The Rhesus Macaque (Macaca mulatta) Sperm Proteome

Mass spectrometry based proteomics has facilitated sperm composition studies in several mammalian species but no studies have been undertaken in non-human primate species. Here we report the analysis of the 1247 proteins that comprise the Rhesus macaque (Macaca mulatta) sperm proteome (termed the MacSP). Comparative analysis with previously characterized mouse and human sperm proteomes reveals substantial levels of orthology (47% and 40% respectively) and widespread overlap of functional categories based on Gene Ontology analyses. Approximately 10% of macaque sperm genes (113/1247) are significantly under-expressed in the testis as compared with other tissues, which may reflect proteins specifically acquired during epididymal maturation. Phylogenetic and genomic analyses of three MacSP ADAMs (A-Disintegrin and Metalloprotease proteins), ADAM18-, 20- and 21-like, provides empirical support for sperm genes functioning in non-human primate taxa which have been subsequently lost in the lineages leading to humans. The MacSP contains proteasome proteins of the 20S core subunit, the 19S proteasome activator complex and an alternate proteasome activator PA200, raising the possibility that proteasome activity is present in mature sperm. Robust empirical characterization of the Rhesus sperm proteome should greatly expand the possibility for targeted molecular studies of spermatogenesis and fertilization in a commonly used model species for human infertility.The application of mass spectrometry (MS) based proteomics, coupled with whole genome annotation of an increasing number of species, has greatly extended our knowledge of sperm composition. Traditional methods used to assess sperm composition, including the use of sperm-specific antibodies and 2D gel electrophoresis, have identified a limited number of sperm proteins. These traditional studies have been augmented in recent years by the use of high throughput and highly sensitive MS (shotgun proteomics) that have substantially increased the accuracy of peptide identification, resulting in a significant increase in proteome coverage. Indeed, advances in MS instrumentation, data acquisition, and the availability of genome annotations have, for example, increased sperm proteome coverage in Drosophila from 381 (1) to 1108 proteins (2) over a five year period.Two main MS based methodologies have been applied to study sperm composition, including (i) 2D PAGE followed by spot excision and MS and (ii) digestion of proteins, followed by MS/MS analysis of the resulting peptides (3). Although each method has its own advantages and disadvantages, a far greater level of proteome coverage is obtained using MS/MS (4). A previous comparative study found that each method identified proteins not found in the other and vice versa, and therefore it has been suggested that these methods should be used to complement each other (5). Thus, although no single methodology yet exists capable of producing a complete whole cell proteome, MS/MS methods provide deeper and broader coverage and are therefore the current method of choice. Shotgun proteomics has characterized sperm proteomes in a variety of taxa including plants, invertebrates and mammals such as human, mouse, rat, and bull (3, 6–11). These studies achieve varying levels of proteome coverage as a result of several factors including the choice of MS equipment, sample acquisition, purification, solublization, and fractionation schemes. Although these different approaches make direct comparisons difficult they nevertheless have provided invaluable information regarding the composition of sperm and have helped to identify novel proteins that play important roles in sperm function and reproduction.In this study we use MS based proteomics to elucidate the sperm proteome of a species of old world monkey, the Rhesus macaque (Macaca mulatta). Due primarily to their genetic and physiological similarities to humans, Rhesus macaques are the most widely used nonhuman primate model system for basic and applied biomedical research (12). Rhesus macaques are also used extensively as a model of human reproduction where numerous similarities at the molecular level have been observed between gametes of the two species, and why Rhesus macaques have become a useful model system for fertility and assisted reproductive technology research (13). A more complete knowledge of the sperm proteome will facilitate reproductive studies using the Rhesus macaque as a model organism. However, despite its widespread use in reproductive biology, the macaque sperm proteome (MacSP)¹ has yet to be characterized.Although insight into the MacSP will facilitate reproductive studies using the Rhesus macaque as a model organism, this knowledge can also be used to better understand the composition of human sperm. Sperm mature and gain fertilization competency as they traverse the epididymis, a specialized duct that connects the testis to the vas deferens (14). During the maturation process, sperm lose or modify a number of their surface proteins and gain additional transient or permanent surface proteins in a well-organized manner, and it is only after emerging from the cauda epididymis that sperm are motile and considered fertilization competent (14, 15).Proteomic studies of human sperm have been undertaken (3, 6, 10), identifying between 98–1760 sperm proteins, however these studies used sperm from ejaculates which complicates sperm proteome analysis. A previous study identified 923 proteins present in human seminal plasma (16), which is likely to be only a fraction of the seminal plasma proteome. Human sperm proteome data sets derived from human ejaculates makes it difficult to differentiate which of the identified proteins are sperm or seminal plasma constituents. For example, a major seminal protein family, the semenogelins are not expressed in the testis but are found in sperm proteomes determined from ejaculates (6, 10). Such highly abundant seminal proteins may mask lower abundance integral sperm proteins and inhibit their identification by MS. In order to avoid these problems, we collected mature sperm directly from the cauda epididymis of the Rhesus macaque, thus avoiding contamination from seminal plasma proteins.In the present study, sperm proteins were separated using 1D SDS-PAGE, digested and the resulting peptides analyzed by LC MS/MS. Using high stringency parameters for peptide identification, we conservatively identified 1247 proteins from purified samples of Rhesus macaque sperm. Given their close evolutionary relationship, the Rhesus macaque and human share 93% nucleotide homology (12). Data from this study can be used to complement what is currently known about the composition of human sperm and provides a more useful proxy of human sperm proteome composition than the proteomes of other non-primate mammals for which data is available. Studies of sperm composition, especially those in human, can be applied to develop novel molecular based clinical diagnostic tests of sperm quality, which is currently limited to evaluating parameters such as sperm count, morphology and motility. In addition, knowledge of sperm components can lead to the discovery of novel contraceptives and infertility treatments.     

