Increased and persistent circulating insulin-like growth factor II in neonatal transgenic mice suppresses developmental apoptosis in the pancreatic islets

In rats, a proportion of pancreatic beta-cells are deleted by apoptosis in the second week of postnatal life and replaced by endocrine cell neogenesis from pancreatic ductal epithelium. This coincides with a reduction in pancreatic insulin-like growth factor II (IGF-II) expression, and IGF-II has been shown to act as a beta-cell survival factor in vitro. To examine whether IGF-II regulates beta-cell apoptosis in vivo, an IGF-II transgenic mouse model was used in which mouse IGF-II is overexpressed in skin, gut, and uterus driven by a keratin promoter, so that circulating IGF-II is retained postnatally. Mice were killed between postnatal days 7 and 26, and the pancreas was examined histologically. Apoptotic cells were visualized by the terminal deoxynucleotidyltransferase-mediated deoxy-UTP nick end labeling method, and proliferating cells were examined by immunohistochemistry for proliferating cell nuclear antigen. In nontransgenic mice, serum IGF-II was absent by 26 days, but mean (+/-SEM) values were 45+/-9 ng/ml (n = 5) in transgenic animals. A 2- to 3-fold rise in islet cell apoptosis was seen in normal animals between days 11 and 16, but this was substantially decreased in IGF-II transgenic mice (day 11; control, 12+/-1%; transgenic, 6+/-1%; P < 0.01; n = 5). Consequently, islets from IGF-II transgenic mice had a significantly greater mean area from days 11-16, but the proportions of beta- and alpha-cells and circulating insulin levels were not changed. Islet cell DNA synthesis was increased in transgenic mice on days 13 and 16. The total islet number per section did not alter. The results show that a persistent presence of circulating IGF-II postnatally alters endocrine pancreatic ontogeny in the mouse and largely prevents the wave of developmental apoptosis that precipitates beta-cell turnover in neonatal life.     

ISYQOL: a Rasch-consistent questionnaire for measuring health-related quality of life in adolescents with spinal deformities

Background Context

Spinal deformities are commonly associated with poor health-related quality of life (HRQOL). Several questionnaires (eg, Scoliosis Research Society-24 [SRS-24] and Scoliosis Research Society-22 [SRS-22]) have been developed to evaluate HRQOL in these conditions. In adults as well as during growth, the HRQOL is considered one of the most relevant outcomes of both conservative and surgical treatments. Rasch analysis is a powerful statistical technique for developing high-quality and valid questionnaires. The SRS-24 and SRS-22 have been evaluated using the Rasch analysis but showed poor measurement properties. Thus, a proper measure of HRQOL in people with a spine condition is still missing.

Multidisciplinary approach of a crown-root fracture using intentional replantation: a case report

Crown-root fractures are complex traumatic injuries that require multidisciplinary management and afford uncertain prognosis. The purpose of this clinical article was to report the case of crown-root fracture where a multidisciplinary approach was successfully executed. A 10-year-old male patient who suffered a complicated crown-root fracture on a permanent maxillary central incisor was treated using an intentional 180°-rotation replantation technique, followed by endodontic therapy and restoration with resin composite. Two years after the initial treatment, the case was stable and the tooth was restored with a resin core and a ceramic crown. This article describes how adequate multidisciplinary treatment planning, coordination, and execution are necessary for similar cases to be properly managed. It can be concluded that the intentional replantation with 180°-rotation allowed a more conservative approach, showing, in this case, a clinical success without resorption.     

Validation of the cantharidin-induced skin blister as an in vivo model of inflammation

AIM

Pharmacological profiling techniques, such as the cantharidin-induced skin blister, may be used to assess the anti-inflammatory properties of novel drugs. However, no data are available on the reproducibility of this technique or on the blocking effect of anti-inflammatory drugs, such as anti-TNF and corticosteroids.

METHODS

A group of 30 healthy subjects were randomized into three parallel groups treated with placebo, oral methylprednisolone 20 mg day⁻¹ for 7 days or anti-tumour necrosis factor (TNF) (adalimumab, Humira®, Abbott) 40 mg s.c. single dose. A first blister was induced at baseline and collected, immediately before the start of treatment and a second blister was obtained 7 days after the start of treatment. The total number of cells, the cell viability and the differential cell count were evaluated by two independent observers, who were blind to treatment. anova was used to compare change from baseline among the three groups before pairwise comparisons.

RESULTS

Among the placebo group, there was no significant difference in the total cell count, neutrophils, eosinophils and monocytes between day 1 and day 7. Methylprednisolone inhibited the eosinophil influx in mean % (95% CI) (−1.0 (−1.7, −0.3); P < 0.02) and absolute (P < 0.02) values, while anti-TNF inhibited the neutrophil influx in mean % (95% CI) (−19.3 (−29.5, −9.1); P < 0.01) and absolute (P < 0.05) values.

CONCLUSIONS

The cantharidin-induced skin blister is a safe, well tolerated and reproducible procedure. Pre-treatment with anti-TNF or methylprednisolone inhibited the neutrophilic or eosinophilic trafficking, respectively. It could be useful in profiling anti-inflammatory drugs regarding their effects on the cellular inflammatory response.     

Time Course of Endotoxin-Induced Airways’ Inflammation in Healthy Subjects

Few data are available on the kinetic of the airways’ inflammation induced by inhaled endotoxin in a given subject. The purpose of this study was to evaluate in healthy subjects the time-related endotoxin-induced airways’ inflammation. The cells counts from the induced-sputum were evaluated before, 6 and 24 h, and 7 days after an exposure to 20 mcg inhaled endotoxin, in eight pre-selected volunteers. To avoid interference of the induced-sputum procedure on the response to endotoxin, each time-point was evaluated in randomized order at 2-weeks interval after three separate inhalations of endotoxin. A significant rise of the relative number of lymphocytes (p < 0.05) and polymorphonuclear neutrophils (PMN; p < 0.02) and of the absolute number of PMN (p < 0.05) occurring at 6 h, followed by an increase of the absolute number of the total viable cells (p < 0.01), macrophages (p < 0.001), neutrophils (p < 0.01), and lymphocytes (p < 0.05) at 24 h after endotoxin inhalation. The inflammatory response recovered totally after 7 days. In human beings, the inhalation of endotoxin induced a transient airway inflammation after 6 h, peaked at 24 h and recovered after 7 days. When repeated endotoxin inhalations are used as a model of inflammation, a wash-out period of at least 7 days should be applied between each exposure in each subject.