Comparative optic nerve physiology: implications for glaucoma, neuroprotection, and neuroregeneration

The axoplasm of optic nerve axons moves bidirectionally at various speeds along an intra-axonal pressure gradient from the retinal ganglion cell (RGC) somata toward its synapse, and from the synapse towards the RGC somata. The axoplasmic flow of optic nerve axons is precarious even at normal intraocular pressures (IOP) as it moves from the intraocular optic nerve through the scleral lamina cribrosa to the intraorbital optic nerve. The scleral lamina cribrosa is not simply a porous region of the sclera but a specialized extracellular matrix of the central nervous system whose movement during fluctuations in IOP can affect optic nerve axoplasmic flow. The abundant optic nerve blood supply maintains adequate optic nerve head perfusion through a process of vascular autoregulation. Glaucoma is associated with reduced optic nerve axoplasmic flow and compromised optic nerve circulation such that RGC death due to glutamate excitotoxicity and neurotrophin deprivation result.     

Adult‐onset,chronic, cyclic thrombocytopenia in a Rhesus macaque (Macaca mulatta) after dengue virus vaccination and viral challenge

An 8‐year‐old, male Rhesus macaque (Macaca mulatta), previously used for dengue virus (DENV) vaccine research with viral challenge, was presented with adult‐onset, chronic, cyclic thrombocytopenia. Platelet number, morphology, and function were evaluated by automated hematology, peripheral blood smears, electron microscopy, flow cytometry, and impedance aggregometry. Bone marrow was evaluated by cytology. Both serum anti‐dengue nonstructural protein 1 (NS1) antibodies and anti‐platelet antibodies were detected by ELISA. Platelet characterization showed a lack of aggregation to all agonists (ADP, ASP, and collagen), increased activation with increased expression of surface marker (HLA‐ABC), and an absence of surface receptor GPIX during clinical episodes of petechiae and ecchymoses, even in the presence of normal platelet counts. Bone marrow aspirates identified potential mild megakaryocytic hypoplasia. All platelet functions and morphologic attributes were within normal limits during clinically normal phases. Presence of anti‐dengue NS1 serum antibodies confirmed a positive DENV titer 8 years postvaccination. Based on the history and clinical findings, a primary differential diagnosis for this chronic, cyclic platelet pathology was autoimmune platelet destruction with potential bone marrow involvement.     

Living With Urban Baboons: Exploring Attitudes and Their Implications for Local Baboon Conservation and Management in Knysna,South Africa

Humans and primates are coming into increasing contact within urban landscapes. Few studies have investigated how the impacts of living alongside urban primates affect residents’ perceptions of primates. Perceptions have been shown to play a role in conservation interest and management of other urban wildlife species. A survey of suburban residents in Knysna, South Africa was used to explore the relationships between attitudes, level of perceived threat and extent to which baboons were considered a problem, support for local baboon conservation and preferred baboon management strategies. Results indicated that perceived threat was associated with less positive attitudes toward baboons, a greater perceived problem, decreased concern for baboon conservation, and increased advocacy for their lethal removal. This article illustrates the link between respondent perceptions and acceptance of urban primates and the need for further investigation for the wellbeing of both humans and primates.     

灵长类动物食性研究的主要方法及其评价

国内外常见的灵长类动物食性研究方法主要包括实地观察法、粪便分析法、室内笼养饲喂法、胃内容物分析法和毛发中同位素含量测定法等.实地观察法虽然较为可靠,但在林栖胆怯的灵长类动物中难以开展;粪便显微分析法能精确地确定动物所摄入的食物种类,但在显微定量方面必须进行合理的修正才能使实验数据更为精准地反映动物的食性;室内笼养饲喂法可为粪便分析法提供修正参数;胃内容物分析法要以杀死动物作为代价,在目前灵长类动物食性研究中几乎不可行.文章对上述各种方法进行了分析和权衡,总结出应用于灵长类动物食性分析较为可靠的方法,即粪便分析法与室内笼养饲喂法相结合的分析法.     

