Delivering aminopyridine ligands into cancer cells through conjugation to the cell-penetrating peptide BP16.

Peptide conjugates incorporating the N-based ligands (Me2)PyTACN or (S,S')-BPBP at the N- or the C-terminus of the cell-penetrating peptide were synthesized (PyTACN-BP16 (), BP16-PyTACN (), BPBP-BP16 (), and BP16-BPBP ()). Metal binding peptides bearing at the N-terminus the ligand, an additional Lys and a ß-Ala were also prepared (PyTACN-ßAK-BP16 () and BPBP-ßAK-BP16 ()). Moreover, taking into account the clathrin-dependent endocytic mechanism of , the enzymatic cleavable tetrapeptide Gly-Phe-Leu-Gly was incorporated between the ligand and the N- or C-terminus of (BPBP-GFLG-BP16 () and BP16-GLFG-BPBP ()). Analysis of the cytotoxicity of all the peptide conjugates showed that: (i) the position of the ligand influenced the IC50 values, (ii) the incorporation of the ßAla-Lys dipeptide rendered non active sequences, (iii) peptide conjugates derived from the (S,S')-BPBP ligand were more active than those bearing (Me2)PyTACN, and (iv) the introduction of the cleavable tetrapeptide significantly enhanced the activity of the BPBP conjugates (IC50 of 4.3 to 11.7 µM ( and ) compared to 26.0 to >50 µM (, and )). The most active peptide was BPBP-GFLG-BP16 () (IC50 of 4.3 to 5.0 µM). This high activity was attributed to its high internalization in MCF-7 cells, as shown by flow cytometry, and to the subsequent release of the ligand by the intracellular cleavage of the enzyme-labile spacer, as observed in cathepsin B enzymatic assays. Therefore, these results pave the way for the design of novel peptide conjugates to be used in pro-oxidant anticancer therapies.

Detection of volatile organic compounds using flexible gas sensing devices based on tungsten oxide nanostructures functionalized with Au and Pt nanoparticles.

Flexible gas sensor devices are fabricated and optimized by integrating directly, via a single-step vapor-phase deposition method, highly crystalline tungsten oxide nanostructures functionalized with either gold or platinum nanoparticles. Gas tests of these devices show significant improvements with respect to flexible gas sensors based on non-functionalized structures, including greater responses to various volatile organic compounds (ethanol, acetone, methanol and toluene) and better selectivity towards ethanol and methanol, as demonstrate results for the sensors based on platinum-functionalized structures. The method presented here, which includes the fabrication of the whole flexible gas sensing device and the integration of functional nanostructures without the use of transfer methods, provides a simpler, faster and inexpensive method for the fabrication of highly functional flexible microsystems for gas sensing.

Review on ion mobility spectrometry. Part 1: current instrumentation.

Ion Mobility Spectrometry (IMS) is a widely used and 'well-known' technique of ion separation in the gaseous phase based on the differences in ion mobilities under an electric field. All IMS instruments operate with an electric field that provides space separation, but some IMS instruments also operate with a drift gas flow that provides also a temporal separation. In this review we will summarize the current IMS instrumentation. IMS techniques have received an increased interest as new instrumentation and have become available to be coupled with mass spectrometry (MS). For each of the eight types of IMS instruments reviewed it is mentioned whether they can be hyphenated with MS and whether they are commercially available. Finally, out of the described devices, the six most-consolidated ones are compared. The current review article is followed by a companion review article which details the IMS hyphenated techniques (mainly gas chromatography and mass spectrometry) and the factors that make the data from an IMS device change as a function of device parameters and sampling conditions. These reviews will provide the reader with an insightful view of the main characteristics and aspects of the IMS technique.

Review on ion mobility spectrometry. Part 2: hyphenated methods and effects of experimental parameters.

Ion Mobility Spectrometry (IMS) is a widely used and 'well-known' technique of ion separation in the gaseous phase based on the differences of ion mobilities under an electric field. This technique has received increased interest over the last several decades as evidenced by the pace and advances of new IMS devices available. In this review we explore the hyphenated techniques that are used with IMS, specifically mass spectrometry as an identification approach and a multi-capillary column as a pre-separation approach. Also, we will pay special attention to the key figures of merit of the ion mobility spectrum and how data sets are treated, and the influences of the experimental parameters on both conventional drift time IMS (DTIMS) and miniaturized IMS also known as high Field Asymmetric IMS (FAIMS) in the planar configuration. The present review article is preceded by a companion review article which details the current instrumentation and contains the sections that configure both conventional DTIMS and FAIMS devices. These reviews will give the reader an insightful view of the main characteristics and aspects of the IMS technique.

