Novel Titanocene Y derivative with albumin affinity exhibits improved anticancer activity against platinum resistant cells.

The antitumor activity of Ti(IV)-based compounds put them in the spotlight for cancer treatment in the past, but their lack of stability in vivo due to a high rate of hydrolysis has hindered their development as antitumor drugs. As a possible solution for this problem, we have reported a synthesis strategy through which we combined a titanocene fragment, a tridentate ligand, and a long aliphatic chain. This strategy allowed us to generate a titanium compound (Myr-Ti) capable of interacting with albumin, highly stable in water and with cytotoxic activity in tumor cells[1]. Following a similar strategy, now we report the synthesis of a new compound (Myr-TiY) derived from titanocene Y that shows antitumoral activity in a cisplatin resistant model with a 50% inhibitory concentration (IC50) of 41-76 µM. This new compound shows high stability and a strong interaction with human serum albumin. Myr-TiY has a significant antiproliferative and proapoptotic effect on the tested cancer cells and shows potential tumor selectivity when assayed in non-tumor human epithelial cells being more selective (1.3-3.8 times) for tumor cells than cisplatin. These results lead us to think that the described synthesis strategy could be useful to generate compounds for the treatment of both cisplatin-sensitive and cisplatin-resistant cancers.

Biological evaluation of carbohydrate-based aprepitant analogs for neuroblastoma treatment.

Different studies using Aprepitant, a NK1R antagonist currently used as a clinical drug for treating chemotherapy-related nausea and vomiting, have demonstrated that pharmacological inhibition of NK1R effectively reduces the growth of several tumor types such as neuroblastoma (NB). In a previous work, we demonstrated that a series of carbohydrate-based Aprepitant analogs, derived from either d-galactose or l-arabinose, have shown high affinity and NK1R antagonistic activity with a broad-spectrum anticancer activity and an important selectivity. In this new study, we explore the selective cytotoxic effects of these derivatives for the treatment of NB. Furthermore, we describe the design and stereoselective synthesis of a new generation of d-glucose derivatives as Aprepitant analogs, supported by docking studies. This approach showed that most of our carbohydrate-based analogs are significantly more selective than Aprepitant. The galactosyl derivative 2α, has demonstrated a marked in vitro selective cytotoxic activity against NB, with IC50 values in the same range as those of Aprepitant and its prodrug Fosaprepitant. Interestingly, the derivative 2α has shown similar apoptotic effect to that of Aprepitant. Moreover, we can select the glucosyl amino derivative 10α as an interesting hit exhibiting higher in vitro cytotoxic activity against NB than Aprepitant, being 1.2 times more selective.

[Results of the Implementation of a Case-Finding Program for Alpha-1 Antitrypsin Deficiency in COPD Patients]. / Resultados de la implementación de un programa de detección de casos de déficit de alfa-1 antitripsina en pacientes con EPOC.

Objectives: Currently, the identification of new cases of alpha-1 antitrypsin deficiency (AATD) continues to be one of the great challenges facing the disease. The present study aims to perform an analysis of the results of the implementation of a systematic case detection program of AATD for patients with chronic obstructive pulmonary disease. Material and methods: Cross-sectional observational study in which the results of AAT screening until December 2022 were analyzed. The cases studied were divided into three periods: (1) no systematic case detection until 2013; (2) systematic case detection of S and Z alleles for cases with AAT < 90 mg/dL until 2018, and (3) systematic case detection of 14 mutations for cases with AAT < 120 mg/dL since 2018. Results: A total of 471 cases were studied, of which 306 (65.0%) were carriers of some mutation related to HAD. The number of detected cases of all mutations with their percentage against those studied in each period was respectively: 6 (100%), 48 (88.8%) and 253 (61.5%). If we limit to severe mutations (AAT < 57.2 mg/dL), the distribution by periods was respectively: 3 (50.0), 10 (18.5%) and 17 (4.1%). Conclusions: The present study describes the changes in the detection of patients carrying DAAT-related alleles with three different case identification policies. The data support the use of systematic case detection system in the COPD patient population.

