Home About us Contact
|
Home About us Contact | ||
|
|
||
Monkey Model (monkey + model)
Selected AbstractsfMRI of Generalized Absence Status Epilepticus in Conscious Marmoset Monkeys Reveals Corticothalamic ActivationEPILEPSIA, Issue 10 2004Jeffrey R. Tenney Summary:,Purpose: A nonhuman primate model of generalized absence status epilepticus was developed for use in functional magnetic resonance imaging (fMRI) experiments to elucidate the brain mechanisms underlying this disorder. Methods: Adult male marmoset monkeys (Callithrix jacchus) were treated with ,-butyrolactone (GBL) to induce prolonged absence seizures, and the resulting spike,wave discharges (SWDs) were analyzed to determine the similarity to the 3-Hz SWDs that characterize the disorder. In addition, blood-oxygenation-level,dependent (BOLD) fMRI was measured at 4.7 Tesla after absence seizure induction with GBL. Results: Electroencephalographic recordings during imaging showed 3-Hz SWDs typical of human absence seizures. This synchronized EEG pattern started within 15 to 20 min of drug administration and persisted for >60 min. In addition, pretreatment with the antiepileptic drug, ethosuximide (ESM), blocked the behavioral and EEG changes caused by GBL. Changes in BOLD signal intensity in the thalamus and sensorimotor cortex correlated with the onset of 3-Hz SWDs. The change in BOLD signal intensity was bilateral but heterogeneous, affecting some brain areas more than others. No significant negative BOLD changes were seen. Conclusions: The BOLD fMRI data obtained in this marmoset monkey model of absence status epilepticus shows activation within the thalamus and cortex. [source] Cellular localization of epidermal-type and brain-type fatty acid-binding proteins in adult hippocampus and their response to cerebral ischemiaHIPPOCAMPUS, Issue 7 2010Dexuan Ma Abstract This study aimed at an analysis of expression of epidermal-type and brain-type fatty acid-binding proteins (E-FABP and B-FABP, also called FABP5 and FABP7, respectively) in adult hippocampus and their potential value as neuroprotective factors after ischemic brain damage in monkey model. The immunostaining and Western blotting results show that FABP5 was mainly expressed in neurons, whereas FABP7 was primarily expressed in astrocytes and progenitors of the subgranular zone (SGZ). Interestingly, FABP5 expression in neurons increased in cornu Ammonis 1 (CA1) and remains stable within dentate gyrus (DG) after ischemia; FABP7 expression increased within both CA1 and SGZ. This indicates a potential role for FABP5 and FABP7 in intracellular fatty acid transport within different neural cells. The change in FABP5,7 expression within CA1 and DG of the adult postischemic hippocampus was compatible with previous findings of downregulation in CA1 neurons and upregulation in SGZ progenitor cells after ischemia. Altogether, the present data suggest that polyunsaturated fatty acids, such as docosahexaenoic acid, may act via FABP5 or 7 to regulate adult postischemic hippocampal neuronal antiapoptosis or neurogenesis in primates. © 2009 Wiley-Liss, Inc. [source] Inhalation efficacy of RFI-641 in an African green monkey model of RSV infectionJOURNAL OF MEDICAL PRIMATOLOGY, Issue 2 2003W.J. Weiss Abstract: Human respiratory syncytial virus (RSV) is a major cause of acute upper and lower respiratory tract infections. RFI-641 is a novel RSV fusion inhibitor with potent in vitro activity. In vivo efficacy of RFI was determined in an African green monkey model of RSV infection involving prophylactic and therapeutic administration by inhalation exposure. Inhalation was with an RFI-641 nebulizer reservoir concentration of 15 mg/ml for 15 minutes (short exposure) or 2 hours (long exposure). Efficacy and RFI-641 exposure was determined by collection of throat swabs, nasal washes and bronchial alveolar lavage (BAL) on selected days. The short-exposure group (15 minutes) exhibited no effect on the nasal, throat or BAL samples. The throat and nasal samples for the long-exposure group failed to show a consistent reduction in viral titers. RFI-641 2 hours exposure-treated monkeys showed a statistically significantly log reduction for BAL samples of 0.73,1.34 PFU/ml (P -value 0.003) over all the sampling days. Analysis indicates that the long-exposure group titer was lower than the control titer on day 7 and when averaged across days. The results of this study demonstrate the ability of RFI-641 to reduce the viral load of RSV after inhalation exposure in the