Intestinal mucosa permeability following oral insulin delivery using core shell corona nanolipoparticles

Chitosan nanoparticles (NC) have excellent capacity for protein entrapment, favorable epithelial permeability, and are regarded as promising nanocarriers for oral protein delivery. Herein, we designed and evaluated a class of core shell corona nanolipoparticles (CSC) to further improve the absorption through enhanced intestinal mucus penetration. CSC contains chitosan nanoparticles as a core component and pluronic F127-lipid vesicles as a shell with hydrophilic chain and polyethylene oxide PEO as a corona. These particles were developed by hydration of a dry pluronic F127-lipid film with NC suspensions followed by extrusion. Insulin nested inside CSC was well protected from enzymatic degradation. Compared with NC, CSC exhibited significantly higher efficiency of mucosal penetration and, consequently, higher cellular internalization of insulin in mucus secreting E12 cells. The cellular level of insulin after CSC treatment was 36-fold higher compared to treatment with free insulin, and 10-fold higher compared to NC. CSC significantly facilitated the permeation of insulin across the ileum epithelia, as demonstrated in an ex vivo study and an in vivo absorption study. CSC pharmacological studies in diabetic rats showed that the hypoglycemic effects of orally administrated CSC were 2.5-fold higher compared to NC. In conclusion, CSC is a promising oral protein delivery system to enhance the stability, intestinal mucosal permeability, and oral absorption of insulin.     

Clinical management of voice and breathing problems in two patients with vagus nerve stimulation therapy

We report two cases highlighting the diversity of vagal nerve stimulation (VNS)‐related effects on voice and breathing in patients with refractory epilepsy. The patients had both implantation and stimulation‐related side effects, which lasted for several months, impacting on their quality of life. The adverse effects appear to be due to recurrent laryngeal nerve paralysis‐related vocal cord hypofunction and stimulation‐related vocal fold spasms, however, their inter‐relationship is complex. In one of the patients, we were able to utilize the novel programming capabilities of the VNS device to reduce the laryngeal side effects without compromising therapeutic efficacy. [Published with video sequences].     

A gene network model accounting for development and evolution of mammalian teeth

Generation of morphological diversity remains a challenge for evolutionary biologists because it is unclear how an ultimately finite number of genes involved in initial pattern formation integrates with morphogenesis. Ideally, models used to search for the simplest developmental principles on how genes produce form should account for both developmental process and evolutionary change. Here we present a model reproducing the morphology of mammalian teeth by integrating experimental data on gene interactions and growth into a morphodynamic mechanism in which developing morphology has a causal role in patterning. The model predicts the course of tooth-shape development in different mammalian species and also reproduces key transitions in evolution. Furthermore, we reproduce the known expression patterns of several genes involved in tooth development and their dynamics over developmental time. Large morphological effects frequently can be achieved by small changes, according to this model, and similar morphologies can be produced by different changes. This finding may be consistent with why predicting the morphological outcomes of molecular experiments is challenging. Nevertheless, models incorporating morphology and gene activity show promise for linking genotypes to phenotypes.     

Celiac disease in patients with severe liver disease: gluten-free diet may reverse hepatic failure

BACKGROUND & AIMS: Mild liver abnormalities are common in patients with celiac disease and usually resolve with a gluten-free diet. We investigated the occurrence of celiac disease in patients with severe liver failure. METHODS: Four patients with untreated celiac disease and severe liver disease are described. Further, the occurrence of celiac disease was studied in 185 adults with previous liver transplantation using serum immunoglobulin A endomysial and tissue transglutaminase antibodies in screening. RESULTS: Of the 4 patients with severe liver disease and celiac disease, 1 had congenital liver fibrosis, 1 had massive hepatic steatosis, and 2 had progressive hepatitis without apparent origin. Three were even remitted for consideration of liver transplantation. Hepatic dysfunction reversed in all cases when a gluten-free diet was adopted. In the transplantation group, 8 patients (4.3%) had celiac disease. Six cases were detected before the operation: 3 had primary biliary cirrhosis, 1 had autoimmune hepatitis, 1 had primary sclerosing cholangitis, and 1 had congenital liver fibrosis. Only 1 patient had maintained a long-term strict gluten-free diet. Screening found 2 cases of celiac disease, 1 with autoimmune hepatitis and 1 with secondary sclerosing cholangitis. CONCLUSIONS: The possible presence of celiac disease should be investigated in patients with severe liver disease. Dietary treatment may prevent progression to hepatic failure, even in cases in which liver transplantation is considered.     

Bipolar radiofrequency thermal ablation of the soft palate in habitual snorers without significant desaturations assessed by magnetic resonance imaging

Sleep-disordered breathing, including habitual snoring, is a major health problem. Treatment of primary habitual snoring should be individualized using both conservative and active treatment methods. Active surgical interventions are, however, associated with significant morbidity. Therefore, procedures causing far less morbidity should be preferred. Our aim was to assess the efficacy and acceptability of bipolar radiofrequency thermal ablation of the soft palate in habitual snorers without significant desaturations associated with excessive daytime sleepiness. We treated 20 nonobese habitual snorers (median age, 43 years, range 35-63). All the patients had the major site of obstruction at the level of the soft palate, and they were treated on an outpatient basis in two treatment sessions separated by 1 week. The pretreatment and post-treatment symptoms and findings as well as the overall efficacy of the procedure were evaluated by questionnaires, visual analogue scales, and magnetic resonance imaging. All the questionnaires showed a statistically significant change, indicating decreased snoring and daytime sleepiness. The magnetic resonance studies showed that the procedure induced notable T1-signal alterations in the treated tissue, and when compared with the pretreatment images, certain dimensions of the soft palate were significantly changed. Bipolar radiofrequency thermal ablation of the soft palate seems to be well tolerated and effective regarding primary habitual snorers without significant desaturations associated with excessive daytime sleepiness.