Nefropatía endémica mesoamericana: una enfermedad renal crónica de origen no tan desconocido / Mesoamerican nephropathy: A not so unknown chronic kidney disease

Desde el año 2000, la región de Mesoamérica ha presentado una elevada incidencia de casos de enfermedad renal crónica de origen desconocido. Bajo el nombre de nefropatía endémica mesoamericana (NeM) han concurrido numerosas hipótesis incluyendo la deshidratación, el estrés por calor, la exposición a contaminantes ambientales e incluso determinadas infecciones, sin que actualmente exista unanimidad en la etiología de dicha patología. La NeM afecta principalmente a varones jóvenes dedicados a actividades agrícolas con antecedente de exposición a temperaturas especialmente elevadas. Clínicamente cursa con síntomas inespecíficos como febrícula y disuria y, analíticamente, con deterioro de la función renal y alteraciones hidroelectrolíticas. El diagnóstico exige de la realización de una biopsia renal que muestra invariablemente datos de nefritis tubulointersticial, principalmente crónica. A pesar de que la NeM condiciona una elevada morbimortalidad en las regiones endémicas, no existe un tratamiento específico, por lo que la prevención, basada en disminuir la exposición a elevadas temperaturas y asegurar el correcto estado de hidratación son de gran importancia. En la presente revisión, y basándonos en un caso clínico, actualizamos la evidencia disponible sobre un problema de salud pública con relevantes consecuencias renales. (AU)

From 2000, Mesoamerican region has reached an important rate of chronic kidney disease of unknown etiology. Under the name of Meroamerican Nephropathy (MeN) several hypotheses (including dehydration, heat stress, environmental or toxic exposure or even infections) have tried to explain the etiology this new disease. MeN affects young men, agricultural workers exposed to high temperatures. MeN courses with unspecific symptoms as low-grade fever and dysuria and progressive kidney disease with impaired renal function and hydroelectrolyte disturbances. The diagnosis requires kidney biopsy showing tubule-interstitial nephritis (usually at chronic stage). Although MeN conditions a high morbi-mortality in endemic regions, there is a lack of specific treatment and only preventive measures have demonstrated some effect of prognosis (avoid heat stress, constant hydration). In this review we aim to summarize the available information of MeN, illustrating the information in a case report. (AU)

New titanocene derivative with improved stability and binding ability to albumin exhibits high anticancer activity.

Titanium-based therapies have emerged as a promising alternative for the treatment of cancer patients, particularly those with cisplatin resistant tumors. Unfortunately, some titanium compounds show stability and solubility problems that have hindered their use in clinical practice. Here, we designed and synthesized a new titanium complex containing a titanocene fragment, a tridentate ligand to improve its stability in water, and a long aliphatic chain, designed to facilitate a non-covalent interaction with albumin, the most abundant protein in human serum. The stability and human serum albumin affinity of the resulting titanium complex was investigated by UV-Vis absorption and fluorescence spectroscopy techniques. Complex [TiCp2{(OOC)2py-O-myr}] (3) (myr = C14H29, py = pyridine) and its analogous [TiCp2{(OOC)2py-OH}] (4), lacking the aliphatic chain, showed improved stability in phosphate saline buffer compared with [TiCp2Cl2] (1). 3 showed a strong interaction with human serum albumin in a 1:1 stoichiometry. The cytotoxic effect of 3 was higher compared to [TiCp2Cl2] in tumor cell lines and showed potential tumor selectivity when assayed in non-tumor human epithelial cells. Finally, 3 showed an antiproliferative effect on cancer cells, decreasing the population in the S phase, and increasing apoptotic cells in a significant manner. All this makes the novel Ti(IV) compound 3 a firm candidate to continue further studies of its therapeutic potential in vitro and in vivo.

Mesoamerican nephropathy: A not so unknown chronic kidney disease. / Nefropatía endémica mesoamericana: una enfermedad renal crónica de origen no tan desconocido.

