Adipose Tissue: A Novel Target of the Incretin Axis? A Paradigm Shift in Obesity-Linked Insulin Resistance.

Adipose tissue (AT) represents a plastic organ that can undergo significant remodeling in response to metabolic demands. With its numerous checkpoints, the incretin system seems to play a significant role in controlling glucose homeostasis and energy balance. The importance of the incretin hormones, namely the glucagon-like peptide-1 (GLP-1) and the glucose-dependent insulinotropic peptide (GIP), in controlling the function of adipose cells has been brought to light by recent studies.

Nutritional Management of Athletes with Type 1 Diabetes: A Narrative Review.

Type 1 diabetes mellitus (T1DM) represents a complex clinical challenge for health systems. The autoimmune destruction of pancreatic beta cells leads to a complete lack of insulin production, exposing people to a lifelong risk of acute (DKA, coma) and chronic complications (macro and microvascular). Physical activity (PA) has widely demonstrated its efficacy in helping diabetes treatment.

Diabetes-Alzheimer's connection in older age: SGLT2 inhibitors as promising modulators of disease pathways.

Late-onset Alzheimer's disease (LOAD) is the most frequent cause of dementia in older persons. Subjects affected by type 2 diabetes mellitus (T2DM) are at higher risk of vascular disease, cognitive decline, and dementia. LOAD has many characteristics shared with impaired insulin signaling pathways, and substantial evidence has demonstrated a pivotal role in dysregulated glucose metabolism in its pathogenesis.

The role of gastric emptying in glucose homeostasis and defense against hypoglycemia: Innocent bystander or partner in crime?

Maintenance of plasma glucose (PG) homeostasis is due to a complex network system. Even a minor fall in PG activates multiple neuroendocrine actions promoting hormonal, metabolic and behavioral responses, which prevent and ultimately recover hypoglycemia, primarily neuroglycopenia. Among these responses, gastric emptying (GE) plays an important role by coordinated mechanisms which regulate transit and absorption of nutrients through the small intestine.

Diurnal Cycling of Insulin Sensitivity in Type 2 Diabetes: Evidence for Deviation From Physiology at an Early Stage.

Unlabelled: The aim of this study was to establish the contribution of insulin resistance to the morning (a.m.) versus afternoon (p.

Bone Health Care Pathway for Non-metastatic Prostate Cancer Patients on Radiation and Androgen Deprivation Therapy.

Background/aim: Survival rates of prostate cancer (PCa) patients have improved considerably as a result of earlier diagnosis and therapies, including radiotherapy (RT) and androgen deprivation therapy (ADT). Patients on ADT develop cancer treatment-induced bone loss (CTIBL) and a high risk of fragility fractures. Bone health (BH) assessment is strongly recommended, together with timely initiation of treatments, to counteract CTIBL and preserve bone strength.

Adipose Tissue Plasticity in Response to Pathophysiological Cues: A Connecting Link between Obesity and Its Associated Comorbidities.

Adipose tissue (AT) is a remarkably plastic and active organ with functional pleiotropism and high remodeling capacity. Although the expansion of fat mass, by definition, represents the hallmark of obesity, the dysregulation of the adipose organ emerges as the forefront of the link between adiposity and its associated metabolic and cardiovascular complications. The dysfunctional fat displays distinct biological signatures, which include enlarged fat cells, low-grade inflammation, impaired redox homeostasis, and cellular senescence.

Glucagon as a Therapeutic Approach to Severe Hypoglycemia: After 100 Years, Is It Still the Antidote of Insulin?

Hypoglycemia represents a dark and tormented side of diabetes mellitus therapy. Patients treated with insulin or drug inducing hypoglycemia, consider hypoglycemia as a harmful element, which leads to their resistance and lack of acceptance of the pathology and relative therapies. Severe hypoglycemia, in itself, is a risk for patients and relatives.

Evaluation of self-emulsifying drug delivery systems for oral insulin delivery using an in vitro model simulating the intestinal proteolysis.

