Free PEG Suppresses Anaphylaxis to PEGylated Nanomedicine in Swine.

Covalent conjugation of poly(ethylene glycol) (PEG) is frequently employed to enhance the pharmacokinetics and biodistribution of various protein and nanoparticle therapeutics. Unfortunately, some PEGylated drugs can induce elevated levels of antibodies that can bind PEG, i.e.

Biodistribution of Biomimetic Drug Carriers, Mononuclear Cells, and Extracellular Vesicles, in Nonhuman Primates.

Discovery of novel drug delivery systems to the brain remains a key task for successful treatment of neurodegenerative disorders. Herein, the biodistribution of immunocyte-based carriers, peripheral blood mononuclear cells (PBMCs), and monocyte-derived EVs are investigated in adult rhesus macaques using longitudinal PET/MRI imaging. Cu-labeled drug carriers are introduced via different routes of administration: intraperitoneal (IP), intravenous (IV), or intrathecal (IT) injection.

Improved Tolerability of a Salmonella enterica Serovar Typhimurium Live-Attenuated Vaccine Strain Achieved by Balancing Inflammatory Potential with Immunogenicity.

A notable proportion of -associated gastroenteritis in the United States is attributed to serovar Typhimurium. We have previously shown that live-attenuated Typhimurium vaccine candidate CVD 1921 (I77 Δ Δ) was safe and immunogenic in rhesus macaques but was shed for an undesirably long time postimmunization. In mice, occasional mortality postvaccination was also noted (approximately 1 in every 15 mice).

Isolated from Tuberculinpositive Rhesus Macaques () in the Absence of Disease.

Mycobacterial infections are of primary health concern in NHP colonies in biomedical research. NHP are constantly monitored and screened for Mycobacterium spp. We report 6 Chinese-origin rhesus macaques infected with Mycobacterium kansasii that exhibited positive tuberculin skin tests in the absence of disease.

Differential response of the cynomolgus macaque gut microbiota to Shigella infection.

Little is known about the role of gut microbiota in response to live oral vaccines against enteric pathogens. We examined the effect of immunization with an oral live-attenuated Shigella dysenteriae 1 vaccine and challenge with wild-type S. dysenteriae 1 on the fecal microbiota of cynomolgus macaques using 16 S rRNA analysis of fecal samples.

Histopathology of chronic rejection in a nonhuman primate model of vascularized composite allotransplantation.

Background: Chronic rejection of vascularized composite allografts (VCA) is an emerging phenomenon that may decrease long-term allograft survival and impair allograft function. Although intimal hyperplasia has been reported in human hand transplants, chronic changes in VCAs remain poorly described.

Methods: We developed a nonhuman primate model of face transplantation to evaluate the effect of various immunosuppressive regimens on allograft survival that we have previously reported.

Infrared fluorescence imaging of lymphatic regeneration in nonhuman primate facial vascularized composite allografts.

Background: Clinical vascularized composite allografts (VCA), although performed with good success, have been characterized by rejection episodes and postoperative graft edema. We investigated lymphatic donor-recipient reconstitution and lymphatic regeneration in a nonhuman primate facial VCA model.

Methods: Heterotopic partial face (n = 9) VCAs were performed in cynomolgus macaques.

Nonhuman primate model of fibula vascularized composite tissue allotransplantation demonstrates donor-recipient bony union.

Background: Vascularized composite tissue allotransplantation has demonstrated clinical success with standard immunosuppression in hand and upper extremity transplantation. The authors developed a fibular vascularized composite tissue allotransplantation model in nonhuman primates to investigate healing and rejection patterns of bone and associated tissues.

Methods: Five fibular vascularized composite tissue allotransplantations were performed between mismatched cynomolgus macaques (Macaca fascicularis).

Recurrent idiopathic gingival enlargement in an olive baboon (Papio anubis).

We here describe a case of recurrent gingival enlargement in an olive baboon (Papio anubis). This baboon (a male breeder that had not undergone any experimental procedures) also had shown mild gingival enlargement the 2 y prior to the current lesion. Clinical and histopathologic findings confirmed a diagnosis of idiopathic gingival enlargement.

