Peripheral Heating with Negative Pressure Increases Arterial Blood Flow

Over half (53%) of adults in the United States have some form of diabetes. Traditional treatments have been inadequate in stopping this epidemic suggesting the need for novel therapies. Peripheral heating with negative pressure has previously been shown to reduce blood glucose. The mechanisms behind this effect are unknown but may be related to changes in blood flow to the treated extremity. PURPOSE: To examine changes in flow rate (time averaged mean velocity (TAMV)), vessel cross-sectional area (CSA), and blood flow in the popliteal artery before and during peripheral heating with negative pressure applied to the feet. METHODS: Measures of TAMV, CSA, and blood flow were obtained from the left and right popliteal artery of participants using an ultrasound doppler (Philips CX50, General Electric, USA) before and during peripheral heating with negative pressure. Heat (42°C) was applied to the sole of the feet and negative pressure (-75 mmHg) applied from the feet to the top of the calves while participants remained seated. Vessels were matched for pre and post measures using anatomical landmarks and vessel diameter. Blood flow was calculated as TAMV * CSA. Data are presented as mean (SD) and were analyzed with paired two-sided t-tests. RESULTS: Participants’ (N=8, 4 men and 4 women) demographics are as follows: age: 26.5 (6.1) years; height: 177.7 (9.0) cm; BMI: 25.5 (3.9) kg/m2; body fat: 18.9 (5.7) %. From baseline to during the intervention, TAMV increased 22.3% from 13.0 (13.4) to 16.0 (16.5) cm/sec, p=.059 and 24.7% from 10.5 (10.7) to 13.0 (13.3) cm/sec, p=.067; CSA increased 9.7% from 0.42 (0.34) to 0.46 (0.39) cm2, p=.247, and 10.4% from 0.65 (0.62) to 0.72 (0.70) cm2, p=.122; and blood flow increased 32.3% from 5.2 (3.1) to 7.0 (4.0) mL/sec, p=.115 and 29.5% from 7.2 (7.3) to 9.3 (7.4) mL/sec, p=.032, in the left and right popliteal arteries respectively. CONCLUSION: In this pilot study, applying heat and negative pressure to the feet increased arterial blood flow largely by increasing flow rate with lesser changes to vessel CSA. Without reader blinding and assurance that the same vessel and portion of said vessel were used for pre and post measures, these results should be considered exploratory and interpreted with caution

Src-like Adaptor Protein (Slap) Is a Negative Regulator of T Cell Receptor Signaling

Initiation of T cell antigen receptor (TCR) signaling is dependent on Lck, a Src family kinase. The Src-like adaptor protein (SLAP) contains Src homology (SH)3 and SH2 domains, which are highly homologous to those of Lck and other Src family members. Because of the structural similarity between Lck and SLAP, we studied its potential role in TCR signaling. Here, we show that SLAP is expressed in T cells, and that when expressed in Jurkat T cells it can specifically inhibit TCR signaling leading to nuclear factor of activated T cells (NFAT)-, activator protein 1 (AP-1)–, and interleukin 2–dependent transcription. The SH3 and SH2 domains of SLAP are required for maximal attenuation of TCR signaling. This inhibitory activity can be bypassed by the combination of phorbol myristate acetate (PMA) and ionomycin, suggesting that SLAP acts proximally in the TCR signaling pathway. SLAP colocalizes with endosomes in Jurkat and in HeLa cells, and is insoluble in mild detergents. In stimulated Jurkat cells, SLAP associates with a molecular signaling complex containing CD3ζ, ZAP-70, SH2 domain–containing leukocyte protein of 76 kD (SLP-76), Vav, and possibly linker for activation of T cells (LAT). These results suggest that SLAP is a negative regulator of TCR signaling