Macaca fascicularis

Chronic vascular access is often needed in experimental animal studies, and vascular access ports (VAP) have been proposed as an alternative to conventional venipuncture. We previously reported on VAP implantation by using femoral venous cutdown (FVC) and tunneling. In an attempt to decrease the moderate complications associated with the FVC method, we developed the single-incision, peripheral-insertion (SIPI) method. In a retrospective evaluation, 92 FVC procedures were compared with 113 SIPI procedures in cynomolgus and rhesus macaques and baboons with as much as 2.5 y of follow-up. The rate of complications was significantly lower for the SIPI method than for the FVC method (19.4% versus 33.7%), particularly in regard to infectious complications (8.0% versus 27.3%, respectively). In addition, VAP patency for blood sampling and fluid infusion was significantly better for the SIPI method than for the FVC method, with 1-y patency rate of 83% and 46%, respectively, and 2-y patency ra...

This study was designed to determine the bioavailability and dose linearity and proportionality of ganciclovir after multiple oral administrations of 3,000 mg to 6,000 mg per day. In an open-label, randomized, four-treatment crossover design, 24 patients seropositive for human immunodeficiency virus (HIV) and cytomegalovirus (CMV) received in random order multiple oral doses of ganciclovir 1,000 mg every 3 hours (six times a day), 1,000 mg four times a day, and 1,000 mg three times a day and a single 5-mg/kg intravenous infusion (over 1 hour) of ganciclovir. Blood samples for pharmacokinetic determinations were obtained on day 3 of each oral regimen and on the day of the intravenous infusion over a 24-hour time interval. Mean steady-state average serum concentrations of ganciclovir were 0.54, 0.79, and 0.99 microgram/mL, respectively, with the 3, 4, and 6 g/day oral regimens. The steady-state area under the concentration-time curve (AUC0-24) for the 6,000 mg/day oral regimen approached that of the single-dose intravenous regimen. There was a proportional increase in AUC0-24 between the 3 and 4 g/day dosage regimens, but not between the 4 and 6 g/day regimens. This suggests nonlinear absorption of ganciclovir at higher dosages, although the departure from proportionality was less than 11%.

The imbalance in clotting homeostasis, tending towards hypercoagulation, is recognized as the real barrier to the long-term survival of porcine xenografts in pig-to-primate xenotransplatation. The present study aimed to validate in primate blood the applicability of whole blood rotation thromboelastometry, performed by ROTEM®, which evaluates the characteristics of clot formation by dynamic monitoring.ROTEM® (Pentapharm GmbH, Munich, Germany) was used to investigate native coagulation (NATEM®), the intrinsic (INTEM®) and extrinsic (EXTEM®) pathways, the function of fibrinogen (FIBTEM®), and the presence of fibrinolysis in 40 naïve cynomolgus monkeys. Using classic validation approaches, the normal thromboelastographic profile was defined and the influence of haematocrit (Hct,%), platelet count (x109/L), fibrinogen (mg/dl), and factor VIII (FVIII,%) was evaluated.In all four (NATEM®, INTEM®, EXTEM®, FIBTEM®) assays considered, Clotting Time (CT, sec) and Clot Formation Time (CFT, sec) were shorter in primates than humans. Moreover, α-angle (°), Maximum Clot Firmness (MCF, mm), and MaxVel (mm/min) were also higher in primates than humans. No substantial difference was observed for Hct and platelet count between the two species. On the contrary, FVIII was higher in primates than in humans whereas, interestingly enough, fibrinogen levels were lower in monkeys than in humans.ROTEM® depicts a hypercoagulable profile in primates as compared to humans. Taken together these data suggest that, with regard to coagulation, xenotransplantation in cynos may represent a much more difficult situation than xenotransplantation in humans.

The biomechanics of skin and underlying tissues plays a fundamental role in the human sense of touch. It governs the mechanics of contact between the skin and an object, the transmission of the mechanical signals through the skin, and their transduction into neural signals by the mechanoreceptors. To better understand the mechanics of touch, it is necessary to establish quantitative relationships between the loads imposed on the skin by an object, the state of stresses/strains at mechanoreceptor locations, and the resulting neural response. Towards this goal, 3-D finite-element models of human and monkey fingertips with realistic external geometries were developed. By computing fingertip model deformations under line loads, it was shown that a multi-layered model was necessary to match previously obtained in vivo data on skin surface displacements. An optimal ratio of elastic moduli of the layers was determined through numerical experiments whose results were matched with empirical ...

This study examined the corticospinal tract in monkey by utilizing the anterograde transport of wheat germ lectin conjugated to horseradish peroxidase (WGA HRP) at the light microscopic level and the axonal transport of 3H-proteins with both light and electron microscopic autoradiographic techniques. The animals survived 3–9 days after the injections of 3H-leucine or 3H-leucine/WGA HRP into either motor or sensory cortices. With the laminar schema of Rexed as a guide to the layers of the spinal gray matter, qualitative and quantitative analyses of labeled projections of the corticospinal tract (CST) were made. With the light microscope, axons from the sensory cortex labeled with WGA-HRP could be observed in the contralateral spinal gray from lamina I to the border of laminae VI/VII, the heaviest distribution being located in medial III–VI. There was a small ipsilateral projection to V and VI. With 3H label, laminae I and II revealed few overlying silver grains; many grains overlay laminae III–VI. Projections from the motor cortex labeled with either WGA-HRP or 3H extended from the contralateral laminae III/IV border into the motor nucleus (lamina IX) and were seen to be somewhat more dense in the lateral areas of the spinal gray. The motor cortex projected heavily to ipsilateral VIII, and in sparse amounts to ipsilateral V and VI.Electron microscopy of radioactive axons from the sensory cortex to dorsal horn revealed many radioactive myelinated fibers and some labeled non-myelinated axons. Labeled terminals contacted medium to small dendrites; there were a few labeled C-type profiles in glomeruli and occasional axo-axonal or dendro-axonal contacts, the labeled cortical axons being the postsynaptic structure. In ventral horn following motor cortex injections, the labeled axons were all myelinated. The synaptic contacts were found on small, medium, and large proximal dendrites as well as on cell bodies. Labeled terminals which formed the central element in glomeruli were also seen in this region. Most of the labeled corticospinal terminals in dorsal and ventral horn contained rounded vesicles, but a significant number revealed pleomorphic vesicles. The relationship of these morphological findings to physiological studies of the CST is presented.

There is renewed interest in the development of poxvirus vector-based HIV vaccines due to the protective effect observed with repeated recombinant canarypox priming with gp120 boosting in the recent Thai placebo-controlled trial. This study sought to investigate whether a heterologous prime-boost-boost vaccine regimen in Chinese cynomolgus macaques with a DNA vaccine and recombinant poxviral vectors expressing HIV virus-like particles bearing envelopes derived from the most prevalent clades circulating in sub-Saharan Africa, focused the antibody response to shared neutralising epitopes. Three Chinese cynomolgus macaques were immunised via intramuscular injections using a regimen composed of a prime with two DNA vaccines expressing clade A Env/clade B Gag followed by boosting with recombinant fowlpox virus expressing HIV-1 clade D Gag, Env and cholera toxin B subunit followed by the final boost with recombinant modified vaccinia virus Ankara expressing HIV-1 clade C Env, Gag and huma...