The gentle preparation and the functionalization potential of self-emulsifying drug delivery systems (SEDDS) make them an interesting formulation strategy for oral administration of peptide and protein (p/p) drugs. A series of Kolliphor® RH40 (RH40) and Labrasol® (LAB)-based SEDDS containing either long-chain (LC) or medium-chain (MC) glycerides were formulated and characterized with regard to their rheological behavior, as well as the size distribution and zeta potential of the generated emulsions. Insulin, in order to be incorporated in SEDDS, was complexed with soybean phosphatidylcholine.

Exploring the mucoadhesive behavior of sucrose acetate isobutyrate: a novel excipient for oral delivery of biopharmaceuticals.

Oral drug delivery is an attractive noninvasive alternative to injectables. However, oral delivery of biopharmaceuticals is highly challenging due to low stability during transit in the gastrointestinal tract (GIT), resulting in low systemic bioavailability. Thus, novel formulation strategies are essential to overcome this challenge.

Electrocardiography for diagnosis of left ventricular hypertrophy in hypertensive patients with atrial fibrillation.

Left ventricular (LV) hypertrophy at electrocardiography (ECG) predicts incident atrial fibrillation (AF). However, the diagnostic performance of ECG for diagnosis of LV hypertrophy in patients with AF is still not well characterized. We analyzed 563 hypertensive patients enrolled in the Umbria-Atrial Fibrillation (Umbria-FA) registry, an ongoing prospective observational registry in patients with AF.

Sudden Cardiac Death in Hypertensive Patients.

In patients with hypertension, but without established cardiovascular disease, predictive factors for sudden cardiac death (SCD) remain undefined. We followed for an average of 10.3 years a cohort of 3242 initially untreated hypertensive patients without evidence of coronary or cerebrovascular heart disease at entry.

SEDDS for intestinal absorption of insulin: Application of Caco-2 and Caco-2/HT29 co-culture monolayers and intra-jejunal instillation in rats.

To face the challenges of oral delivery of peptide and protein (P/P) drugs, self-emulsifying drug delivery systems (SEDDSs) containing monoacyl phosphatidylcholine (MAPC), Labrasol (LAB) and medium-chain (MC) monoglycerides as permeation enhancers (PEs) were evaluated for their effect on intestinal absorption of insulin. In this study, insulin was complexed with phosphatidylcholine (SPC) to form an insulin-SPC complex (ins-SPC) with increased lipophilicity. The following three SEDDSs: MCT(MAPC) (MC triglycerides and MAPC included), MCT(RH40) (MC triglycerides and Kolliphor RH40 included) and LCT(MAPC) (long-chain triglycerides and MAPC included) were loading with ins-SPC (4% or 8% w/w of SPC).

Temperature-Induced Self-Assembly of the Group B Streptococcus (GBS) Fusion Antigen GBS-NN.

Group B Streptococcus (GBS) is a leading cause of serious bacterial neonatal infections worldwide, which provides an unmet medical need for a globally effective vaccine. The recombinant GBS fusion antigen GBS-NN contains the N-terminal regions of the GBS Rib and Alpha C proteins. It shows promising immunogenicity eliciting protective immunity in mice and encouraging results in early human clinical trials.

Comparison of lipases for in vitro models of gastric digestion: lipolysis using two infant formulas as model substrates.

The aim of this study was to find a lipase suitable as a surrogate for Human Gastric Lipase (HGL), since the development of predictive gastrointestinal lipolysis models are hampered by the lack of a lipase with similar digestive properties as HGL. Three potential surrogates for HGL; Rhizopus Oryzae Lipase (ROL), Rabbit Gastric Lipase (RGL) and recombinant HGL (rHGL), were used to catalyze the in vitro digestion of two infant formulas (a medium-chain triacylglyceride enriched formula (MC-IF) and a predominantly long-chain triacylglyceride formula (LC-IF)). Digesta were withdrawn after 0, 5, 15, 30, 60 min of gastric digestion and after 90 or 180 min of intestinal digestion with or without the presence of pancreatic enzymes, respectively.

Dehydroepiandrosterone (DHEA) supplementation results in supraphysiologic DHEA-S serum levels and progesterone assay interference that may impact clinical management in IVF.

