ABI793 treatment effectively prevents graft rejection in Cynomolgus monkeys. Evidence for rare thromboembolic events, as also previously observed with different anti-human CD154 mAbs, suggests that thromboembolic complications may be a class effect of anti-CD154 mAbs, unrelated to their epitope specificity.
The purpose of this study was to obtain sonographic measures of normal kidneys in cynomolgus monkeys (Macaca fascicularis). The kidneys of 27 healthy female cynomolgus monkeys were examined with two-dimensional, duplex and power Doppler under sedation or general anesthesia. Except for shape and sinus echogenicity, the kidneys of the cynomolgus monkey are morphologically similar to those of humans. Left kidney volume estimations (mean, 5.1 cm3) were significantly smaller (P<0.001) than those of the right (mean, 5.9 cm3), and both increased significantly with increasing body weight (P<0.05, r = 0.408). The mean resistive index (RI) of ketamine-sedated monkeys was 0.54, with an upper limit of 0.74 for the renal artery. The mean RI under general anesthesia was 0.65, with an upper limit of 0.77. Morphologic and Doppler ultrasound assessments of the kidneys can be consistently performed in the conscious cynomolgus monkey, and anesthesia can have hemodynamic effects that alter the Doppler arterial waveform.
A nonhuman primate (NHP) study was designed to evaluate in nonlife-supporting kidney allografts the progression from acute rejection with transplant endarteritis (TXA) to chronic rejection (CR) with sclerosing vasculopathy. Group G1 (n = 6) received high cyclosporine A (CsA) immunosuppression and showed neither TXA nor CR during 90 days posttransplantation. Group G2 (n = 6) received suboptimal CsA immunosuppression and showed severe TXA with graft loss within 46 days (median). Arterial intimal changes included infiltration of macrophages and T lymphocytes (CD3, CD4, CD8) with few myofibroblasts, abundant fibronectin/collagen IV, scant collagens I/III, high rate of cellular proliferation and no C4d accumulation along peritubular capillaries. Group G3 (n = 12) received suboptimal CsA and anti-rejection therapy (rabbit ATG + methylprednisolone + CsA) of TXA. Animals developed CR and lost grafts within 65 days (median). As compared to G2, the arterial intimal changes showed less macrophages and T lymphocytes, an increased number of myofibroblasts, abundant fibronectin/collagen IV and scar collagens I/III, C4d deposition along capillaries in 60% of animals and transplant glomerulopathy in 80% of animals.In conclusion, CR is an immune stimulated process initiated during TXA with the accumulation and proliferation of myofibroblasts, and progressive deposition of collagens in the intima. Our experimental design appears well suited to study events leading to CR.
FTY720 is an effective immunosuppressant in prevention of acute kidney allograft rejection in cynomolgus monkeys and synergizes with cyclosporine and/or RAD in yielding rejection-free allograft survival.
1 Pindolol is a non-selective li-adrenoceptor blocking agent; its affinity to adrenoceptors in guinea pig atria (p1) is not significantly different from that in guinea pig trachea (I31 + 02) and canine vascular smooth muscle (132)-2 Pindolol displays a striking diversity of agonist activities in isolated tissues. Stimulant effects correspond to 40-50% of the maximum effects of isoprenaline in isolated kitten atria and guinea pig trachea and to only 10% in guinea pig atria. Effects in canine isolated mesenteric vessels are those of a full agonist, maximum responses equalling those of isoprenaline. These findings suggest that the stimulant effects of pindolol are exerted principally on 032-adrenoceptors.3 Cardiac stimulation produced by pindolol in the dog is sufficient to compensate for the cardiac depression resulting from blockade of ,B-adrenoceptors in the heart. Reductions in cardiac output and compensatory increases in total peripheral resistance do not occur or are much smaller than those produced by 1-adrenoceptor blocking agents lacking sympathomimetic activity.4 Pindolol-induced relaxation of bronchial smooth muscle prevents or minimizes the bronchoconstrictor effects of injected spasmogens in the cat. 5 Pindolol has marked vasodilator activity, small doses reducing femoral and mesenteric vascular resistance by approximately 30%. Doses comparable to those used in hypertensive patients lower blood pressure by 20 mmHg in non-anaesthetized dogs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.