primate model of respiratory infection. [source] Inhaled vs subcutaneous effects of a dual IL-4/IL-13 antagonist in a monkey model of asthmaALLERGY, Issue 1 2010A. Tomkinson Abstract Background:, Pitrakinra is a recombinant protein derived from human interleukin-4 (IL-4) that binds to IL-4R, and acts as a competitive antagonist of IL-4 and IL-13. The studies reported here compare the dose-ranging effects of pitrakinra on allergen-induced airway hyperresponsiveness (AHR) and airway eosinophilia when administered subcutaneously (s.c.) or by inhalation to the Ascaris suum -sensitive cynomolgus monkey for the purpose of elucidating the primary site of pitrakinra's anti-asthmatic action. Methods:, Airway responsiveness to inhaled methacholine and bronchoalveolar lavage cell composition was determined before and after three allergen exposures with a 1-week course of twice-daily (b.i.d.) s.c. or inhaled pitrakinra or placebo treatment. Results:, Treatment with s.c. pitrakinra significantly reduced allergen-induced AHR, with a maximum effect of a 2.8- to 3.8-fold increase in methacholine PC100 relative to control (P < 0.05) observed at b.i.d. s.c. doses of 0.05,0.5 mg/kg. Inhaled pitrakinra also significantly reduced AHR with a similar maximum effect of a 2.8- to 3.2-fold increase in methacholine PC100 relative to control (P < 0.05) at nominal b.i.d. doses of 3,100 mg. The maximal effect on AHR following inhalation was observed at a plasma concentration which exhibited no efficacy via the subcutaneous route. The effect of pitrakinra on lung eosinophilia was not statistically significant following either route of administration, although lung eosinophil count was reduced in all studies relative to control. Conclusion:, Local administration of pitrakinra to the lung is sufficient to inhibit AHR, one of the cardinal features of asthma, indicating the therapeutic potential of inhaled pitrakinra in the treatment of atopic asthma. [source] Rhesus monkey model for Leishmania major transmitted by Phlebotomus papatasi sandfly bitesMEDICAL AND VETERINARY ENTOMOLOGY, Issue 1 2001R. J. Probst Summary Leishmaniasis research needs a near-human model for investigations of natural infection processes, immunological responses and evaluation of treatments. Therefore, we developed a reproducible system using Leishmania major Yakimoff & Schokhor (Trypanosomatidae: Kinetoplastida), the cause of Old World zoonotic cutaneous leishmaniasis (ZCL), transmitted to rhesus monkeys Macaca mulatta (Zimmerman) (Primates: Cercopithecidae) by sandfly bites of experimentally infected Phlebotomus papatasi (Scopoli) (Diptera: Psychodidae). Eight monkeys of presumed Indian origin (Leishmania naïve) were exposed to bites of female sandflies that had been infected with L. major by membrane-feeding on human blood seeded with amastigotes isolated from hamster footpad lesions. Infection rates of membrane-fed sandflies averaged >,85% seven days after the infective feed, with uniformly high numbers of promastigotes in the stomodaeal valve region of the sandfly gut. Nodules and ulcerating dermal lesions developed on 7/8 monkeys 2,4 weeks post-bite and persisted for 3,7 months. Monkeys also developed satellite lesions beyond the area of sandfly bites on the head, but not on the chest. Three re-challenged monkeys developed lesions that healed faster than lesions from their primary challenges. After infection, monkeys developed delayed type hypersensitivity (DTH) responses to a panel of Leishmania skin test antigens (LSTA) and, when tested by ELISA and IFA, showed significant post-infection antibody titres which typically rose for ,170 days and then gradually receded during the next 100 days following the first challenge. After the second challenge, antibody titres spiked higher within ,50 days and receded more rapidly. In contrast, four rhesus macaques of Chinese origin developed no lesions following infected sandfly bites, although they raised antibodies and LSTA reactions, indicating subclinical infection. [source] Skeletal health: primate model of postmenopausal osteoporosisAMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009S.Y. Smith Abstract Currently, the nonhuman primate is the most widely used large animal model to evaluate the safety and efficacy of new drug entities to treat or prevent estrogen-deficiency-induced bone loss and osteoporosis. Surgical ovariectomy (OVX) induces a state of high bone turnover and rapid bone loss establishing a new steady-state bone mass within 8,9 months. Many