Purpose: Dehydroepiandrosterone (DHEA) is often prescribed for poor responders in IVF in an effort to improve response to ovarian stimulation. The effect of DHEA supplementation and resultant supraphysiologic DHEA-S serum levels on sex steroid assays has not been evaluated in this population. This study seeks to determine the relationship between DHEA supplementation and progesterone measurements to characterize the degree of interference with particular immunoassays.

Influence of Tableting on the Conformation and Thermal Stability of Trypsin as a Model Protein.

The objective of this study was to investigate the influence of compaction on the conformation of trypsin, its transition temperature (Tm ) of unfolding, and its folding reversibility after thermal denaturation. Plain trypsin was compacted at 40-382 MPa. Pressure-induced changes in the trypsin conformation and the extent of their reversibility were determined using solid- and liquid-state IR spectroscopy together with principal component analysis and an area overlap approach.

Characterization of particulate drug delivery systems for oral delivery of Peptide and protein drugs.

Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe biological membranes. To overcome these barriers, different formulation strategies for oral delivery of biomacromolecules have been proposed, including lipid based formulations and polymer-based particulate drug delivery systems (DDS).

Preparation and characterization of insulin-surfactant complexes for loading into lipid-based drug delivery systems.

Insulin suffers from poor oral bioavailability, but lipid-based drug delivery systems (DDS) may constitute promising tools for improving this. Loading of protein drugs into lipid matrices may, however, be challenging, and different formulation approaches must be taken to achieve sufficient loading and preservation of native structure. The aim of the present study was to characterize insulin after complexation with biocompatible surfactants to improve loading into lipid-based DDS.

[5 days Cefaclor vs. 10 days amoxicillin/clavulanate in the treatment of childhood streptococcal pharyngitis. Data from a randomized clinical trial].

Aim: The duration of therapy represents a fundamental aspect in the compliance to the therapy of child pathologies, such as pharyngotonsillitis, treated with oral therapy. Although penicillin and amoxicillin are the first choice antibiotics in the case of a child suffering from pharyngotonsillitis with the proven presence of Group A β-hemolytic Streptococcus (GAS), the number of orally administered doses and 10 days of therapy, considerably lower the compliance.

Methods: An open phase IV randomized multicenter clinical trial was conducted in parallel groups, involving 49 family pediatrician (FP), distributed over the entire national territory, enrolling 435 children suffering from GAS-FT.

Ionic strength-dependent denaturation of Thermomyces lanuginosus lipase induced by SDS.

Triglyceride lipase from Thermomyces lanuginosus (TlL) has been reported to be resistant to denaturation by sodium dodecyl sulfate (SDS). We have found that at neutral pH, structural integrity is strongly dependent on ionic strength. In 10mM phosphate buffer and SDS, the lipase exhibits a far-UV CD spectrum similar to other proteins denatured in this surfactant while the near-UV CD spectrum shows a complete loss of tertiary structure, observations supported by steady state fluorescence spectroscopy.

Influence of glycosylation on the adsorption of Thermomyces lanuginosus lipase to hydrophobic and hydrophilic surfaces.

In the pharmaceutical industry, protein drugs are modified by, for instance, glycosylation in order to obtain protein drugs with improved delivery profiles and/or increased stability. The effect of glycosylation on protein adsorption behaviour is one of the stability aspects that must be evaluated during development of glycosylated protein drug products. We have studied the effect of glycosylation on the adsorption behaviour of Thermomyces lanuginosus lipase to hydrophobic and hydrophilic surfaces using total internal reflection fluorescence, surface plasmon resonance, far-UV circular dichroism and fluorescence.

Regulation of dCTP deaminase from Escherichia coli by nonallosteric dTTP binding to an inactive form of the enzyme.

The trimeric dCTP deaminase produces dUTP that is hydrolysed to dUMP by the structurally closely related dUTPase. This pathway provides 70-80% of the total dUMP as a precursor for dTTP. Accordingly, dCTP deaminase is regulated by dTTP, which increases the substrate concentration for half-maximal activity and the cooperativity of dCTP saturation.