[Glucose metabolism alterations and follow-up study of a non-diabetic adult population]. / Alteraciones del metabolismo de la glucosa y estudio de seguimiento de una población adulta no diabética.

OBJECTIVE: To determine the appearance of type 2 diabetes mellitus (DM2) and impaired fasting glucose (IFG) at five years of follow-up in a known non-diabetic population. DESIGN: nested case control studies (case s-control into a cohort) developed in two stages: 1) identification and characterization of the cohort and 2) follow-up. STUDY POPULATION: representative sample of a non-diabetic population between 40 and 75 years old attended in a Primary Health Center. IDENTIFICATION: 326 persons, 2.1% of whom were diagnosed of previously unknown DM2 and 7.3% of IFG. Insulin resistance (IR) was higher in patients with IFG and pancreatic function of beta cells (PFBC) was higher in the population without glucose metabolism alteration. FOLLOW-UP: 121 persons, 9.7 % of whom evolved to DM2 (all with IFG). IFG proportion at the end of the follow-up was 23.96%. CONCLUSIONS: At 5 years of follow-up, more than 1/3 of the population studied developed DM2 or IFG. These diagnoses were related with IR and PFBC.

Alteraciones del metabolismo de la glucosa y estudio de seguimiento de una población adulta no diabética / Glucose metabolism alterations and follow-up study of a non-diabetic adult population

Objetivo. Determinar la aparición de diabetes mellitus (DM) y glucemia basal alterada (GBA) a los cinco años de seguimiento de una población no diabética conocida. Material y métodos. Diseño: estudio casos-control anidado (casos-control dentro de una cohorte) desarrollado en dos fases, la de identificación y caracterización de la cohorte a estudio y la de seguimiento. Población a estudio: muestra representativa de población no diabética de 40 a 75 años atendida en un Centro de Atención Primaria. Resultados. Fase de identificación: 326 personas de las que un 2,1% fueron diagnosticadas de DM2 no conocida previamente y un 7,3% de GBA. La resistencia a la insulina (RI) fue superior en los pacientes con GBA y la función de la célula beta pancreática (FBP) fue superior en la población sin alteraciones del metabolismo de la glucosa. Fase de seguimiento: 121 personas. Un 9,7% evolucionaron a DM2 (todos con GBA previa) siendo la proporción de GBA al final del seguimiento de 23,96%. Conclusiones. A los cinco años de seguimiento, más de un tercio de la población estudiada evolucionó a DM o a GBA, estando la aparición de estas alteraciones relacionada con la RI y con la FBP (AU)

Objective. To determine the appearance of type 2 diabetes mellitus (DM2) and impaired fasting glucose (IFG) at five years of follow-up in a known non-diabetic population. Patients and methods. Design: nested case control studies (case s-control into a cohort) developed in two stages: 1) identification and characterization of the cohort and 2) follow-up. Study population: representative sample of a non-diabetic population between 40 and 75 years old attended in a Primary Health Center. Results. Identification: 326 persons, 2.1% of whom were diagnosed of previously unknown DM2 and 7.3% of IFG. Insulin resistance (IR) was higher in patients with IFG and pancreatic function of beta cells (PFBC) was higher in the population without glucose metabolism alteration. Follow-up: 121 persons, 9.7 % of whom evolved to DM2 (all with IFG). IFG proportion at the end of the follow-up was 23.96%. Conclusions. At 5 years of follow-up, more than 1/3 of the population studied developed DM2 or IFG. These diagnoses were related with IR and PFBC (AU)

Thermal AFM: a thermopile case study.

In this work, an atomic force microscope (AFM) with an integrated thermal sensor has been used to obtain the local spatial distribution of temperatures in a micromachined thermopile with submicron resolution. In this communication, we will show how the dimensional, structural and functional characteristics of a thermopile suits well with the requirements for AFM thermal imaging, and how a deeper insight of the thermopile operation can be gained with the aid of these advanced scanning probe-based tools.

[Socio-demographic and clinical characteristics of a patient population with diabetes mellitus]. / Características sociodemográficas y clínicas de una población de pacientes con diabetes mellitus.

