Preparation and characterization of ibuprofen solid lipid nanoparticles with enhanced solubility

Solid lipid nanoparticles (SLNs) loaded with ibuprofen (IBU) were prepared by solvent-free high-pressure homogenization (HPH). The produced SLNs consisted of stearic acid, triluarin or tripalmitin as lipid matrixes and various stabilizers. The produced empty and IBU-loaded SLNs were characterized for particle size stability over 8 months. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were implemented to characterize the IBU state of freeze-dried SLNs. IBU was found to be in both amorphous and crystalline form within the lipid matrix. The lyophilized powders showed increased dissolution rates for IBU depending on the lipid nature. SLNs were incubated in Caco-2 cells for 24?h showing negligible cell cytotoxicity up to 15?mg/mL.     

Effect of an all-trans-retinoic acid conjugate with spermine on viability of human prostate cancer and endothelial cells in vitro and angiogenesis in vivo

Retinoids constitute a family of organic compounds that are being used for the treatment of various diseases, ranging from acne vulgaris to acute promyelocytic leukemia. Their use however is limited due to serious adverse effects and there is a great need for analogues with better safety profile. In the present work, the effect of N¹,N¹²-bis(all-trans-retinoyl)spermine (RASP), a conjugate of all-trans-retinoic acid (atRA) with spermine, on angiogenesis in vivo and viability of human endothelial and prostate cancer cells in vitro were studied. Both atRA and RASP dose-dependently inhibited angiogenesis in the chicken embryo chorioallantoic membrane model. RASP was more effective and could be used in a wider dose range due to lower toxicity compared with atRA. Both retinoids decreased the number of human umbilical vein endothelial and prostate cancer LNCaP and PC3 cells in a concentration-dependent manner. RASP was more effective and potent compared with atRA, spermine, their combination, or conjugates of spermine with other acidic retinoids and/or psoralens in prostate cancer cells. The inhibitory effect of both atRA and RASP seems to be related to an increase of the tumour repressing gene retinoic acid receptor beta mRNA, was mediated by retinoic acid receptor alpha, and was proportional to endogenous retinoic acid receptor beta expression. These data suggest that RASP is more effective than atRA in decreasing angiogenesis and prostate cancer cell growth and identify retinoic acid receptor alpha as the receptor through which it causes retinoic acid receptor beta up-regulation and decrease of prostate cancer cell growth.     

Structural hierarchy of biomimetic materials for tissue engineered vascular and orthopedic grafts

Gelatine gels and gelatine/elastin gels have been prepared to be used in tissue engineered vascular grafts. Optical microscopy and atomic force microscopy (AFM) revealed that the gelatine formed nanofibrils as in soft collagen tissues. The gelatine/elastin gels were nanocomposites with flat elastin nanodomains embedded in the gelatine matrix mimicking the structure of the tunica media in arteries. Gelatine/"hydroxyapatite" (HA) nanocomposites were prepared with the in situ production of "HA" in solution. AFM revealed "HA" solid nanoparticles of about 20 nm size embedded in the gelatine matrix, which formed a hierarchical structure similar to that of the collagen matrix in bone. The application of amagnetic field of 9.4 T resulted in the elongation and orientation of gelatine particles and orientation of gelatine microfibrils in a direction perpendicular to that of the magnetic field. (c) 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008.     

Distinct signalling pathways promote phagocytosis of bacteria, latex beads and lipopolysaccharide in medfly haemocytes

In insects, phagocytosis is an important innate immune response against pathogens and parasites, and several signal transduction pathways regulate this process. The focal adhesion kinase (FAK)/Src and mitogen activated protein kinase (MAPK) pathways are of central importance because their activation upon pathogen challenge regulates phagocytosis via haemocyte secretion and activation of the prophenoloxidase (proPO) cascade. The goal of this study was to explore further the mechanisms underlying the process of phagocytosis. In particular, in this report, we used flow cytometry, RNA interference, enzyme-linked immunosorbent assay, Western blot and immunoprecipitation analysis to demonstrate that (1) phagocytosis of bacteria (both Gram-negative and Gram-positive) is dependent on RGD-binding receptors, FAK/Src and MAPKs, (2) latex bead phagocytosis is RGD-binding-receptor-independent and dependent on FAK/Src and MAPKs, (3) lipopolysaccharide internalization is RGD-binding-receptor-independent and FAK/Src-independent but MAPK-dependent and (4) in unchallenged haemocytes in suspension, FAK, Src and extracellular signal-regulated kinase (ERK) signalling molecules participating in phagocytosis show both a functional and a physical association. Overall, this study has furthered knowledge of FAK/Src and MAPK signalling pathways in insect haemocyte immunity and has demonstrated that distinct signalling pathways regulate the phagocytic activity of biotic and abiotic components in insect haemocytes. Evidently, the basic phagocytic signalling pathways among insects and mammals appear to have remained unchanged during evolution.     

