Cell origin in experimental repair of cricoid cartilage defects treated with recombinant human bone morphogenetic protein-2

We determined the origin of new cartilage and new bone induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) at the site of cricoid cartilage defects in rabbits randomly divided into eight groups. The cricoid cartilage was split vertically along the anterior midline and a strip was excised from the anterior part of the cricoid cartilage in all rabbits. The perichondrium from the anterior part of the cricoid cartilage was trimmed off in four groups; two groups treated with rhBMP-2 and two control groups. In four other groups, the anterior perichondrium was detached and used as a flap with two groups treated with rhBMP-2 and two groups serving as controls. The rabbits were killed 1 week or 4 weeks after surgery. The larynges were removed, fixed and sectioned, and the sections were stained for light microscopy using various cytochemical and immunological techniques. New cartilage was only present close to the host perichondrium adherent to cricoid cartilage in rabbits treated with rhBMP-2. New bone was present 4 weeks after surgery, although calcified matrix and alkaline phosphatase activity could be detected at the site of cricoid defects as early as 1 week after surgery. The cell proliferation marker Ki-67 was strongly expressed in granulation tissue and bone marrow, and it was moderately expressed in muscles adjacent to the cricoid cartilage in rhBMP-2-treated specimens. BMP receptors were strongly expressed in cartilage and moderately expressed in adjacent muscles. We conclude that new cartilage originates from the mesenchymal progenitor cells of host perichondrium adherent to cricoid cartilage in rabbits treated with rhBMP-2. New bone may originate from local muscle.     

Vilse, a conserved Rac/Cdc42 GAP mediating Robo repulsion in tracheal cells and axons

Slit proteins steer the migration of many cell types through their binding to Robo receptors, but how Robo controls cell motility is not clear. We describe the functional analysis of vilse, a Drosophila gene required for Robo repulsion in epithelial cells and axons. Vilse defines a conserved family of RhoGAPs (Rho GTPase-activating proteins), with representatives in flies and vertebrates. The phenotypes of vilse mutants resemble the tracheal and axonal phenotypes of Slit and Robo mutants at the CNS midline. Dosage-sensitive genetic interactions between vilse, slit, and robo mutants suggest that vilse is a component of robo signaling. Moreover, overexpression of Vilse in the trachea of robo mutants ameliorates the phenotypes of robo, indicating that Vilse acts downstream of Robo to mediate midline repulsion. Vilse and its human homolog bind directly to the intracellular domains of the corresponding Robo receptors and promote the hydrolysis of RacGTP and, less efficiently, of Cdc42GTP. These results together with genetic interaction experiments with robo, vilse, and rac mutants suggest a mechanism whereby Robo repulsion is mediated by the localized inactivation of Rac through Vilse.     

Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes

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Associations of Mediterranean diet with psychological ill-being and well-being throughout the pregnancy course: The GESTAFIT project

Quality of Life Research - The relation between diet and maternal mental health during pregnancy might be relevant to prevent adverse materno-foetal outcomes. This study examined the association of...     

Effect of Systemic Pretreatment With Betamethasone on the Bacterial Flora,Inflammatory Response,and Polyp Formation in Experimentally Infected Rabbit Maxillary Sinus Mucosa

To investigate possible effects of corticosteroids on polyp formation and local bacterial colonization, pneumococcal sinusitis was experimentally induced in rabbits pretreated with betamethasone or saline. After 7 days, macroscopic polyps were counted post-mortem and on histologic slides after serial sectioning. Histologic sections were also examined with light microscopy. Macroscopic polyps were significantly fewer in animals given betamethasone, while there was no difference regarding the number of microscopic polyps. Ingrowth of pathogenic microorganisms was found in five of eight rabbits given placebo but in none of the animals treated with corticosteroids (P < 0.05). The reduced number of pathogenic strains in these animals may be explained by a better-preserved local host defense. The lower number of macroscopic polyps in the same animals could be because of a delayed mucosal repair and subsequent polyp formation.     

Combined portal vein embolization and preoperative chemotherapy prior to liver resection for colorectal cancer metastases

Abstract Objective. Compare perioperative course and long-term mortality after liver resection for colorectal cancer (CRC) metastases between patients who had preoperative treatment with portal vein embolization (PVE) and chemotherapy or chemotherapy alone. Methods. Among patients undergoing liver resection for CRC metastases following preoperative chemotherapy treatment, 17 patients who had received preoperative PVE (group A) were compared with 17 matched controls who had no PVE (group B). Perioperative course and long-term mortality were compared between groups A and B and between group A and the entire group of 75 cases with preoperative chemotherapy (group C). Results. Baseline characteristics for the matched groups A and B were similar. Group C included less major resections. Median intraoperative bleeding was 1600 ml in group A, 1200 ml in group B, and 1000 ml in group C (p < 0.05 vs. group A). Median postoperative stay was comparable in all groups (8-9 days). Operation time was 542 min in group A and 464 min in group B (p < 0.01). Mortality after 30 days and 1, 2, and 5 years was similar in all groups. Conclusion. Perioperative outcome and long-term survival did not differ when comparing liver resection for CRC liver metastases preceded by PVE and chemotherapy or chemotherapy alone, except for the operation time. The study supports the safety of this "aggressive" combination approach in patients in need of tumor "downstaging" by chemotherapy and PVE to increase the remnant liver volume.     

Herbal drug BNO 1016 is safe and effective in the treatment of acute viral rhinosinusitis

Conclusion: Daily intake of 480 mg of BNO 1016 for 15 days is an effective treatment in acute viral rhinosinusitis. Objectives: The pooled efficacy data of two similar randomized placebo-controlled clinical trials were analyzed. Safety was evaluated on the basis of the individual trials. Methods: The efficacy analysis was based on 589 patients. Treatment was performed orally with either 3 × 160 mg BNO 1016 (n = 294) or 3 × placebo (n = 295) for 15 days. In both trials patients underwent five visits to the investigational sites. Symptoms were evaluated according to the EPOS 2012 guideline. Ultrasonography was used to confirm the diagnosis at onset of treatment and the remission of symptoms at the last visit. Efficacy was evaluated by the investigator as the mean major symptom score (MSS) at the end of treatment (visit 5, day 14). Patients reported symptoms and social/emotional consequences of rhinosinusitis using a quality of life questionnaire (SNOT-20 GAV). Results: MSS improved during the treatment period by a mean of 10.02 ± 1.61 score points to 2.47 ± 2.55 for BNO 1016 and of 9.87 ± 1.52 to 3.63 ± 3.63 for placebo. Differences between treatment groups at end of therapy (1.16 ± 3.14 score points; p < 0.0001) and patient-assessed quality of life (p = 0.0015) were statistically significant in favor of BNO 1016.