From 2000, Mesoamerican region has reached an important rate of chronic kidney disease of unknown etiology. Under the name of Meroamerican Nephropathy (MeN) several hypotheses (including dehydration, heat stress, environmental or toxic exposure or even infections) have tried to explain the etiology this new disease. MeN affects young men, agricultural workers exposed to high temperatures. MeN courses with unspecific symptoms as low-grade fever and dysuria and progressive kidney disease with impaired renal function and hydroelectrolyte disturbances. The diagnosis requires kidney biopsy showing tubule-interstitial nephritis (usually at chronic stage). Although MeN conditions a high morbi-mortality in endemic regions, there is a lack of specific treatment and only preventive measures have demonstrated some effect of prognosis (avoid heat stress, constant hydration). In this review we aim to summarize the available information of MeN, illustrating the information in a case report.

The heterogeneity of reversion to normoglycemia according to prediabetes type is not explained by lifestyle factors.

Healthy lifestyle interventions and drug therapies are proven to have a positive preventative influence on normal glucose regulation in prediabetes. However, little is known on the specific role that these factors play on reversion to normal glycemia according to type of prediabetes. We used data from the Observational prospective cohort study, The Cohort study in Primary Health Care on the Evolution of Patients with Prediabetes from 2012 to 2015. A total of 1184 individuals aged 30-74 years old were included and classified based on the ADA in three mutually exclusive groups using either fasting plasma glucose (FPG) levels (from 100 to 125 mg/dl, FPG group), HbA1c (5.7-6.4%, HbA1c group) or both impaired parameters. Information on lifestyle factors and biochemical parameters were collected at baseline. Reversion to normal glucose regulation was calculated at third year of follow-up. Relationship of lifestyle factor and type of prediabetes with reversion were estimated using odds ratios (ORs) with 95% confidence intervals (95% CIs) adjusting by different groups of confounders. Proportion of reversion rates were 31% for FPG group, 31% for HbA1c group and 7.9% for both altered parameters group, respectively. Optimal life style factors such as BMI < 25 kg/m2[OR (95% CI): 1.90 (1.20-3.01)], high adherence to Mediterranean diet 1.78 (1.21-2.63) and absence of abdominal obesity 1.70 (1.19-2.43) were the strongest predictors for reversion to normal glucose. However, those did not modify the ORs of reversion to normal glucose. Taking as reference those with both impaired parameters, subjects with FPG impairment (FPG group) had an OR of 4.87 (3.10-7.65) and 3.72 (2.39-5.78) for HbA1c group. These estimates remained almost the same after further adjustment for biochemical parameters and lifestyle factors (4.55(2.84-7.28) and 3.09 (1.92-4.97), respectively). Optimal lifestyle factors showed to be a positive predictor for reversion to normal glucose regulation however, the differences of reversion risk according type of prediabetes are not explained by lifestyle factors.

Mesoamerican nephropathy: A not so unknown chronic kidney disease.

From 2000, Mesoamerican region has reached an important rate of chronic kidney disease of unknown etiology. Under the name of Meroamerican Nephropathy (MeN) several hypotheses (including dehydration, heat stress, environmental or toxic exposure or even infections) have tried to explain the etiology this new disease. MeN affects young men, agricultural workers exposed to high temperatures. MeN courses with unspecific symptoms as low-grade fever and dysuria and progressive kidney disease with impaired renal function and hydroelectrolyte disturbances. The diagnosis requires kidney biopsy showing tubule-interstitial nephritis (usually at chronic stage). Although MeN conditions a high morbi-mortality in endemic regions, there is a lack of specific treatment and only preventive measures have demonstrated some effect of prognosis (avoid heat stress, constant hydration). In this review we aim to summarize the available information of MeN, illustrating the information in a case report.

Acute hepatitis due to olmesartan: an uncommon entity.

We report the case of a hypertensive 54-year-old female who had been under treatment with olmesartan (40 mg daily) for a month. She was referred due to hypertransaminasemia and also reported asthenia and a 7 kg weight loss.

Adiposity and Diabetes Risk in Adults with Prediabetes: Heterogeneity of Findings Depending on Age and Anthropometric Measure.