实验恒河猴超声心动图的初步研究

分别采用二维、脉冲多普勒及M型超声心动图Teichholtz公式对1 0只健康成年实验恒河猴(Macacamulatta)的心脏结构、心脏血流动力学及左室收缩功能进行测定,并比较不同性别间各参数的差异,以建立正常健康成年恒河猴超声心动图相关生理学参数的基础正常值。结果表明,健康成年实验恒河猴超声心动图各项生理指标类似于人类新生儿的指标,雌、雄组间比较除室间隔舒张末期厚度有统计学差异外(P <0 0 5 ) ,其余指标均无统计学差异(P >0 0 5 )。     

Mineralized Trichobezoars in a Rhesus Macaque (Macaca mulatta)

A five-year-old female rhesus macaque (Macaca mulatta) presented with a thin body condition and multiple palpable mid-abdominal masses. Mineralized cecal trichobezoars were removed surgically. Thirteen months later, similar masses recurred and were confirmed with radiographs. This is the first case report of a mineralized cecal trichobezoar in a rhesus macaque.     

MamuSNP: a resource for Rhesus Macaque (Macaca mulatta) genomics

We developed a novel method for identifying SNPs widely distributed throughout the coding and non-coding regions of a genome. The method uses large-scale parallel pyrosequencing technology in combination with bioinformatics tools. We used this method to generate approximately 23,000 candidate SNPs throughout the Macaca mulatta genome. We estimate that over 60% of the SNPs will be of high frequency and useful for mapping QTLs, genetic management, and studies of individual relatedness, whereas other less frequent SNPs may be useful as population specific markers for ancestry identification. We have created a web resource called MamuSNP to view the SNPs and associated information online. This resource will also be useful for researchers using a wide variety of Macaca species in their research.     

