Vitamin D loaded into lipid nanoparticles shows insulinotropic effect in INS-1E cells.

Increasing evidence suggests a beneficial role of vitamin D (VitD) supplementation in addressing the widespread VitD deficiency, but currently used VitD3 formulations present low bioavailability and toxicity constrains. Hence, poly(L-lactide-co-glycolide) (PLGA) nanoparticles (NPs), solid-lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were investigated to circumvent these issues. PLGA NPs prepared by emulsification or nanoprecipitation presented 74 or 200 nm, and association efficiency (AE) of 68 % and 17 %, respectively, and a rapid burst release of VitD3. Both SLN and NLCs presented higher polydispersity and larger NPs size, around 500 nm, which could be reduced to around 200 nm by use of hot high-pressure homogenization in the case of NLCs. VitD3 was efficiently loaded in both SLNs and NLCs with an AE of 82 and 99 %, respectively. While SLNs showed burst release, NLCs allowed a sustained release of VitD3 for nearly one month. Furthermore, NLCs showed high stability with maintenance of VitD3 loading for up to one month at 4 °C and no cytotoxic effects on INS-1E cells up to 72 h. A trending increase (around 30 %) on glucose-dependent insulin secretion was observed by INS-1E cells pre-treated with VitD3. This effect was consistently observed in the free form and after loading on NLCs. Overall, this work contributed to further elucidation on a suitable delivery system for VitD3 and on the effects of this metabolite on ß cell function.

High-definition blood flow imaging improves quantification of left ventricular volumes and ejection fraction.

AIMS: The accuracy and reproducibility of echocardiography to quantify left ventricular ejection fraction (LVEF) is limited due to image quality. High-definition blood flow imaging is a new technique which improves cavity delineation without the need for medication or intravenous access. We sought to examine the impact of high-definition blood flow imaging on accuracy and reproducibility of LV systolic function assessment. METHODS AND RESULTS: Prospective observational study of consecutive patients undergoing 2D and 3D transthoracic echocardiography (TTE), high-definition blood flow imaging, and cardiac magnetic resonance (CMR) within 1 h of each other. Left ventricular systolic function characterized by left ventricular end-systolic volumes and left ventricular end-diastolic volumes and LVEF were measured. Seventy-six patients were included. Correlation of 2D TTE with CMR was modest (r = 0.68) with a worse correlation in patients with three or more segments not visualized (r = 0.58). High-definition blood flow imaging was feasible in all patients, and the correlation of LVEF with CMR was excellent (r = 0.88). The differences between 2D, high-definition blood flow, and 3D TTE compared to CMR were 5 ± 9%, 2 ± 5%, and 1 ± 3%, respectively. The proportion of patients where the grade of LV function was correctly classified improved from 72.3% using 2D TTE to 92.8% using high-definition blood flow imaging. 3D TTE also had excellent correlation with CMR (r = 0.97) however was only feasible in 72.4% of patients. CONCLUSION: High-definition blood flow imaging is highly feasible and significantly improves the diagnostic accuracy and grading of LV function compared to 2D echocardiography.

Targeting ß Cells with Cathelicidin Nanomedicines Improves Insulin Function and Pancreas Regeneration in Type 1 Diabetic Rats.

Type 1 diabetes (T1D) is an incurable condition with an increasing incidence worldwide, in which the hallmark is the autoimmune destruction of pancreatic insulin-producing ß cells. Cathelicidin-based peptides have been shown to improve ß cell function and neogenesis and may thus be relevant while developing T1D therapeutics. In this work, a cathelicidin-derived peptide, LLKKK18, was loaded in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), surface-functionalized with exenatide toward a GLP-1 receptor, aiming the ß cell-targeted delivery of the peptide. The NPs present a mean size of around 100 nm and showed long-term stability, narrow size distribution, and negative ζ-potential (-10 mV). The LLKKK18 association efficiency and loading were 62 and 2.9%, respectively, presenting slow and sustained in vitro release under simulated physiologic fluids. Glucose-stimulated insulin release in the INS-1E cell line was observed in the presence of the peptide. In addition, NPs showed a strong association with ß cells from isolated rat islets. After administration to diabetic rats, NPs induced a significant reduction of the hyperglycemic state, an improvement in the pancreatic insulin content, and glucose tolerance. Also remarkable, a considerable increase in the ß cell mass in the pancreas was observed. Overall, this novel and versatile nanomedicine showed glucoregulatory ability and can pave the way for the development of a new generation of therapeutic approaches for T1D treatment.

Innovative Aqueous Nanoemulsion Prepared by Phase Inversion Emulsification with Exceptional Homogeneity.

Formulating low-solubility or low-permeability drugs is a challenge, particularly with the low administration volumes required in intranasal drug delivery. Nanoemulsions (NE) can solve both issues, but their production and physical stability can be challenging, particularly when a high proportion of lipids is necessary. Hence, the aim of the present work was to develop a NE with good solubilization capacity for lipophilic drugs like simvastatin and able to promote the absorption of drugs with low permeability like fosphenytoin. Compositions with high proportion of two lipids were screened and characterized. Surprisingly, one of the compositions did not require high energy methods for high droplet size homogeneity. To better understand formulation factors important for this feature, several related compositions were evaluated, and their relative cytotoxicity was screened. Optimized compositions contained a high proportion of propylene glycol monocaprylate NF, formed very homogenous NE using a low-energy phase inversion method, solubilized simvastatin at high drug strength, and promoted a faster intranasal absorption of the hydrophilic prodrug fosphenytoin. Hence, a new highly homogeneous NE obtained by a simple low-energy method was successfully developed, which is a potential alternative for industrial application for the solubilization and protection of lipophilic actives, as well as (co-)administration of hydrophilic molecules.