Laboratory diagnosis of malaria in nonhuman primates

Abstract: Nonhuman primates (NHPs) are commonly used for biomedical research because of the high level of gene homology that underlies physiologic similarity to human beings. Malaria parasites of the genus Plasmodium cause one of the most frequent parasitic diseases of NHPs originating from tropical and subtropical areas and as such represent a significant research confounder. Malaria in NHPs presents a diagnostic challenge especially to those laboratories that see no more than a few malaria cases per year in NHPs. The accurate and timely diagnosis of malaria infection in NHPs facilitates the appropriate treatment of individuals infected with the malaria parasites. Conventional microscopy based on the examination of Giemsa‐stained thick and thin blood films remains the mainstay of laboratory diagnosis of malaria infection because of the high diagnostic sensitivity and specificity and also the capability for Plasmodium species identification and parasite counts. This procedure is recognized as technically difficult and time‐consuming, requiring considerable training to obtain the necessary skills. In the past few years, efforts to replace the traditional but tedious reading of blood films have led to different techniques for the detection of malaria parasites, including fluorescence microscopy, detection of intraleukocytic hemozoin or malaria pigment using automated blood cell analyzers, immunochromatographic rapid diagnostic tests based on malaria antigen detection, and PCR assays. These techniques offer new approaches for diagnosing malaria in NHPs. This review focuses on the available laboratory diagnostic tools for malaria in NHPs.     

Agreement of SpO2, SaO2 and ScO2 in anesthetized cynomolgus monkeys (Macaca fascicularis)

Objective To assess the agreement between three measurements of arterial oxygen saturation (SpO₂, SaO₂ and ScO₂) in anesthetized cynomolgus monkeys. Study Design Prospective study. Animals Eleven mature, male cynomolgus monkeys (Macaca fasicularis). Methods Monkeys were anesthetized with intramuscular ketamine followed by intravenous propofol. The trachea of each was intubated and the lungs ventilated. Arterial oxygen saturation was measured with a Nonin 8500 V pulse oximeter, using a lingual clip on the cheek. Arterial blood samples were taken from an indwelling catheter. Inspired oxygen concentration was varied from 12 to 20%, and 88 paired arterial blood samples and saturation measurements were taken. Arterial oxygen saturation in the blood samples was measured using a cooximeter. The saturation was also calculated from the arterial oxygen tension using the Adair equation. The results were compared using Bland and Altman's method. Results The pulse oximeter readings were 2.7% higher than that of the cooximeter, with a limit of agreement of ?3.9 to 9.3%. The pulse oximeter readings were 1.8% higher than the calculated saturation, with a limit of agreement of ?6.5% to 10.1%. The cooximeter readings were 0.9% lower than the calculated saturation, with a limit of agreement of ?5.6% to 3.8%. Conclusions The agreement between SpO₂ and other measurements of arterial oxygen saturation in this study is typical for this technique. The bias and limits of agreement are consistent with reports in other species. Clinical relevance The Nonin 8500 V is a useful pulse oximeter for clinical use in primates.     

Effective use of the TSPY gene‐specific copy number in determining fetal DNA in the maternal blood of cynomolgus monkeys

Since the available concentration of single‐copy fetal genes in maternal blood DNA is sometimes lower than detection limits by PCR methods, the development of specific and quantitative PCR detection methods for fetal DNA in maternal blood is anticipated, which may broaden the methods that can be used to monitor pregnancy. We used the TaqMan qPCR amplification for DYS14 multi‐copy sequence and the SRY gene in maternal blood plasma (cell‐free DNA) and fractional precipitated blood cells (cellular DNA) from individual cynomolgus monkeys at 22 weeks of pregnancy. The availability of cell‐free fetal DNA was higher in maternal blood plasma than that of cellular DNA from fractional precipitated blood cells. There was a significantly higher (P < 0.001) mean copy number of fetal male DYS14 from maternal plasma (4.4 × 10⁴ copies/mL) than that of detected fetal cellular DNA from fractional blood cell pellets. The sensitivity of the DYS14 PCR assay was found to be higher than that of the SRY assay for the detection of fetal DNA when its presence was at a minimum. The DYS14 assay is an improved method for quantifying male fetal DNA in circulating maternal blood in the primate model.     