Aggressive Play and Communication in Rhesus Monkeys (Macaca mulatta)

One adaptive function that has been suggested for social playin higher primates is the learning, refining, or practicingof communicative skills. Despite the absence of experimentaldata, a comparison of the structure of aggressive play and communicationmay shed light on this hypothesis. The great majority of rhesusmonkey agonistic interactions are mediated by stereotyped signals.Deprivation experiments have shown that appropriate interpretationand use of such signals requires early social experience. Suchexperience seemingly must have the following characteristics:(i) The relevant agonistic signals must occur, (ii) These signalsmust regularly be paired with other stimuli for appropriateresponses to signals to be learned. Signals must produce regularresponses in other monkeys for appropriate use to be learned.Aggressive play seems to be an unpromising context in whichto learn, refine, or practice agonistic signals. These signalsare not observed in play, and the signals that do occur arerestricted to play and are not regularly paired with unconditionedstimuli.     

Intracranial Meningioma with Ophthalmoplegia in a Rhesus Macaque (Macaca mulatta)

A 21-y-old female rhesus macaque presented with signs of internal and external ophthamoplegia, including anisocoria and ptosis. Ophthalmoplegia is the paralysis or weakness of one or more intraocular or extraocular muscles that control the movement of eye; this condition can be caused by neurologic or muscle disorders. The macaque was euthanized due to progression of clinical symptoms, and postmortem gross examination revealed a mass at the base of the brain attached to the meninges. Histopathologic examination led to the diagnosis of intracranial meningioma. Here we describe a case of intracranial meningioma with internal and external ophthalmoplegia in a rhesus macaque (Macaca mulatta).Meningioma is a tumor that develops in the meninges, including the dura mater, arachnoid mater, and pia mater, all of which surround the brain and spinal cord. In humans, meningioma is the most frequently encountered primary intracranial neoplasia and accounts for approximately 35% of all reported primary brain tumors in the United States.^5,7 Clinical manifestations are dependent on the size and location of the tumor.^3,23 To our knowledge, only 3 cases of naturally occurring meningioma in nonhuman primates have been reported; these cases affected 2 baboons and 1 collared brown lemur.^17,19,21 The meningiomas of 2 of these previous cases were described only briefly as part of a disease survey of neoplasia in 100 free-ranging baboons and a captive prosimian population.^17,21 The third report focused on the pathologic features of the meningioma described with no mention of the clinical signs in the baboon, although its location was similar to that of the case we describe here.¹⁹In the current case report, we describe the clinical manifestations, postmortem examination, and diagnosis of an intracranial meningioma in a rhesus macaque (Macaca mulatta).     

Metastatic Hepatocellular Carcinoma in a Juvenile Rhesus Macaque (Macaca mulatta)

Neoplasia in juvenile (younger than 5 y) rhesus macaques has been estimated to represent only approximately 1.4% of all occurrences of spontaneous neoplasia. Here we report an unusual case of a 3.75-y-old primiparous female rhesus macaque that was euthanized due to poor prognosis associated with progressive anemia, marked hepatomegaly, and radiographic evidence of metastatic neoplasia. Postmortem examination revealed an invasive, hemorrhagic hepatic mass that effaced approximately 70% of the liver parenchyma and had evidence of metastatic spread to multiple abdominal organs, the lungs, and the pituitary gland. Neoplastic polygonal cells lined large necrohemorrhagic cavities and exhibited marked anisocytosis and anisokaryosis, with frequent multinucleate cells. There was no desmoplasia associated with the primary neoplasm or metastases. Immunohistochemical studies revealed the neoplastic cells to be diffusely reactive with pancytokeratin, cytokeratin 7, and cytokeratin 8/18 antibodies and rarely reactive with carcinoembryonic antigen antibodies. The cells did not react with vimentin, S100, CD31, or factor VIII antibodies. Tumor morphology and immunophenotype led to the diagnosis of anaplastic hepatocellular carcinoma. This report represents the first known case of metastatic liver neoplasia in a rhesus macaque. The young age of this animal and the aggressive nature of the neoplasm are highly unusual and reminiscent of adolescent onset hepatocellular carcinoma in humans.Abbreviations: CK, cytokeratin; HCC, Hepatocellular carcinomaNeoplasia in juvenile rhesus macaques (Macaca mulatta) is extremely uncommon.^17,18 In a recent review of spontaneous neoplasia in 2 colonies of rhesus macaques, animals younger than 5 y represented only 1.4% of the total number of cases, and primary hepatic tumors were uncommon.¹⁸ All 5 of the cases detected among 2660 macaques involved animals between 14 and 26.8 y of age, and none had evidence of metastasis. Primary hepatic tumors appear to be similarly infrequent occurrences in other nonhuman primates, with the notable exception of prosimians, in which tumors arising from the liver are common spontaneous neoplasms.^3,15,17,18 Malignant liver tumors account for only 1% of pediatric tumors in humans.^5,7,12 Approximately 80% of these are hepatoblastomas—neoplasms arising from liver progenitor cells—and hepatocellular carcinoma (HCC) represents the second most frequent diagnosis.^5,7,12The medicine department of the California National Primate Research Center evaluated a 3.75-y-old, sexually mature, female rhesus macaque for rapidly progressive disease associated with a hepatic mass. Anaplastic HCC with extensive metastasis was diagnosed after postmortem examination. The current report describes the clinical progression of disease, the gross and microscopic pathology of the affected macaque, and the immunohistochemical characterization of the neoplasm.     