systems in the monkey are similar to humans, including skeletal and reproductive physiology and the immune system, making this a plausible model suitable to evaluate the effects of new bone drugs. The long-term sequelae following OVX and withdrawal of monthly exposure to cyclic reproductive hormones in older female monkeys (cynomolgus and rhesus) mimics estrogen depletion and postmenopausal bone loss occurring in women. Characterization of the primate model revealed an apparent limitation to the extent of bone loss. Animals lose bone mass after OVX, but the extent of the bone loss cannot be described as osteoporotic. The small differences between OVX and sham-operated controls in many important bone measurements is overcome by including 15,20 animals per group to provide adequate statistical power. The long-term, at least 16 month, bone safety studies performed to satisfy regulatory guidelines provide an opportunity to study treatment effects for an extended period not covered in shorter-term safety studies. In vivo end-points such as densitometry and biochemical markers translate easily to clinical use, while biomechanical end-points that cannot be measured clinically can be used to predict fracture prevention. To date, the monkey OVX model has been used to support submissions for many new drugs including anabolics, bisphosphonates and selective estrogen receptor modulators. Despite its limitations, the OVX monkey model remains the best characterized of the large animal models of osteopenia and has become integral to osteoporosis drug development. Am. J. Primatol. 71:752,765, 2009. © 2009 Wiley-Liss, Inc. [source] Fetal, infant, adolescent and adult phenotypes of polycystic ovary syndrome in prenatally androgenized female rhesus monkeysAMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009David H. Abbott Abstract Old World monkeys provide naturally occurring and experimentally induced phenotypes closely resembling the highly prevalent polycystic ovary syndrome (PCOS) in women. In particular, experimentally induced fetal androgen excess in female rhesus monkeys produces a comprehensive adult PCOS-like phenotype that includes both reproductive and metabolic dysfunction found in PCOS women. Such a reliable experimental approach enables the use of the prenatally androgenized (PA) female rhesus monkey model to (1) examine fetal, infant and adolescent antecedents of adult pathophysiology, gaining valuable insight into early phenotypic expression of PCOS, and (2) to understand adult pathophysiology from a mechanistic perspective. Elevated circulating luteinizing hormone (LH) levels are the earliest indication of reproductive dysfunction in late gestation nonhuman primate fetuses and infants exposed to androgen excess during early (late first to second trimester) gestation. Such early gestation-exposed PA infants also are hyperandrogenic, with both LH hypersecretion and hyperandrogenism persisting in early gestation-exposed PA adults. Similarly, subtle metabolic abnormalities appearing in young nonhuman primate infants and adolescents precede the abdominal adiposity, hyperliplidemia and increased incidence of type 2 diabetes that characterize early gestation-exposed PA adults. These new insights into the developmental origins of PCOS, and progression of the pathophysiology from infancy to adulthood, provide opportunities for clinical intervention to ameliorate the PCOS phenotype thus providing a preventive health-care approach to PCOS-related abnormalities. For example, PCOS-like traits in PA monkeys, as in PCOS women, can improve with better insulin,glucose homeostasis, suggesting that lifestyle interventions preventing increased adiposity in adolescent daughters of PCOS mothers also may reduce their risk of acquiring many PCOS-related metabolic abnormalities in adulthood. Am. J. Primatol. 