Methods: Patients with lower extremity ischemic tissue loss (Rutherford 5 and 6) received three sets of eight intramuscular injections every 2 weeks of HGF plasmid under duplex ultrasound guidance. Injection locations were individualized for each patient based on arteriographically defined vascular anatomy. Primary safety end point was incidence of adverse events (AE) or serious adverse events (SAE). Clinical
end points included change from baseline in toe brachial index (TBI), rest pain assessment by a 10 cm visual analogue scale (VAS) as well as wound healing, amputation, and survival at 3 and 6 months.
Results: Randomization ratio was 3:1 HGF (n = 21) vs placebo (n = 6). Mean age was 76 +/- 2 years, with 56% male and 59% diabetic. There was no difference in demographics between groups. There was no difference in AEs or SAEs, which consisted mostly of transient HKI-272 supplier injection site discomfort, worsening of CLI, and intercurrent illnesses. Change in TBI significantly improved from baseline at 6 months in the HGF-treated group compared with placebo (0.05 +/- 0.05 vs -0.17 +/- 0.04; P = .047). Change in VAS from baseline
at 6 months was also significantly improved in the HGF-treated group compared with placebo (-1.9 +/- 1.3 vs +0.06 +/- 0.2; P = .04). Complete ulcer healing at 12 months occurred in 31% of the HGF group and 0% of the placebo (P = .28) There was no difference in major amputation of the treated limb (HGF 29% vs placebo 33%) or mortality at 12 months (HGF 19% vs placebo 17%) between groups.
Conclusion: HGF gene therapy using a patient vascular anatomy Carteolol HCl specific delivery technique appears safe, Selleckchem CB-839 maintained limb perfusion, and decreased rest pain in patients with CLI compared with placebo. A larger study to assess
the efficacy of this therapy on more clinically relevant end points is warranted. (J Vase Surg 2010;52:1525-30.)”
“Volatile organic solvents such as toluene are voluntarily inhaled for their intoxicating effects. Solvent use is especially prevalent among adolescents, and is associated with deficits in a wide range of cognitive tasks including attention, behavioral control, and risk assessment. Despite these findings, little is known about the effects of toluene on brain areas mediating these behaviors. In this study, whole-cell patch-clamp recordings were used to determine the effect toluene on neurons within the medial PFC, a region critically involved in cognitive function. Toluene had no effect on measures of intrinsic excitability, but enhanced stimulus-evoked g-amino butyric acid A-mediated inhibitory postsynaptic currents (IPSCs). In the presence of tetrodotoxin (TTX) to block action potentials, toluene increased the frequency and amplitude of miniature IPSCs. In contrast, toluene induced a delayed but persistent decrease in evoked or spontaneous AMPA-mediated excitatory postsynaptic currents (EPSCs).