OBJECTIVE: The study aimed to evaluate the effect of age on diabetes incidence by general and central adiposity after 3-year follow-up in adults with prediabetes. METHODS: Data were taken from a cohort of 1,184 subjects with prediabetes included in The Cohort Study in Primary Health Care on the Evolution of Patients with Prediabetes (PREDAPS). General adiposity was defined using body mass index (BMI), and central adiposity was defined with waist circumference and waist to height ratio. Data were analyzed by age groups 30 to 59 and 60 to 74 years. The association between adiposity and diabetes incidence was assessed using hazard ratios (HR). RESULTS: Adjusting for sociodemographic characteristics, lifestyles, and metabolic parameters, diabetes HR for central adiposity based on the waist circumference clinical cutoff were 2.14 (1.12-4.09) and 1.48 (0.80-2.74) for people aged 30 to 59 and 60 to 74 years, respectively. In the model additionally adjusted for BMI, diabetes HR were 2.65 (1.24-5.65) and 1.33 (0.68-2.59), respectively. The use of a 1-SD increase rather than cutoff points did not alter this pattern. Similar findings were observed with central adiposity based on waist to height ratio. CONCLUSIONS: The association of central adiposity with type 2 diabetes incidence was lower for people in the older age group than for those in the younger age group.

Asociación de obesidad general y abdominal con hipertensión, dislipemia y presencia de prediabetes en el estudio PREDAPS / Association of general and abdominal obesity with hypertension, dyslipidemia and prediabetes in the PREDAPS study

Introducción y objetivos: Algunas medidas antropométricas muestran mayor capacidad que otras para discriminar la presencia de factores de riesgo cardiovascular. Este trabajo estima la magnitud de la asociación de diversos indicadores antropométricos de obesidad con hipertensión, dislipemia y prediabetes (glucemia basal o glucohemoglobina alteradas). Métodos: Análisis transversal de la información recogida en 2.022 sujetos del estudio PREDAPS (etapa basal). Se definió obesidad general como índice de masa corporal ≥ 30 kg/m2 y obesidad abdominal con 2 criterios: a) perímetro de cintura (PC) ≥ 102 cm en varones/PC ≥ 88 cm en mujeres, y b) índice cintura/estatura (ICE) ≥ 0,55. La magnitud de la asociación se estimó mediante regresión logística. Resultados: La hipertensión arterial mostró la asociación más alta con la obesidad general en mujeres (OR = 3,01; IC95%, 2,24-4,04) y con la obesidad abdominal según el criterio del ICE en varones (OR = 3,65; IC95%, 2,66-5,01). La hipertrigliceridemia y los valores bajos de colesterol unido a lipoproteínas de alta densidad mostraron la asociación más alta con obesidad abdominal según el criterio del ICE en mujeres (OR = 2,49; IC95%, 1,68-3,67 y OR = 2,70; IC95%, 1,89-3,86) y la obesidad general en varones (OR = 2,06; IC95%, 1,56-2,73 y OR = 1,68; IC95%, 1,21-2,33). La prediabetes mostró la asociación más alta con obesidad abdominal según el criterio del ICE en mujeres (OR = 2,48; IC95%, 1,85-3,33) y con obesidad abdominal según el criterio del PC en varones (OR = 2,33; IC95%, 1,75-3,08). Conclusiones: Los indicadores de obesidad abdominal mostraron la mayor asociación con la presencia de prediabetes. La relación de los indicadores antropométricos con hipertensión y con dislipemia mostró resultados heterogéneos (AU)