71:776,784, 2009. © 2009 Wiley-Liss, Inc. [source] Coronary heart disease of females: lessons learned from nonhuman primatesAMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009Thomas B. Clarkson Abstract The cynomolgus monkey model has contributed to significant advances regarding the understanding of coronary artery atherosclerosis of females. There are currently 8 million women in the United States living with heart disease, necessitating further study and understanding of this leading cause of morbidity and mortality for postmenopausal women. Specifically, studies involving the monkey model have allowed greater understanding of the effect of the stage of reproductive life, time since menopause, and the extent of subclinical atherosclerosis as determinates of estrogen-mediated effects on arteries. Utilizing the commonalities among monkeys and human beings, these studies have shown that postmenopausal atherosclerosis is associated with the premenopausal reproductive timeframe. In addition, monkey studies have shown that estrogen deficiency during the premenopausal stage is extremely relevant regarding the progression of atherosclerosis. After several postmenopausal years, however, studies have shown that estrogen has no beneficial effects on atherosclerosis progression and may, in fact, be deleterious. Studies using the monkey model are currently underway to investigate further uses and possibilities of postmenopausal hormone therapy for treating menopausal symptoms while protecting the breast and uterus and inhibiting the progression of coronary artery atherosclerosis. These studies will hopefully clarify the role of estrogen and eliminate the need for the possibly harmful progestin effects through the use of a highly selective estrogen receptor modulator. Am. J. Primatol. 71:785,793, 2009. © 2009 Wiley-Liss, Inc. [source] Transfer of maternally administered fusogenic liposome-DNA complexes into monkey fetuses in a pregnancy modelTHE JOURNAL OF GENE MEDICINE, Issue 5 2002Makoto Hirano Abstract Background Materno-fetal transfer of intravenously administered liposome-plasmid DNA complexes has been demonstrated only in mice. Studies on its materno-fetal transfer in the pregnant monkey model is needed because of critical differences in placental structure between primates including humans and rodents. Methods The reporter plasmid pEGFP-C1 was formulated in cationic lipid containing polybrene and vesicular stomatitis virus G protein. The fusogenic liposome-plasmid DNA complexes were intradermally injected into pregnant common marmosets (N=2), a New World monkey, near term. DNA extracted from fetal tissues was subjected to PCR for detection of the egfp gene. Confocal microscopy and immunostaining were performed to determine the sites of transgene expression in the fetal organs. Results The egfp gene was detected in fetal blood and major organs (heart, liver, lung). The encoded protein was mainly produced in the endothelial cells of blood vessels in the fetal lungs. Conclusions This is the first report on materno-fetal transfer of intradermally administered fusogenic liposome-plasmid DNA complexes and fetal expression of a transgene in primates. Copyright © 2002 John Wiley & Sons, Ltd. [source] Highly frequent anti-idiotype antibody in cynomolgus monkeys developed against mouse-derived regions of anti-Fas antibody humanized by complementarity determining region graftingBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2009M Saito-Yabe Background and purpose:, We investigated the immunogenicity of a humanized anti-human Fas monoclonal antibody, R-125224, in cynomolgus monkeys to estimate its efficacy, as well as its toxicity in clinical situations. Experimental approach:, R-125224 was intravenously administered to cynomolgus monkeys at single doses of 0.4, 1.2, 6 and 30 mg·kg,1, and the plasma concentrations of R-125224 and anti-R-125224 antibody (ARA) were measured. We conducted a competitive enzyme-linked immunosorbent assay to determine which part of R-125224 was recognized by ARA. We also examined the retention of radioactivity in mononuclear cells and granulocytes after the injection of [125I]-R-125224 to a collagen-induced arthritis monkey model. Key results:, After i.v. administration of R-125224, the elimination of the plasma R-125224 concentrations was accelerated at around 10 days post-dose, and 10 of 12 monkeys were ARA positive. From an epitope analysis of ARA, the ARA produced in monkeys recognized the mouse-derived regions located in complementarity determining regions, but could not recognize the human IgG. After the injection of [125I]-R-125224 to a collagen-induced arthritis monkey model, a significantly longer retention of the radioactivity in mononuclear cells compared to granulocytes was observed. Conclusions and implications:, In monkeys, the development of antibodies against R-125224 is rapid and highly frequent. Our hypothesis is that this highly frequent development of ARA might be due to the binding of R-125224 to immune cells, and its circulation in monkey blood might contribute to an increase in its chances of being recognized as an immunogen. [source] | |||||||||||||