SGLT2 inhibitors and diabetic ketoacidosis: data from the FDA Adverse Event Reporting System

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are indicated for the treatment of type 2 diabetes and may also improve glucose control in type 1 diabetes. In 2015, regulatory agencies warned that SGLT2i may favour diabetic ketoacidosis (DKA). We provide a detailed analysis of DKA reports in which an SGLT2i was listed among suspect or concomitant drugs in the US Food and Drug Administration Adverse Event Reporting System (FAERS)

Impact of the Number of Needle Tip Bevels on the Exerted Forces and Energy in Insulin Pen Injections

Patients affected with type 1 diabetes and a non-negligible number of patients with type 2 diabetes are insulin dependent. Both the injection technique and the choice of the most suitable needle are fundamental for allowing them to have a good injection experience. The needles may differ in several parameters, from the length and diameter, up to the forces required to perform the injection and to some geometrical parameters of the needle tip (e.g., number of facets or bevels). The aim of the research is to investigate whether an increased number of bevels could decrease forces and energy involved in the insertion–extraction cycle, thus potentially allowing patients to experience lower pain. Two needle variants, namely, 31 G 5 mm and 32 G 4 mm, are considered, and experimental tests are carried out to compare 3-bevels with 5-bevels needles for both the variants. The analysis of the forces and energy for both variants show that the needles with 5 bevels require a statistically significant lower drag or sliding force (p-value = 0.040 for the 31 G 5 mm needle and p-value < 0.001 for 32 G 4 mm), extraction force (p-value < 0.001 for both variants), and energy (p-value < 0.001 for both variants) during the insertion–extraction cycle. As a result, 3-bevels needles do not have the same functionality of 5-bevels needles, show lower capacity of drag and extraction, and can potentially be related to more painful injection experience for patients

Multimeric, Multifunctional Derivatives of Poly(ethylene glycol)

Abstract: This article reviews the use of multifunctional polymers founded on high-molecular weight poly(ethylene glycol) (PEG). The design of new PEG derivatives assembled in a dendrimer-like multimeric fashion or bearing different functionalities on the same molecule is described. Their use as new drug delivery systems based on the conjugation of multiple copies or diversely active drugs on the same biocompatible support is illustrated. Keywords: poly(ethylene glycol); multifunctional polymers; conjugation; drug delivery 1. Introduction For the application of biopharmaceuticals in human therapy, the covalent coupling of poly(ethylene glycol) (PEG) chains to drugs, or PEGylation, has been an outstanding innovation. Important pioneering work in this field was performed by Davis and Abuchowski, laying the cornerstone for the commercial success of this technology [1]. Even though many attempts have been undertaken to develop new polymers with improved properties, none of these new substances have been able to compete with poly(ethylene glycol) for this application. This can be explained by the biocompatibility of PEG and the good experience with PEG as a low-cost additive for the pharmaceutical and cosmetic industry over the last decades. An ideal PEG reagent fulfills at least the following criteria: (a)

Una nuova sfida per linagliptin: diabete, trapianto d'organo e insufficienza renale cronica nel medesimo paziente

The association between liver cirrhosis and type 2 diabetes mellitus (DMT2) has been known for many years. It is estimated that changes in glucose metabolism are present in at least two thirds of cirrhosis patients. Diabetes can be both a consequence of liver disease and a pre-existing condition. In the first case, liver transplantation would be the solution but post-transplant diabetes remains a common condition. For patients with liver cirrhosis the therapeutic approach for the treatment of DMT2 is extremely limited and the studies available on this type of population are very few. The pharmacokinetic characteristics of linagliptin are well suited for patients with DMT2 and chronic liver disease; in fact, no dose adjustment is required in patients regardless of the degree of hepatic impairment. With regard to the treatment of diabetes in post-transplantation, data on the efficacy and safety of oral hypoglycemic drugs are scarce; however, the available studies suggest that dipeptidyl peptidase 4 (DPP4i) inhibitors are safe and effective in these patients. In describing this clinical case, we discuss how the use of a DPP4i, and in particular of linagliptin, may represent a valid therapeutic strategy in the management of diabetic, cirrhotic patients who undergo liver transplantation (Diabetology)

Divergences in insulin resistance between the different phenotypes of the polycystic ovary syndrome