A challenge model for Shigella dysenteriae 1 in cynomolgus monkeys (Macaca fascicularis).

Shigella dysenteriae type 1 can cause devastating pandemics with high case fatality rates; a vaccine for Shigella is unavailable currently. Because of the risks associated with performing challenge studies with wild-type S. dysenteriae 1 in human clinical trials to advance vaccine development, an improved nonhuman primate model is needed urgently.

Prolonged survival of composite facial allografts in non-human primates associated with posttransplant lymphoproliferative disorder.

Background: Composite tissue allotransplantation may have different immunosuppressive requirements and manifest different complications compared with solid organ transplantation. We developed a non-human primate facial composite tissue allotransplantation model to investigate strategies to achieve prolonged graft survival and immunologic responses unique to these allografts.

Methods: Composite facial subunits consisting of skin, muscle, and bone were heterotopically transplanted to mixed lymphocyte reaction-mismatched Cynomolgus macaques.

Facial subunit composite tissue allografts in nonhuman primates: I. Technical and immunosuppressive requirements for prolonged graft survival.

Background: Widespread application of composite tissue allotransplantation has been impeded by risks of rejection and conventional immunosuppression. The authors have developed a nonhuman primate composite tissue allotransplantation model that demonstrated reliable and long-term success necessary to progress to preclinical studies.

Methods: Composite facial subunits (e.

Methicillin-resistant Staphylococcus non-aureus infection in an irradiated rhesus macaque (Macaca mulatta).

We describe a case of methicillin-resistant Staphylococcus non-aureus infection in a rhesus macaque (Macaca mulatta). The nonhuman primate described was part of a research project that involved whole-body gamma irradiation and subsequently developed acute generalized dermatitis with skin dryness, peeling, and erythema around the eyes. After initial evaluation, which included microbiologic culture and 6 d of medical treatment, the animal was euthanized due to concern regarding a possible outbreak of infectious or zoonotic disease.

Diagnosis and prevention of dissemination of tuberculosis in a recently imported rhesus macaque (Macaca mulatta).

Thirty-four (34) days after arrival at our facility, a recently imported rhesus macaque demonstrated a grade 4/5 reaction to intradermal testing with mammalian old tuberculin and a strong positive response in a serum interferon gamma (IFN-gamma) stimulation assay (Primagam). The affected animal was euthanized to prevent further exposure of the other rhesus in the quarantine room. Necropsy revealed enlarged, caseating mediastinal lymph nodes.

A heterotopic primate model for facial composite tissue transplantation.

The purpose of this study was to develop a nonhuman primate model for heterotopic composite tissue facial transplantation in which to study the natural history of facial transplantation and evaluate immunosuppressive regimens.A composite oromandibular facial segment transplant based on the common carotid artery was evaluated. Flaps from 7 cynomolgus monkeys were transplanted to the groins of 7 recipients at the superficial femoral artery and vein.

Chronic ingestion of (3R,3'R,6'R)-lutein and (3R,3'R)-zeaxanthin in the female rhesus macaque.

Purpose: To investigate how supplementation of the monkey's diet with high doses of lutein (L), zeaxanthin (Z), or a combination of the two affects the plasma levels and ocular tissue deposition of these carotenoids and their metabolites over time and to determine whether these high doses can cause ocular toxicity.

Methods: Eighteen female rhesus monkeys were divided into groups of control (n = 3 control), L-treated (n = 5, 9.34 mg lutein/kg and 0.

Disseminated simian varicella virus infection in an irradiated rhesus macaque (Macaca mulatta).

We describe correlative clinicopathological/virological findings from a simian varicella virus (SVV)-seronegative monkey that developed disseminated varicella 105 days after gamma-irradiation. Twelve other monkeys in the colony were also irradiated, none of which developed varicella. Before irradiation, sera from the monkey that developed disseminated infection and one asymptomatic monkey were available.