Posterior cerebral artery dissection after excessive caffeine consumption in a teenager

Arterial ischemic stroke is a rare but significant cause of neurological deficits in childhood. Even though there is a variety of risk factors, identifying the etiology can sometimes be a hard diagnostic challenge. Arteriopathies in general, and more specifically, arterial dissection is one of the uncommon pathologies that can cause incidents of pediatric stroke. We report a rare case of a young adolescent with posterior cerebral artery dissection after excessive consumption of caffeine, contained in energy drinks, only hours before the onset of neurological symptoms. A complete neuroimaging evaluation (MRI, intracranial US and digital subtraction angiography) at the admission and during the follow-ups supported the diagnosis of arterial dissection possibly caused by caffeine overconsumption.     

The role of sleep endoscopy in oral appliance therapy for obstructive sleep apnea

ObjectiveAlthough oral appliance therapy is considered a validated treatment for obstructive sleep apnea, its therapeutic success varies significantly among patients. Drug-induced sleep endoscopy is often employed in order to identify candidates for upper airway surgery; however, it remains unknown whether its findings can be associated with success of oral appliance therapy. This study tested the hypothesis that drug-induced sleep endoscopy variables can predict the outcome of oral appliance therapy in obstructive sleep apnea patients.MethodsForty-nine obstructive sleep apnea patients [45 men; mean apnea-hypopnea index 25.3 ± 7.5 events/h; mean body mass index 28.2 ± 3.0 kg/m²] underwent drug-induced sleep endoscopy, followed by a one-month of oral appliance therapy, and subsequently a follow-up polysomnography to assess outcome.ResultsThirty-three patients (67.3%) were responders and sixteen were non-responders (32.6%). Non-responders had a higher occurrence of complete or partial circumferential collapse at velum in comparison with responders. Multivariate logistic regression analysis revealed that, among baseline clinical and polysomnographic characteristics and sleep endoscopy findings, the presence of complete circumferential collapse at velum and increased body mass index were the only independent predictors of oral appliance therapy failure.ConclusionDrug-induced sleep endoscopy can be used to predict a higher likelihood of success to oral appliance therapy in obstructive sleep apnea patients.     

Association of adherence to the Mediterranean diet and physical activity habits with the presence of insomnia in patients with obstructive sleep apnea

Sleep and Breathing - Insomnia and obstructive sleep apnea (OSA) are among the most prevalent sleep disorders and frequently co-occur, defining the sleep apnea-insomnia syndrome. However,...     

Is a Simple Food-Diverting Operation the Solution for Type 2 Diabetes Treatment? Experimental Study in a Non-Obese Rat Model

Background

The feasibility of a side-to-side jejunoileal anastomosis (SJA) to control type 2 diabetes mellitus (T2DM) was studied in non-obese diabetic Goto–Kakizaki (GK) rats.

Methods

Seventeen 14-week-old male GK rats were divided into three groups: SJA bypassing 60 % of the small bowel length, sham-operated jejunoileal bypass (Sham group), and control animals. Rats were observed for 10 weeks after surgery. Fasting blood glucose (FBG) levels and oral glucose tolerance test (OGTT) were measured before and after the procedure.

Results

Animals with SJA exhibited normalization of FBG levels from the 1st and up to the 10th postoperative week when the experiment terminated. OGTT compared with sham-operated and control groups was also significantly better at 3 and 8 weeks postoperatively.

Conclusions

A simple SJA, diverting the food and biliopancreatic secretion to the distal small bowel, was able to normalize both FBG levels and OGTT in a non-obese diabetic rat model.

     

Pharmaceutical Cognitive Enhancement in Greek University Students: Differences Between Users and Non-Users in Social Cognitive Variables,Burnout, and Engagement

Pharmaceutical cognitive enhancement (PCE) represents the non-medical use of prescribed medication for the improvement of cognitive functioning and academic performance. Although there are some studies about PCE prevalence, it is less clear how users and non-users of PCE substances differ with respect to their positive and negative student experiences (e.g. academic burnout and engagement with studies) and in social cognitive variables that relate to decision-making and self-regulation of PCE use. The present study assessed whether students with different experiences of PCE substance use displayed differences in academic burnout, study engagement, and social cognitive variables relevant to PCE use. Three hundred and forty-seven university students (mean age (M) = 22.15 years, SD = 1.69; 54% females) completed a battery of anonymous questionnaires on academic burnout, engagement with studies, social cognitive variables relevant to PCE use, and self-reported use of PCE substances and non-prescribed nutritional supplements. Three user groups emerged, namely non-users (51.9%, n = 180), single users of non-prescribed dietary supplements (25.4%, n = 88), and dual users of both non-prescribed dietary supplements and PCE (22.8%, n = 79). Multivariate analysis of variance indicated significant differences among the three user groups in intentions, attitudes, social norms, and anticipated regret toward PCE use. No significant differences were observed with respect to academic burnout and work engagement. The findings show that university students may engage in PCE use independent of their student experiences. Rather, a chemically assisted performance enhancement mindset seems to differentiate users from non-users of PCE substances.