Introduction and objectives: Some anthropometric measurements show a greater capacity than others to identify the presence of cardiovascular risk factors. This study estimated the magnitude of the association of different anthropometric indicators of obesity with hypertension, dyslipidemia, and prediabetes (altered fasting plasma glucose and/or glycosylated hemoglobin). Methods: Cross-sectional analysis of information collected from 2022 participants in the PREDAPS study (baseline phase). General obesity was defined as body mass index ≥ 30 kg/m2 and abdominal obesity was defined with 2 criteria: a) waist circumference (WC) ≥ 102 cm in men/WC ≥ 88 cm in women, and b) waist-height ratio (WHtR) ≥ 0.55. The magnitude of the association was estimated by logistic regression. Results: Hypertension showed the strongest association with general obesity in women (OR, 3.01; 95%CI, 2.24-4.04) and with abdominal obesity based on the WHtR criterion in men (OR, 3.65; 95%CI, 2.66-5.01). Hypertriglyceridemia and low levels of high-density lipoprotein cholesterol showed the strongest association with abdominal obesity based on the WHtR criterion in women (OR, 2.49; 95%CI, 1.68-3.67 and OR, 2.70; 95%CI, 1.89-3.86) and with general obesity in men (OR, 2.06; 95%CI, 1.56-2.73 and OR, 1.68; 95%CI, 1.21-2.33). Prediabetes showed the strongest association with abdominal obesity based on the WHtR criterion in women (OR, 2.48; 95%CI, 1.85-3.33) and with abdominal obesity based on the WC criterion in men (OR, 2.33; 95%CI, 1.75-3.08). Conclusions: Abdominal obesity indicators showed the strongest association with the presence of prediabetes. The association of anthropometric indicators with hypertension and dyslipidemia showed heterogeneous results (AU)

Association of General and Abdominal Obesity With Hypertension, Dyslipidemia and Prediabetes in the PREDAPS Study.

INTRODUCTION AND OBJECTIVES: Some anthropometric measurements show a greater capacity than others to identify the presence of cardiovascular risk factors. This study estimated the magnitude of the association of different anthropometric indicators of obesity with hypertension, dyslipidemia, and prediabetes (altered fasting plasma glucose and/or glycosylated hemoglobin). METHODS: Cross-sectional analysis of information collected from 2022 participants in the PREDAPS study (baseline phase). General obesity was defined as body mass index ≥ 30kg/m2 and abdominal obesity was defined with 2 criteria: a) waist circumference (WC) ≥ 102cm in men/WC ≥ 88cm in women, and b) waist-height ratio (WHtR) ≥ 0.55. The magnitude of the association was estimated by logistic regression. RESULTS: Hypertension showed the strongest association with general obesity in women (OR, 3.01; 95%CI, 2.24-4.04) and with abdominal obesity based on the WHtR criterion in men (OR, 3.65; 95%CI, 2.66-5.01). Hypertriglyceridemia and low levels of high-density lipoprotein cholesterol showed the strongest association with abdominal obesity based on the WHtR criterion in women (OR, 2.49; 95%CI, 1.68-3.67 and OR, 2.70; 95%CI, 1.89-3.86) and with general obesity in men (OR, 2.06; 95%CI, 1.56-2.73 and OR, 1.68; 95%CI, 1.21-2.33). Prediabetes showed the strongest association with abdominal obesity based on the WHtR criterion in women (OR, 2.48; 95%CI, 1.85-3.33) and with abdominal obesity based on the WC criterion in men (OR, 2.33; 95%CI, 1.75-3.08). CONCLUSIONS: Abdominal obesity indicators showed the strongest association with the presence of prediabetes. The association of anthropometric indicators with hypertension and dyslipidemia showed heterogeneous results.

Cardiometabolic Risk Profiles in Patients With Impaired Fasting Glucose and/or Hemoglobin A1c 5.7% to 6.4%: Evidence for a Gradient According to Diagnostic Criteria: The PREDAPS Study.

It has been suggested that the early detection of individuals with prediabetes can help prevent cardiovascular diseases. The purpose of the current study was to examine the cardiometabolic risk profile in patients with prediabetes according to fasting plasma glucose (FPG) and/or hemoglobin A1c (HbA1c) criteria.Cross-sectional analysis from the 2022 patients in the Cohort study in Primary Health Care on the Evolution of Patients with Prediabetes (PREDAPS Study) was developed. Four glycemic status groups were defined based on American Diabetes Association criteria. Information about cardiovascular risk factors-body mass index, waist circumference, blood pressure, cholesterol, triglycerides, uric acid, gamma-glutamyltransferase, glomerular filtration-and metabolic syndrome components were analyzed. Mean values of clinical and biochemical characteristics and frequencies of metabolic syndrome were estimated adjusting by age, sex, educational level, and family history of diabetes.A linear trend (P < 0.001) was observed in most of the cardiovascular risk factors and in all components of metabolic syndrome. Normoglycemic individuals had the best values, individuals with both criteria of prediabetes had the worst, and individuals with only one-HbA1c or FPG-criterion had an intermediate position. Metabolic syndrome was present in 15.0% (95% confidence interval: 12.6-17.4), 59.5% (54.0-64.9), 62.0% (56.0-68.0), and 76.2% (72.8-79.6) of individuals classified in normoglycemia, isolated HbA1c, isolated FPG, and both criteria groups, respectively.In conclusion, individuals with prediabetes, especially those with both criteria, have worse cardiometabolic risk profile than normoglycemic individuals. These results suggest the need to use both criteria in the clinical practice to identify those individuals with the highest cardiovascular risk, in order to offer them special attention with intensive lifestyle intervention programs.