Cellulose/Salep-based intelligent aerogel with red grape anthocyanins: Preparation, characterization and application in beef packaging.

The purpose of this study was to prepare a porous intelligent aerogel for food packaging applications, in particular for monitoring minced beef freshness, using cellulose extracted from grape stalk, Salep as a copolymer, and red grape anthocyanins as a pH-sensitive pigment. Aerogels based on cellulose 1% (w/v) and Salep 1% (w/v) at ratios of 1:3, 3:1, and 1:1 were prepared by lyophilization. Aerogel with high porosity, low density, and higher mean pore size was chosen for preparing intelligent colorimetric aerogel (ICA) with the addition of 0.44 mg/100 mL of anthocyanins. Based on the color parameters, the stability of ICA was satisfactory when exposed to both light and dark conditions, as well as when stored at either 4 or 25 °C. Additionally, X-ray diffraction and thermogravimetric analyses indicated that an amorphous aerogel was formed, with a thermal decomposition temperature of 320 °C. The color of the ICA changed from purple on the first and 3rd days of packaging to blue-gray on the 6th day. As the spoilage process continued, the color of the indicator became dark brown. Taken together, ICA showed a quick response to minced beef spoilage with the ability to differentiate between fresh and spoiled meat during storage at 4 °C.

Exercise Oscillatory Ventilation Improves Heart Failure Prognostic Scores.

BACKGROUND: Several heart failure (HF) prognostic risk scores are available to guide the ideal time for listing candidates for a heart transplant (HTx). The detection of exercise oscillatory ventilation (EOV) during cardiopulmonary exercise testing (CPET) is associated with advanced HF and a worse prognosis, and yet it is not accounted for in these risk scores. Therefore, this study aimed to assess whether EOV further adds prognostic value to HF scores. METHODS: A single-centre retrospective cohort study was undertaken of consecutive HF patients with reduced ejection fraction (HFrEF) who underwent CPET from 1996 to 2018. The Heart Failure Survival Score (HFSS), Seattle Heart Failure Model (SHFM), Meta-analysis Global Group In Chronic Heart Failure (MAGGIC), and Metabolic Exercise Cardiac Kidney Index (MECKI) were calculated. The added value of EOV on top of those scores was assessed using a Cox proportional hazard model. The added discriminative power was also assessed by receiver operating characteristic curve comparison. RESULTS: A total of 390 HF patients with a median age of 58 (IQR 50-65) years were investigated, of whom 78% were male and 54% had ischaemic heart disease. The median peak oxygen consumption was 15.7 mL/kg/min (IQR 12.8-20.1). Exercise oscillatory ventilation was detected in 153 (39.2%) patients. Over a median follow-up of 2 years, 61 patients died (49 due to a cardiovascular reason) and 54 had a HTx. Exercise oscillatory ventilation independently predicted the composite outcome of all-cause death and HTx. Furthermore, the presence of this ventilatory pattern significantly improved the prognostic performance of both HFSS and MAGGIC scores. CONCLUSION: Exercise oscillatory ventilation was often found in a cohort of HF patients with reduced LVEF who underwent CPET. It was found that EOV added further prognostic value to contemporary HF scores, suggesting that this easily obtained parameter should be included in future modified HF scores.

Myocardial Evaluation in Patients with Aortic Stenosis by Cardiac Computed Tomography.

BACKGROUND: Aortic valve stenosis (AVS) is one of the most prevalent pathologies affecting the heart that can curtail expected survival and quality of life if not managed appropriately. CURRENT STATUS: Cardiac computed tomography (CT) has long played a central role in this subset, mostly for severity assessment and for procedural planning. Although not as widely accepted as other imaging modalities for functional myocardial assessment [i. e., transthoracic echocardiogram (TTE), cardiac magnetic resonance (CMR)], this technique has recently increased its clinical application in this regard. FUTURE OUTLOOK: The ability to provide morphological, functional, tissue, and preprocedural information highlights the potential of the "all-in-one" concept of cardiac CT as a potential reality for the near future for AVS assessment. In this review article, we sought to analyze the current applications of cardiac CT that allow a full comprehensive evaluation of aortic valve disease. KEY POINTS: · Noninvasive myocardial tissue characterization stopped being an exclusive feature of cardiac magnetic resonance.. · Emerging acquisition methods make cardiac CT an accurate and widely accessible imaging modality.. · Cardiac CT has the potential to become a "one-stop" exam for comprehensive aortic stenosis assessment.. CITATION FORMAT: · Gama FF, Patel K, Bennett J et al. Myocardial Evaluation in Patients with Aortic Stenosis by Cardiac Computed Tomography. Fortschr Röntgenstr 2023; 195: 506 - 513.

Breaking-Up Sedentary Behavior and Detraining Effects on Glycemic Control: A Randomized Crossover Trial in Trained Older Adults.

In a randomized crossover trial, we examined the effects of interrupting sedentary behavior on glycemic control in trained older adults, before and after 2 weeks of detraining. Fourteen participants (65-90 years old) completed two 7-hr conditions before and after 2 weeks of detraining: (a) uninterrupted sitting (SIT) and (b) sitting plus 2 min of moderate-intensity activity every 30 min (INT). Both before and after detraining, no differences were observed for 7-hr glucose area under the curve (7 hr AUC) and mean glucose between sitting plus 2 min of moderate-intensity activity and uninterrupted sitting conditions. After detraining and for the SIT condition, higher values of 7-hr AUC (p = .014) and mean glucose (p = .015) were observed, indicating worsened glycemic control. No changes were observed in INT condition between both time points. Frequent interruptions in sedentary behavior had no effect on glycemic control, prior to or after detraining. Even so, older adults experiencing a short-term detraining period should avoid prolonged bouts of sedentary behavior that may jeopardize their glycemic control.