Expansion of CD4+CD25+ regulatory T cells by intravenous immunoglobulin: a critical factor in controlling experimental autoimmune encephalomyelitis

The clinical use of intravenous immunoglobulin (IVIg) based on its immunomodulatory and anti-inflammatory potential remains an ongoing challenge. Fcgamma receptor-mediated effects of IVIg, although well elucidated in certain pathologies, cannot entirely account for its proven benefit in several autoimmune disorders mediated by autoreactive T cells. In this study, we show that prophylactic infusion of IVIg prevents the development of experimental autoimmune encephalomyelitis (EAE), an accepted animal model for multiple sclerosis (MS). The protection was associated with peripheral increase in CD4+CD25+Foxp3+ regulatory T cell (Treg) numbers and function. The protection was Treg-mediated because IVIg failed to protect against EAE in mice that were depleted of the Treg population. Rather than inducing de novo generation from conventional T cells, IVIg had a direct effect on proliferation of natural Treg. In conclusion, our results highlight a novel mechanism of action of IVIg and provide a rationale to test the use of IVIg as an immunomodulatory tool to enhance Treg in early onset MS and other autoimmune and inflammatory conditions.     

The epigastric fat transfer: an alternative free flap model in the rat.

A free epigastric fat flap, a modification of the well-known cutaneous groin flap, is described in the rat. Vascular perfusion was successfully restored when transferred to the neck of the rat in 75% of the rats that underwent surgery, as assessed by multiple postoperative stripping tests and select microangiography. This flap offers the advantages of familiar anatomy, ease of postoperative care without risk of flap trauma, and a challenge to microsurgical technique development for successful flap transfer execution. Therefore, this free flap provides an additional animal model for use in microsurgical training as well as a research tool in fat transplantation physiology.     

Lower facial recontouring in craniofacial asymmetry.

The secondary correction of facial asymmetry due to early posterior cranial deformation is presented. The combination of mandibular skeletal reduction of the gonial angle and inferior border, masseter muscle thinning, and auricular setback can be an effective camouflage technique when the facial skeleton and occlusion do not require repositioning.     

Role of natural antibodies in immune homeostasis: IVIg perspective

Intravenous immunoglobulin (IVIg) has increasingly been used for the treatment of autoimmune and systemic inflammatory diseases in addition to supportive therapy of immunodeficient patients. Although a considerable progress has been made in understanding the mechanisms by which IVIg exerts immunomodulatory functions in these diseases, they remain not fully elucidated. The mode of action of IVIg is complex, involving interference with activation of complement and the cytokine network, modulation of: idiotype network, expression of Fc receptors, and activation, differentiation and effector functions of T and B cells and of antigen-presenting cells such as dendritic cells. The therapeutic effects of IVIg most likely reflect the functions of natural antibodies in maintaining immune homeostasis in healthy individuals.     

Comparative study of the anti-inflammatory effect of two intravenous immunoglobulin preparations manufactured by different processes

Intravenous immunoglobulin (IVIG) is increasingly used in the treatment of diverse immune-mediated disorders. Since several preparations of IVIG are available for therapy, it is possible that different manufacturing processes might influence clinical efficacy of IVIG. An insight into the mechanisms of action of such different IVIG preparations is therefore necessary that will provide further guidelines for the utility of IVIG preparations in autoimmune and inflammatory diseases. Since endothelial cells (EC) influence the inflammatory process via production of cytokines, chemokines and expression of adhesive molecules, we analyzed the anti-inflammatory effect on EC of two IVIG preparations: caprylated IVIG (IVIG-C) versus solvent/detergent-treated IVIG (IVIG-SD) preparation. We found that both IVIG preparations inhibit in an equivalent manner, the expression of different pro-inflammatory factors such as IL-6, IL-8, GM-CSF, IL-1beta and TNF-alpha and the adhesion molecules ICAM-1 and VCAM-1. Our results thus suggest that the caprylate while inactivating the virus and enhancing the yield of IgG during IVIG formulation, does not modulate the immunomodulatory properties of IVIG at EC level and that the two preparations show similar anti-inflammatory effects.     

Examination of aerodynamic measures and strain by vibratory source.

OBJECTIVES: Patients with laryngotracheal stenosis often require airway reconstruction. Following surgical intervention, voicing may be produced with either a glottic or supraglottic vibratory source. The objective of this study was to compare average airflow, estimated subglottal pressure, and expert perceptual rating of strain between children with glottic and supraglottic vibratory sources post-airway reconstruction. STUDY DESIGN: This study was a non-randomized prospective study conducted at the Cincinnati Children's Hospital Medical Center (CCHMC), Center for Pediatric Voice Disorders, and included 12 participants with a diagnosis of subglottic stenosis, post-laryngotracheal reconstruction. RESULTS: Expert perceptual ratings of strain were significantly higher for participants with supraglottic versus glottic voicing (P = 0.0001). Although the mean airflow measure was higher for participants with glottic phonation and mean pressure measure was higher for those with supraglottic voicing, these comparisons failed to reach significance. CONCLUSIONS: Patients who exhibit supraglottic phonation patterns demonstrate greater strain during speech, as well as potential alterations to aerodynamic patterns. SIGNIFICANCE: The significant differences in perceived strain by vibratory source are noteworthy, as perceptual quality is always a patient's motivation to seek treatment.