Modifiable risk factors associated with prediabetes in men and women: a cross-sectional analysis of the cohort study in primary health care on the evolution of patients with prediabetes (PREDAPS-Study).

BACKGROUND: Prediabetes is a high-risk state for diabetes development, but little is known about the factors associated with this state. The aim of the study was to identify modifiable risk factors associated with the presence of prediabetes in men and women. METHODS: Cohort Study in Primary Health Care on the Evolution of Patients with Prediabetes (PREDAPS-Study) is a prospective study on a cohort of 1184 subjects with prediabetes and another cohort of 838 subjects without glucose metabolism disorders. It is being conducted by 125 general practitioners in Spain. Data for this analysis were collected during the baseline stage in 2012. The modifiable risk factors included were: smoking habit, alcohol consumption, low physical activity, inadequate diet, hypertension, dyslipidemia, and obesity. To assess independent association between each factor and prediabetes, odds ratios (ORs) were estimated using logistic regression models. RESULTS: Abdominal obesity, low plasma levels of high-density lipoprotein cholesterol (HDL-cholesterol), and hypertension were independently associated with the presence of prediabetes in both men and women. After adjusting for all factors, the respective ORs (95% Confidence Intervals) were 1.98 (1.41-2.79), 1.88 (1.23-2.88) and 1.86 (1.39-2.51) for men, and 1.89 (1.36-2.62), 1.58 (1.12-2.23) and 1.44 (1.07-1.92) for women. Also, general obesity was a risk factor in both sexes but did not reach statistical significance among men, after adjusting for all factors. Risky alcohol consumption was a risk factor for prediabetes in men, OR 1.49 (1.00-2.24). CONCLUSIONS: Obesity, low HDL-cholesterol levels, and hypertension were modifiable risk factors independently related to the presence of prediabetes in both sexes. The magnitudes of the associations were stronger for men than women. Abdominal obesity in both men and women displayed the strongest association with prediabetes. The findings suggest that there are some differences between men and women, which should be taken into account when implementing specific recommendations to prevent or delay the onset of diabetes in adult population.

[Clinical practice guideline for the diagnosis and treatment of hyperprolactinemia]. / Guía de práctica clínica para el diagnóstico y tratamiento de la hiperprolactinemia.

BACKGROUND: Hyperprolactinemia is a common finding within clinical practice in both endocrinology and general practice fields, amongst other specialties. The general practitioner and other specialists must know the indications and serum prolactin determination parameters in order to, once detected, derive the patient for a correct assessment and begin treatment. OBJECTIVE: Formulate a clinical practice guideline evidence-based for the diagnosis and treatment of hyperprolactinemia. METHOD: It took the participation of eight gynecologists, two pathologists and a pharmacologist in the elaboration of this guideline due their experience and clinical judgement. These recommendations were based upon diagnostic criteria and levels of evidence from treatment guidelines previously established, controlled clinical trials and standardized guides for adolescent and adult population with hyperprolactinemia. RESULTS: During the conformation of this guideline each specialist reviewed and updated a specific topic and established the evidence existent over different topics according their field of best clinical expertise, being enriched by the opinion of other experts. At the end, all the evidence and decisions taken were unified in the document presented here. CONCLUSIONS: It is presented the recommendations established by the panel of experts for diagnosis and treatment of patients with high levels of prolactin; also the level of evidence for the diagnosis of hyperprolactinemia, handling drug-induced hyperprolactinemia and prolactinomas in pregnant and non-pregnant patients.

