This study assessed whether the intramuscular infusion of a combination cell product represents a viable, effective, and lasting therapeutic modality to improve perfusion in severely ischemic limbs.
Methods: Patients with limb ischemia (n = 26) received an intramuscular (gastrocnemius) infusion of the combination cell product in the most ischemic leg and a placebo product in the (less ischemic) JQ1 cost contralateral leg. Clinical follow-up (months 0.5, 1, 2, and 4 postinfusion) included evaluation of pain-free walking time, ankle-brachial index, perfusion scintigraphy, and quality of life survey.
Results: No adverse events occurred after infusion. Efficacy assessment indicated that after cell infusion there was a
significant improvement in walking time and ankle-brachial index. In addition, technetium-99m-tetrofosmin scintigraphy demonstrated a significant increase of perfusion in the treated limbs compared with the respective control legs.
Conclusions: This phase II clinical trial shows that the use of a combination cell therapy is safe and effective in increasing blood flow in the ischemic legs of patients with limb ischemia.
(J Thorac Cardiovasc Surg 2012;144:377-82)”
“alpha(2)-Adrenergic see more agonists simulate norepinephrine (NE) action on alpha(2) receptors of sympathetic neurons to mediate feedback inhibition of NE release. These agents are used as valuable adjuncts for management of hypertension and for anesthesia. Their action, equivalent to NE on alpha 2 adrenergic receptors, raises the question whether alpha 2 agonists may also target NE transporters (NETs),
another major control mechanism for noradrenergic neurotransmission. We thus investigated the effect of alpha(2) agonists on transport of the NE analog, I-131-metaiodobenzylguanidine (MIBG). Results from this investigation showed that xylazine and dexmedetomidine dose-dependently blocked [H-3]nisoxetine binding in neuron-like SK-N-SH cells. Furthermore, the agents acutely suppressed cellular MIBG uptake in a dose-dependent manner. This effect was uninfluenced by the alpha 2 antagonist yohimbine, but was completely reversed by drug removal. There was no change in membrane NET density by the agents. Moreover, saturation analysis showed that xylazine and dexmedetomidine significantly increased Km without affecting V-max, indicating competitive learn more inhibition of MIBG transport. Thus, the alpha(2) adrenergic agonists xylazine and dexmedetomidine, acutely suppress NET function through competitive inhibition of substrate transport, likely by direct interaction on a region that over-laps with the nisoxetine binding site. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“We developed streamlined, automated purification protocols for the production of milligram quantities of untagged recombinant human cyclophilin-A (hCypA) and untagged human proliferating cell nuclear antigen (hPCNA) from Escherichia coli, using the AKTAxpress(TM) chromatography system.