Glycosylated Haemoglobin (Hb A1) in Normal Rhesus Monkeys (Macaca mulatta)

Glycosylated haemoglobins were measured in 23 healthy juvenile rhesus monkeys by the use of commercially available minicolumn chromatography (Quick Sep., Isolab Inc., Ohio, USA) to establish the normal range. Values obtained (mean ± 1 standard deviation (SD) 1.57 ± 0.68%) were significantly lower than that of 17 adult healthy human volunteers by the use of the same method of estimation (mean ± 1 SD of 5.34 ± 0.78%).     

A Behavioral Taxonomy of Loneliness in Humans and Rhesus Monkeys (Macaca mulatta)

Social relationships endow health and fitness benefits, but considerable variation exists in the extent to which individuals form and maintain salutary social relationships. The mental and physical health effects of social bonds are more strongly related to perceived isolation (loneliness) than to objective social network characteristics. We sought to develop an animal model to facilitate the experimental analysis of the development of, and the behavioral and biological consequences of, loneliness. In Study 1, using a population-based sample of older adults, we examined how loneliness was influenced both by social network size and by the extent to which individuals believed that their daily social interactions reflected their own choice. Results revealed three distinct clusters of individuals: (i) individuals with large networks who believed they had high choice were lowest in loneliness, (ii) individuals with small social networks who believed they had low choice were highest in loneliness, and (iii) the remaining two groups were intermediate and equivalent in loneliness. In Study 2, a similar three-group structure was identified in two separate samples of adult male rhesus monkeys (Macaca mulatta) living in large social groups: (i) those high in sociability who had complex social interaction with a broad range of social partners (putatively low in loneliness), (ii) those low in sociability who showed tentative interactions with certain classes of social partners (putatively high in loneliness), and (iii) those low in sociability who interacted overall at low levels with a broad range of social partners (putatively low or intermediate in loneliness). This taxonomy in monkeys was validated in subsequent experimental social probe studies. These results suggest that, in highly social nonhuman primate species, some animals may show a mismatch between social interest and social attainment that could serve as a useful animal model for experimental and mechanistic studies of loneliness.     

Intraspecific Variability in Parenting Styles of Rhesus Macaques (Macaca mulatta): The Role of the Social Environment

This study tested the hypothesis that differences in parenting styles between two captive populations of rhesus macaques, one living in the UK (Madingley) and the other in the USA (Yerkes), are associated with differences in the degree to which social interactions with other group members pose a risk to infants. Twenty-eight mother–infant dyads, 17 living at Madingley and 11 at Yerkes, were observed for 24 h during the first 12 wks of infant life. Mother–infant dyads living at Madingley spent a higher percentage of time in contact than those living at Yerkes. The Madingley mothers also restrained and retrieved their infants more often, and rejected them less often than the Yerkes mothers. Consistent with the prediction, the protective parenting style of the Madingley mothers was associated with higher frequency of infant kidnapping and higher risk of infant harassment from other group members. Interpopulation differences in risks to infants and parenting styles are likely to be the result of differences in social density in the two environments rather than differences in the matrilineal structure of the two populations.     