Context/Objective: Current diagnostic criteria for polycystic ovary syndrome (PCOS) have generated distinct PCOS phenotypes, based on the different combinations of diagnostic features found in each patient. Our aim was to assess whether either each single diagnostic feature or their combinations into the PCOS phenotypes may predict insulin resistance in these women. Patients/Design: A total of 137 consecutive Caucasian women with PCOS, diagnosed by the Rotterdam criteria, underwent accurate assessment of diagnostic and metabolic features. Insulin sensitivity was measured by the glucose clamp technique. Results: Among women with PCOS, 84.7% had hyperandrogenism, 84.7% had chronic oligoanovulation, and 89% had polycystic ovaries. According to the individual combinations of these features, 69.4% of women had the classic phenotype, 15.3% had the ovulatory phenotype, and 15.3% had the normoandrogenic phenotype. Most subjects (71.4%) were insulin resistant. However, insulin resistance frequency differed among phenotypes, being 80.4%, 65.0%, and 38.1%, respectively, in the 3 subgroups (P < .001). Although none of the PCOS diagnostic features per se was associated with the impairment in insulin action, after adjustment for covariates, the classic phenotype and, to a lesser extent, the ovulatory phenotype were independently associated with insulin resistance, whereas the normoandrogenic phenotype was not. Metabolic syndrome frequency was also different among phenotypes (P = .030). Conclusions: There is a scale of metabolic risk among women with PCOS. Although no single diagnostic features of PCOS are independently associated with insulin resistance, their combinations, which define PCOS phenotypes, may allow physicians to establish which women should undergo metabolic screening. In metabolic terms, women belonging to the normoandrogenic phenotype behave as a separate group

Ecosistemi per la ricerca Atti Convegno ACNP/NILDE. Trieste, 22-23 maggio 2014

Il secondo convegno congiunto ACNP / NILDE: ecosistemi per la ricerca è stato ospitato dal 22 al 23 maggio 2014 dall’Università di Trieste. Sono stati affrontati in un’ottica internazionale i temi del rapporto tra cataloghi collettivi e servizi interbibliotecari, e il più generale ambito dei servizi bibliografici per la ricerca scientifica. ACNP e NILDE possono essere considerati un vero e proprio ecosistema. Le biblioteche e i bibliotecari collaborano tra di loro in maniera reciproca e secondo modalità interconnesse, offrendo agli utenti servizi sempre più evoluti e dinamici. Questo ecosistema, essendo aperto, mette i propri servizi a disposizione della ricerca scientifica in senso generale. Il convegno di Trieste ha offerto l’occasione di investigare e proporre soluzioni innovative, interconnessioni e relazioni nuove e più proficue

Large-scale Solution Synthesis of Phosphorothioate Oligonucleotides: A Comparison of the Phosphoro-amidite and Phosphotriester Dimeric Approaches

Two different approaches to the solution synthesis of oligonucleotides are compared. Both procedures use dimer synthons as building blocks to save time and to improve the final product yield and quality. These strategies look quite promising due to their easy up-scaling, providing an advantageous alternative to the well-established solid-phase methods

Il rischio cardiovascolare e la concentrazione plasmatica del colesterolo LDL: il ruolo dei Servizi Sanitari Regionali

Cardiovascular risk and increased plasma LDL cholesterol concentration: the role of the Regional Health ServiceThe relevance of hypercholesterolemia, as a risk factor for cardiovascular (CV) disease, requires urgent actions to detect and assist high-risk citizens/patients, thus reducing and/or avoiding future complications. This goal could be achieved through more widespread awareness of the problem within the Health System of the Veneto Region, joint efforts between clinical laboratories and clinicians in transmitting and interpreting informative laboratory reports, and deeper integration of hospital and community health services. Data from recent studies, recommendations of scientific societies and political-institutional guidelines helped in determining the number of patients in the Veneto Region, which may be suffering from clinical or biochemical conditions that impact on CV risk. These include hypercholesterolemia, which is particularly addressed in this paper, with special emphasis on FH (familial hypercholesterolemia), a chronic disease associated with very high CV risk

Representaciones sobre querer ser /ser buen docente en el Profesorado de Inglés de la UNMdP

El presente trabajo se encuentra enmarcado en el Proyecto Estudiantes y docentes en contextos de formación III: indagación del proceso de construcción del conocimiento del Saber/Ser docente en el Profesorado de la Universidad Nacional de Mar del Plata a partir de narrativas, (auto) biografías y diarios reflexivos, del grupo GIIEFOD, radicado en el Centro de Investigaciones Multidisciplinarias en Educación de la Facultad de Humanidades. Consideramos que las historias escolares y las experiencias pedagógicas que relatan estudiantes del Profesorado en primera persona generan una fuente muy valiosa para conocer lo que hacen, piensan y sienten quienes habitan nuestra Universidad. Nuestro objetivo es entonces comprender cuáles son las representaciones de dos de las estudiantes del Profesorado de Inglés local que actuaron como participantes en nuestra investigación sobre querer ser / ser buen docente. A partir de las narrativas biográficas y diarios de reflexión de dichas participantes también se pretende indagar si sus biografías escolares han influenciado la construcción de dichas representaciones y si éstas inciden en cómo estas alumnas avanzadas piensan sus primeros pasos en la práctica docente