Comparative lymphatic, ocular, and metabolic phenotypes of Foxc2 haploinsufficient and aP2-FOXC2 transgenic mice.

FOXC2 mutations cause the lymphatic/ocular disorder Lymphedema-Distichiasis (LD), and Foxc2 haploinsufficient mice mimic this disorder. To determine if FOXC2 overexpression might also cause lymphatic and/or ocular abnormalities, we performed dynamic lymphatic imaging (Evans blue dye), ocular tissue examination, and metabolic profiles in mice: transgenic for FOXC2 with an adipocyte (aP2) promoter (aP2-FOXC2 Tg), heterozygous for targeted disruption of Foxc2 (Foxc2+/-), or compound heterozygous and transgenic (Foxc2+/-, Tg) compared to wild-type controls (WT). Foxc2+/-; aP2-FOXC2 Tg; and Foxc2+/-, Tg, exhibited LD's distinctive hyperplastic lymphatic phenotype characterized by increased number of lymphatic channels and lymph nodes as well as retrograde lymph reflux.

Massage therapy in the treatment of lymphedema. Rationale, results, and applications.

The ongoing NCCAM-supported experimental and clinical translational approaches should shed light not only on the physiologic mechanisms underlying the benefits of massage therapy but could also, if successful in defined populations of patients, have a substantial impact by providing a simpler, more cost-effective LE treatment alternative worldwide.

FOXC2 haploinsufficient mice are a model for human autosomal dominant lymphedema-distichiasis syndrome.

Lymphedema-distichiasis (LD) (OMIM 153400) is a rare autosomal-dominant condition characterized by pubertal onset of lower limb lymphedema and an aberrant second row of eyelashes arising from the meibomian glands. In some patients cardiac, skeletal and other defects coexist. We previously identified inactivating, nonsense and frameshift mutations in the forkhead transcription factor FOXC2 in affected members of LD families.

Human immunodeficiency virus type 1 enters brain microvascular endothelia by macropinocytosis dependent on lipid rafts and the mitogen-activated protein kinase signaling pathway.

Brain microvascular endothelial cells (BMVECs) present an incomplete barrier to human immunodeficiency virus type 1 (HIV-1) neuroinvasion. In order to clarify the mechanisms of HIV-1 invasion, we have examined HIV-1 uptake and transcellular penetration in an in vitro BMVEC model. No evidence of productive infection was observed by luciferase, PCR, and reverse transcriptase assays.

Limb volume reduction after physical treatment by compression and/or massage in a rodent model of peripheral lymphedema.

Lack of a standardized experimental counterpart of peripheral lymphedema (LE) in a small animal has hampered research into treatment of this debilitating condition. We recently refined a rodent model consisting of radical unilateral lymphatic/nodal groin excision in conjunction with a circumferential integumental gap, followed by regional irradiation of the groin to reproduce stable unilateral hindlimb LE (1). In the current study, Wistar-Fuzzy rats with established right hindlimb LE, were subdivided into five groups and subjected to one of the following daily physical regimens over a 5-day period: pneumatic compression pumping at 30 torr (PCP); low-stretch multi-layered compressive bandaging using Coban (CB); manual lymphedema drainage (MLD) or a light massage consisting of stationary circular motions using the fingertips; combined physiotherapy (CPT consisting of MLD + CB); and a no treatment or control group (CTRL).