Correction of Severely Contracted Nose.

BACKGROUND: Severely contracted nose is manifested with a tight and hardened nasal envelope. Expansion of the contracted skin is an important first step in correcting these revision cases. The underlying weak lower lateral cartilage makes the tip projection structurally difficult to achieve and maintain without rigid supporting cartilage grafting. METHODS: A total 59 of patients were treated with isolated adipose-derived stromal cells before revision surgery to soften the nasal envelope. Adipose tissues were digested at 37°C with sterile 0.075% collagenase type 2. The average isolated adipose-derived stromal cell count of each serial injection was 5 × 10 cells (total injection volume, 0.5 ml; 1 × 10 cells/ml). Intraoperatively, the lower lateral cartilage was released from surrounding scar tissue to allow for advancement. Rib cartilage and other autologous grafts were used in reconstruction of the internal framework. RESULTS: The follow-up period ranged from January of 2009 to April of 2014. The mean follow-up period was 10 months. Fifty-one of 59 patients were satisfied with their results. Eight patients underwent revision surgery for the following: infection (two patients), deviation (one patient), warping (two patients), and cosmetic dissatisfaction (three patients). There were two cases of additional warping, but the patients refused revision surgery. Nine patients required additional adipose-derived stromal cell injections at the tip. CONCLUSIONS: The combination of isolated fat grafting to soften the nasal skin envelope and rigid tip support results in correction of silicone-induced contracted nose. There were no incidences of recurrent nasal contraction or ischemic injury. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Enhanced hypothalamic leptin signaling in mice lacking dopamine D2 receptors.

The dopamine D(2) receptor (D2R) plays a critical role in diverse neurophysiological functions. D2R knock-out mice (D2R(-/-)) show reduced food intake and body weight while displaying an increased basal energy expenditure level, compared with their wild type littermates. Thus, these mice show a lean phenotype. D2R(-/-) mice displayed increased leptin sensitivity, and leptin injection induced increased phosphorylation of the hypothalamic signal transducer and activator of transcription 3 (STAT3) in D2R(-/-) mice relative to wild type littermates. Using double immunofluorescence histochemistry, we have demonstrated that D2Rs are present in leptin-sensitive STAT3-positive cells in the arcuate nucleus of the hypothalamus and that leptin injection induces STAT3 phosphorylation in hypothalamic neurons expressing D2Rs. Stimulation of D2R by the D2R agonist quinpirole suppressed the leptin-induced STAT3 phosphorylation and nuclear trans-localization of phospho-STAT3 in the hypothalamus of wild type mice. However, this regulation was not detected in the D2R(-/-) mice. Treatment of D2R agonist and antagonist could modulate the leptin-induced food intake and body weight changes in wild type mice but not in D2R(-/-) mice. Together, our findings suggest that the interaction between the dopaminergic system and leptin signaling in hypothalamus is important in control of energy homeostasis.

The dopamine D2 receptor regulates the development of dopaminergic neurons via extracellular signal-regulated kinase and Nurr1 activation.

Because the dopaminergic pathways in the midbrain have been closely associated with serious neuropsychiatric disorders, the elucidation of the mechanisms underlying dopaminergic neuronal development should provide some important clues for related disorders. In mice lacking the dopamine D2 receptor (D2R-/-), stereological cell counting analysis showed that the number of mesencephalic tyrosine hydroxylase (TH) cells was significantly low during ontogeny, compared with that observed in wild-type (WT) mice, thereby indicating an alteration in dopaminergic neuronal development in the absence of D2R. The results of immunohistochemical and reverse transcription-PCR analyses revealed that the expression of Nurr1, an orphan nuclear receptor, as well as Ptx3 expression, was selectively reduced in D2R-/- mice during the embryonic stage. A reporter gene assay using the Nur response element linked to the luciferase reporter gene indicated that the stimulation of D2R results in the activation of the Nurr1-mediated reporter gene. This D2R-mediated Nur response element-dependent transcriptional activity was regulated via the activation of extracellular signal-regulated kinase (ERK). Furthermore, quinpirole treatment was shown to elicit an increase in the number of TH-positive neurons, as well as the neuritic extension of TH neurons, coupled with ERK activation and Nurr1 activation in the TH-positive neurons in primary mesencephalic cultures from WT mice. However, this regulation was not detected in the D2R-/- mice. These results suggest that signaling through D2R in association with Nurr1 using ERK, plays a critical role in mesencephalic dopaminergic neuronal development.