OBJECTIVES: To describe sociodemographic and clinical characteristics of a diabetic population. To relate sociodemographic and clinical evolutionaries variables. DESIGN: Descriptive transversal study. SETTING: Three urban Primary Health Centers (PHC). Participants. Diabetic patients attended in these PHC.Measurements. VARIABLES: sociodemographic and clinical through an individualized survey and a medical record review. RESULTS: 1495 patients were studied from whom 96% were diabetic type 2. Age: 66 years old (SD 12). Sex: 56% were women. Education level: 62 didn't have finished their primary studies. Family: 71% live together with a partner. Years of evolution: Diabetes (DM) < 10 years: 47% in type 1; 64% in type 2. RISK FACTORS: DM 1: smokers 40%; hypertension (HTA) 7%; DM 2: smokers 12%; HTA 51%; obesity 26%; hypercholesterolemia 28%; hypertriglyceridemia 17%. Chronic complications: DM 1: retinopathy (DR) 26%; nephropathy (Nf) 3.5%; ischemic heart disease (IHD) 3.5%; periferic arteriopathy (PA) 7%; Cerebrovascular accident (CVA) 2%; peripheric neuropathy (PN) 5%. DM 2: DR 14%; Nf 13%; IHD 12%; PA 9%; CVA 5%; PN 4%; autonomic neuropathy 3%. Metabolic control DM 2: 67% HbA1c 7.5. Best metabolic control in DM with less years of evolution (p = 0.001). Treatment DM 2: 32% diet, 51% oral treatment, 13% insulin, 4% mixed. No relation with cultural level and family situation with metabolic control. In chronic complications only DR were more prevalent in patients with less cultural level (p = 0.037). CONCLUSIONS: Less cultural level doesn't influence neither metabolic control nor appearance chronic complications, except DR. The knowledge of diabetic population attended has allowed to detect the need of reinforce the intervention for decrease smoking and increase chronic complications detection.

Características sociodemográficas y clínicas de una población de pacientes con diabetes mellitus / Sociodemographic and clinical characteristics of a patient population with diabetes mellitus

Objetivo. Describir las características sociodemográficas y clínicas de una población diabética. Relacionar variables sociodemográficas y clinicoevolutivas. Diseño. Estudio descriptivo transversal. Emplazamiento. Tres áreas básicas de salud (ABS) urbanas. Pacientes diabéticos atendidos en estas ABS. Mediciones principales. Variables sociodemográficas y clínicas a través de encuesta individualizada y revisión de historias clínicas. Resultados. Se estudiaron 1.495 pacientes, 96 por ciento diabetes (DM) tipo 2. Edad: 66 años (DE ñ 12). Sexo: 56 por ciento mujeres. Estudios: 62 por ciento sin estudios primarios finalizados (15,5 por ciento analfabetismo, 46 por ciento primaria incompleta); 27 por ciento graduado escolar. Núcleo familiar: 71 por ciento convivía en pareja, 11 por ciento con los hijos, 12 por ciento vivían solos. Años evolución: DM < 10 años: 47 por ciento en DM 1; 64 por ciento en DM 2. Factores riesgo: DM 1: tabaquismo 40 por ciento; hipertensión arterial (HTA) 7 por ciento. DM 2: tabaquismo 12 por ciento; HTA 51 por ciento; obesidad 26 por ciento; hipercolesterolemia 28 por ciento; hipertrigliceridemia 17 por ciento. Complicaciones crónicas: DM 1: retinopatía (RD) 26 por ciento; nefropatía (Nf ) 3,5 por ciento; cardiopatía isquémica (CI) 3,5 por ciento; arteriopatía periférica (AP) 7 por ciento; accidente vascular cerebral (AVC) 2 por ciento; neuropatía periférica (NP) 5 por ciento. DM 2: RD 14 por ciento; Nf 13 por ciento; CI 12 por ciento; AP 9 por ciento; AVC 5 por ciento; NP 4 por ciento; neuropatía autonómica 3 por ciento. Control metabólico DM 2: 67 por ciento HbA1c 7,5. Mejor control metabólico en DM de menos años de evolución (p = 0,001). Tratamiento DM 2: 32 por ciento dieta, 51 por ciento tratamiento oral, 13 por ciento insulina, 4 por ciento mixto. No relación ni del nivel cultural ni de la situación familiar de los pacientes con el control metabólico de la DM. De las complicaciones crónicas, solamente la RD era más prevalente en pacientes con nivel cultural más bajo (p = 0,037).Conclusiones. El bajo nivel cultural de los pacientes no influye ni en el control metabólico ni en la aparición de complicaciones crónicas, a excepción de la RD. El conocimiento de la población diabética atendida ha permitido detectar la necesidad de reforzar intervenciones encaminadas a disminuir el tabaquismo y aumentar la detección de complicaciones crónicas (AU)