Sunitinib suppress neuroblastoma growth through degradation of MYCN and inhibition of angiogenesis.

Neuroblastoma, a tumor of the peripheral sympathetic nervous system, is the most common and deadly extracranial tumor of childhood. The majority of high-risk neuroblastoma exhibit amplification of the MYCN proto-oncogene and increased neoangiogenesis. Both MYCN protein stabilization and angiogenesis are regulated by signaling through receptor tyrosine kinases (RTKs). Therefore, inhibitors of RTKs have a potential as a treatment option for high-risk neuroblastoma. We used receptor tyrosine kinase antibody arrays to profile the activity of membrane-bound RTKs in neuroblastoma and found the multi-RTK inhibitor sunitinib to tailor the activation of RTKs in neuroblastoma cells. Sunitinib inhibited several RTKs and demonstrated potent antitumor activity on neuroblastoma cells, through induction of apoptosis and cell cycle arrest. Treatment with sunitinib decreased MYCN protein levels by inhibition of PI3K/AKT signaling and GSK3ß. This effect correlates with a decrease in VEGF secretion in neuroblastoma cells with MYCN amplification. Sunitinib significantly inhibited the growth of established, subcutaneous MYCN-amplified neuroblastoma xenografts in nude mice and demonstrated an anti-angiogenic effect in vivo with a reduction of tumor vasculature and a decrease of MYCN expression. These results suggest that sunitinib should be tested as a treatment option for high risk neuroblastoma patients.

A new time limited psychotherapy for BPD: preliminary results of a randomized and controlled trial.

INTRODUCTION: Psychic Representation focused Psychotherapy (PRFP) is a new time limited dynamic psychotherapy for the treatment of Borderline Personality Disorder. It is a psychodynamic technique based on brief psychoanalytic psychotherapy principles. It is manualized and designed to be applied in the framework of public health care services. A randomized and controlled study with a sample of 53 patients was conducted to assess PRFP efficacy. This work presents the results for the first 44 trial completers at termination of treatment. METHODS: Both groups, the experimental (n= 18) and control group (n= 26), received treatment as usual. The experimental group received an additional 20 (PRFP) sessions, conducted by four therapists with homogenous characteristics specifically trained in this technique. The main outcome variables measures were: Severity global index of SCL-90-R, Barrat Impulsivity Scale scores and Social Adaptation (SASS score). Baseline and final condition at termination was compared. CONCLUSIONS: Preliminary results showed significantly better outcomes for the experimental group in all the main variables measured and in most of the secondary ones. PRFP may represent an important contribution for the treatment of BPD patients. Follow-up assessment at 6 and 12 months is planned.

[Cohort Study in Primary Health Care on the Evolution of Patients with Prediabetes (PREDAPS): basis and methodology].

The PREDAPS study aims to determine the risk of developing diabetes and the risk of vascular complications in patients with prediabetes and identify factors associated with those risks. It is a prospective observational study of a cohort of 1184 subjects with prediabetes and another cohort of 838 subjects with no alterations in glucose metabolism. The data at baseline were obtained from patients attending primary care centers in Spain throughout 2012. Subjects with prediabetes were classified into three groups: those who had only altered the fasting blood glucose levels -between 100 and 125mg/dl-, those who had only altered the HbA1c level -between 5.7 and 6.4% - and those who had altered both parameters. Information on sociodemographic characteristics, personal and family history, lifestyle and drug therapy was obtained from medical records and the interview with the doctor in the consultation. It was also performed a physical examination to determine weight, height, waist circumference and blood pressure were performed and blood and urine analysis. The PREDAPS study may help to reduce uncertainty in individual prevention strategies in subjects with prediabetes. Annual monitoring of patients recruited for five years will enable to know the risk of developing diabetes type 2 and the risk of macro-and microvascular complications in the three groups of subjects with prediabetes and determine the factors associated with those risks.