomológicas en domicilios y 38 en la vía pública. En 2015 se detectaron 47 casos de chikungunya, 51 de dengue y 2 de Zika, realizándose 27 inspecciones entomológicas en domicilios y 80 en vía pública. En 2016 se detectaron 17 casos de chikungunya, 52 de dengue y 48 de Zika, realizándose 50 inspecciones entomológicas en domicilio y 103 en vía pública. No se detectó ningún caso autóctono. Conclusiones: Se observó un aumento creciente de los casos de arbovirosis durante los 3 años de estudio. Se intensificaron progresivamente las actuaciones de vigilancia y control vectorial (inspecciones, muestras recogidas…) (AU)

Background: Arbovirus infections are a group of diseases whose incidence is increasing and that entail an important problem for public health. The aim of this study was to describe detected cases of arbovirosis in Barcelona, and surveillance and control actions performed in order to reduce the risk of transmission. Methods: Descriptive cross-sectional study of confirmed dengue, chikungunya and Zika cases in Barcelona during 2014-2016. Suspected cases detected in the city were notified to the Epidemiology Department of the Barcelona Public Health Agency, where an epidemiological survey is undertaken and, if appropriate, Urban Pests Surveillance and Control Department is contacted. They perform an entomological inspection and implement control and monitoring actions. We collected sociodemographical, epidemiological, clinical and entomological variables. Results: In 2014, 50 chikungunya and 20 dengue cases were detected; 25 entomological inspections were carried out in residences and 38 in the street. In 2015, 47 chikungunya, 51 dengue and 2 Zika cases were detected; 27 inspections were carried out in residences and 80 in the street. In 2016, 17 chikungunya, 52 dengue and 48 Zika cases were detected; 50 inspections were carried out in residences and 103 in the street. No autochtonous case was detected. Conclusions: We observed an increasing incidence of arbovirosis cases during the 3-year study period. There was a progressive intensification of vector surveillance and control actions (inspections, sample collection…) (AU)

Nano-ZnO leads to tubulin macrotube assembly and actin bundling, triggering cytoskeletal catastrophe and cell necrosis.

Zinc is a crucial element in biology that plays chief catalytic, structural and protein regulatory roles. Excess cytoplasmic zinc is toxic to cells so there are cell-entry and intracellular buffering mechanisms that control intracellular zinc availability. Tubulin and actin are two zinc-scavenging proteins that are essential components of the cellular cytoskeleton implicated in cell division, migration and cellular architecture maintenance. Here we demonstrate how exposure to different ZnO nanostructures, namely ZnO commercial nanoparticles and custom-made ZnO nanowires, produce acute cytotoxic effects in human keratinocytes (HaCat) and epithelial cells (HeLa) triggering a dose-dependent cell retraction and collapse. We show how engulfed ZnO nanoparticles dissolve intracellularly, triggering actin filament bundling and structural changes in microtubules, transforming these highly dynamic 25 nm diameter polymers into rigid macrotubes of tubulin, severely affecting cell proliferation and survival. Our results demonstrate that nano-ZnO causes acute cytoskeletal collapse that triggers necrosis, followed by a late reactive oxygen species (ROS)-dependent apoptotic process.

Inhibition of Cancer Cell Migration by Multiwalled Carbon Nanotubes.

Inhibiting cancer cell migration and infiltration to other tissues makes the difference between life and death. Multiwalled carbon nanotubes (MWCNTs) display intrinsic biomimetic properties with microtubules, severely interfering with the function of these protein filaments during cell proliferation, triggering cell death. Here it is shown MWCNTs disrupt the centrosomal microtubule cytoskeletal organization triggering potent antimigratory effects in different cancer cells.

Multiwalled carbon nanotubes hinder microglia function interfering with cell migration and phagocytosis.

The intranasal drug delivery route provides exciting expectations regarding the application of engineered nanomaterials as nano-medicines or drug-delivery vectors into the brain. Among nanomaterials, multiwalled CNTs (MWCNTs) are some of the best candidates for brain cancer therapy since they are well known to go across cellular barriers and display an intrinsic ability to block cancer cell proliferation triggering apoptosis. This study reveals that microglial cells, the brain macrophages and putative vehicles for MWCNTs into the brain, undergo a dose-dependent cell division arrest and apoptosis when treated with MWCNTs. Moreover, it is shown that MWCNTs severely interfere with both cell migration and phagocytosis in live microglia. These results lead to a re-evaluation of the safety of inhaled airborne CNTs and provide strategic clues of how to biocompatibilize MWCNTs to reduce brain macrophage damage and to develop new nanodrugs.

Multiwalled carbon nanotubes display microtubule biomimetic properties in vivo, enhancing microtubule assembly and stabilization.