ENDOMETRIOSIS AND A PARAOVARIAN CYST IN A RHESUS MACAQUE

We describe endometriosis in an aged rhesus macaque. There was a large mass and a related paraovarian cyst, typical of the disease. Endometriosis is a common finding in nonhuman primate. In this report, we also review the pathophysiology of the disease and summarize the historical and more recent relevant literature. Given the frequency of endometriosis in the rhesus monkey and the long-life spans (15-30 years) of nonhuman primates in captivity, endometriosis should be suspected in animals displaying the earliest signs of the disease: anorexia, dysmenorrhea, menorrhagia, irregular menstrual cycles, or infertility. Despite recent advances in the diagnosis and therapeutic strategies for endometriosis in women, the disease remains a significant cause of morbidity and ultimately, a cause of mortality, in the older nonhuman primate.     

Hypnotic effects and pharmacokinetics of a single bolus dose of propofol in Japanese macaques (Macaca fuscata fuscata). [corrected

ObjectiveTo describe the hypnotic effects of a single bolus dose of propofol in Japanese macaques, and to develop a pharmacokinetic model.Study designProspective experimental trial.AnimalsFour male macaques (5-6 years old, 8.0-11.2 kg).MethodsThe macaque was restrained and 8 mg kg^?1 of propofol was administrated intravenously at 6 mg kg^?1 minute^?1. Behavioural changes without stimuli (first experiment) then responses to external stimuli (the second experiment) were assessed every 2 minutes for 20 minutes. Venous blood samples were collected before and at 1, 5, 15, 30, 60, 120 and 210 minutes after drug administration, and plasma concentrations of propofol were measured (third experiment). Pharmacokinetic modelling was performed using NONMEM VI.ResultsMacaques were recumbent without voluntary movement for a mean 14.0 ± 2.7 SD (range 10.5-16.2) or 10.0 ± 3.4 (7.2-14.5) minutes and recovered to behave as pre-administration by 25.1 ± 3.6 (22.1-30.1) or 22.2 ± 1.5 (21.1-24.3) minutes after the end of propofol administration without or with stimuli, respectively. Respiratory and heart rates were stable throughout the experiments (28-68 breaths minute^?1 and 72-144 beats minute^?1, respectively). Our final pharmacokinetic model included three compartments and well described the plasma concentration of propofol. The population pharmacokinetic parameters were: V₁ = 10.4 L, V₂=8.38 L, V₃=72.7 L, CL₁= 0.442 L minute^?1, CL₂= 1.14 L minute^?1, CL₃= 0.313 L minute^?1, (the volumes of distribution and the clearances for the central, rapid and slow peripheral compartments, respectively).ConclusionsIntravenous administration of propofol (8 mg kg^?1) at 6 mg kg^?1 minute^?1 to Japanese macaques had a hypnotic effect lasting more than 7 minutes. A three-compartment model described propofol plasma concentrations over more than 3 hours.Clinical relevanceThe developed pharmacokinetic parameters may enable simulations of administration protocols to maintain adequate plasma concentration of propofol.     

Usefulness of cardiac hormones for evaluating valvular disease in cynomolgus monkeys (Macaca fascicularis)

Nonhuman primates are commonly used as experimental animals due to their biological resemblance to humans. In patients with cardiac disease, the levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) tend to increase in response to cardiac damage, and they are thus used as indicators for the diagnosis of human heart failure. However, no reference values for ANP and BNP have been reported for heart disease in nonhuman primates. In this study, we recorded the age, sex, and body weight of 202 cynomolgus monkeys, and performed evaluations to assess the ANP and BNP levels, electrocardiography and echocardiography, and accordingly divided the monkeys into two groups: healthy monkeys and those with spontaneous cardiac disease. Statistical analysis was performed to determine the relationship of ANP and BNP with the factors of age, sex, and body weight. No significant relationship was found between the levels of ANP and BNP and the factors of age, sex, and body weight. However, both the ANP and BNP levels were significantly different between the healthy monkeys and monkeys with valvular disease. Similar to humans, the ANP and BNP levels tended to increase with the progression of cardiac disease in monkeys. Based on these results, we concluded that ANP and BNP are indicators of cardiac disease in nonhuman primates, and that this nonhuman primate cardiac disease model is applicable for cardiology research in humans.