Microtubules are hollow protein cylinders of 25 nm diameter which are implicated in cytokinetics and proliferation in all eukaryotic cells. Here we demonstrate in vivo how multiwalled carbon nanotubes (MWCNTs) interact with microtubules in human cancer cells (HeLa) blocking mitosis and leading to cell death by apoptosis. Our data suggest that, inside the cells, MWCNTs display microtubule biomimetic properties, assisting and enhancing noncentrosomal microtubule polymerization and stabilization. These features might be useful for developing a revolutionary generation of chemotherapeutic agents based on nanomaterials.

Síndrome poliglandular autoinmunitario tipo 1. Diferentes formas de inicio / Polyglandular autoimmune syndrome type 1. Different onset forms

No disponible

Contribution of endermology to improving indurations and panniculitis/lipoatrophy at glatiramer acetate injection site.

INTRODUCTION: Endermology is a mechanical massage therapy that enables fat mobilization and body contouring. The authors' aim was to assess the effect of endermology on indurations and panniculitis/lipoatrophy associated with subcutaneous administration of glatiramer acetate in patients with multiple sclerosis (MS). METHODS: This was a multicenter pilot experience carried out in patients with MS treated with glatiramer acetate who showed indurations and/ or panniculitis/lipoatrophy at the injection site. Patients underwent endermology and glatiramer acetate treatment according to clinical practice. The primary endpoint was the change in indurations and/or panniculitis/lipoatrophy after 12 endermology sessions. RESULTS: Between April and July 2011, a total of 13 evaluable patients were included (mean age, 40.7±3.1 years; female, 100%; white, 100%; mean MS duration, 10.1±2.3 years; previous MS treatment, 46.2%; mean glatiramer acetate treatment duration, 27.3±9.5 months). Eleven patients (84.6%) showed local indurations (mean diameter, 3.4±0.5 cm; mean number, 9.0±1.0) and six patients (46.2%) areas of panniculitis/ lipoatrophy (mean number, 5.0±1.1). After 12 endermology sessions, patients with indurations reported having experienced a reduction in size (10 patients [90.9%]; mean diameter, 0.1±0.05 cm; P<0.001) and number of indurations (nine patients [81.8%]; mean number, 2.3±1.1; P<0.005). These indurations completely disappeared from arms, thighs, buttocks, and abdomen in six (75.0%), six (75.0%), two (50.0%), and three (42.9%) patients, respectively. Three of these patients (27.3%) recovered from all indurations. Although panniculitis/lipoatrophy did not completely disappear, all patients reported improvements. Most patients with indurations (63.6%) felt very satisfied and considered endermology very useful for reducing indurations. All patients with panniculitis/lipoatrophy were satisfied and considered to be endermology useful in improving it. In addition, endermology enabled glatiramer acetate tolerance to be improved in most patients (60.0%). CONCLUSION: Endermology may contribute to improving indurations and panniculitis/ lipoatrophy at the site of subcutaneous injection of glatiramer acetate in patients with MS, enabling areas of injection to recover, and treatment tolerance to increase.

Improvement of the quality of lumazine synthase crystals by protein engineering.

Icosahedral macromolecules have a wide spectrum of potential nanotechnological applications, the success of which relies on the level of accuracy at which the molecular structure is known. Lumazine synthase from Bacillus subtilis forms a 150 A icosahedral capsid consisting of 60 subunits and crystallizes in space group P6(3)22 or C2. However, the quality of these crystals is poor and structural information is only available at 2.4 A resolution. As classical strategies for growing better diffracting crystals have so far failed, protein engineering has been employed in order to improve the overexpression and purification of the molecule as well as to obtain new crystal forms. Two cysteines were replaced to bypass misfolding problems and a charged surface residue was replaced to force different molecular packings. The mutant protein crystallizes in space group R3, with unit-cell parameters a = b = 313.02, c = 365.77 A, alpha = beta = 90.0, gamma = 120 degrees , and diffracts to 1.6 A resolution.

Photocatalytic ozonation of phenolic wastewaters: Syringic acid, tyrosol and gallic acid.

The photocatalytic ozonation of a mixture of 3 phenols (gallic acid, tyrosol and syringic acid) has been conducted under different operating conditions. The individual adsorption of the phenol type compounds onto titanium dioxide (photocatalyst) has been first evaluated. Equilibrium conditions are attained in less than an hour while the isotherm curves reveal that adsorption intensity increases in order: syringic acid < tyrosol < gallic acid. When the photocatalytic ozonation is applied, an optimum in titanium dioxide concentration is experienced (1.5 g L(-1)). Direct comparison of the photocatalytic ozonation to other less sophisticated oxidation systems (i.e., single ozonation, catalytic ozonation, photo-ozonation, etc.) indicates a higher efficiency of the former in terms of ozone uptake.