糖在猕猴精子低温冷冻保存过程中的作用

TTE或TEST防冻液在冻存猕猴精子时产生不同结果,其主要不同在于防冻液中糖成分的不同。本实验利用透射电镜技术检测这2种防冻液冻存的猕猴精子冷冻前后超微结构的变化,以说明糖在低温冻存过程中的作用。结果表明,冷冻复苏过程对精子结构产生了影响。TTE法低浊保存的猕猴精子的头部的质膜出现少许皱褶或泡化现象,但精子的顶体、核或是精子尾部的结构与鲜精的结构基本相似。猕猴精子经TEST法低温保存后,大部分精子结构则发生了明显的变化。精子膜、顶体和精子核明显泡化、损伤或破裂,精子尾部不能分辨出正常的超微结构。这提示,可能由于TTE防冻液中复杂的糖成分在降温／复苏过程对精子起到了较好的协同冷冻保护作用;而TEST防冻液中单一的糖成分不能完全保护精子避免低温损伤,低温保存过程破坏了精子的结构,并影响了复苏后精子体外存活能力与受精能力。     

猕猴精子优选及体外获能的研究

选择活率高的精子并进行体外获能是开展猕猴体外受精研究的必要程序, 是研究猕猴受精生物学的重要手段。本实验采用上浮法和Percoll 梯度离心法对猕猴精液进行了优选, 并对处理后的精子形态正常率、精子活率、密度及受精率作了比较, 发现二者差异不显著; 用dbcAMP 和咖啡因使精子获能, 发现只有两种获能剂同时存在才能使猕猴精子获能并使卵母细胞受精。结论为: 上浮法和Percoll 法都是有效的精子优选法, 对受精率的影响差异不显著; dbcAMP 和咖啡因在猕猴精子体外获能时缺一不可。     

Sources of Acoustic Variation in Rhesus Macaque (Macaca mulatta))Vocalizations

All species in the genus Macaca produce a set of harmonically rich vocalizations known as “coos”. Extensive acoustic variation occurs within this call type, a large proportion of which is thought to be associated with different social contexts such as mother-infant separation and the discovery of food. Prior studies of these calls have not taken into account the potential contributions of individual differences and changes in emotional or motivational state. To understand the function of a call and the perceptual salience of different acoustic features, however, it is important to determine the different sources of acoustic variation. I present data on the rhesus macaques' (M. mulatta) coo vocalization and attempt to establish some of the causes of acoustic variation. A large proportion of the variation observed was due to differences between individuals and to putative changes in arousal, not to differences in social context. Specifically, results from a discriminant-function analysis indicated that coo exemplars were accurately assigned to the appropriate individual, but vocal “signatures” were more variable in some contexts than in others. Moreover, vocal signatures may not always be reliable cues to caller identity because closely related individuals sound alike. Rhesus macaque coos evidently provide sufficient acoustic information for individual recognition and possibly kin recognition, but are unlikely to provide sufficient information about an external referent.     

Septicemia in an Indian Rhesus Macaque (Macaca mulatta) associated with Providencia stuartii

Providencia stuartii (P. stuartii) is an opportunistic pathogen and major concern in urinary catheter‐related infections in human medicine. Here we report P. stuartii‐induced septicemia in an eighteen‐year‐old, female India‐origin Rhesus macaque with multiple traumatic wounds. The animal had neutrophilic leukocytosis, necrosuppurative meningoencephalitis, hypophysitis and bronchopneumonia with vasculitis, thrombosis, and clusters of extracellular Gram‐negative bacilli. P. stuartii was isolated from the lesions of the brain and lung and confirmed by PCR and sequencing. To the authors’ knowledge, this is the first case of septicemia associated with P. stuartii in a non‐human primate.     

Meningoencephalitis Due to Listeria monocytogenes in a Pregnant Rhesus Macaque (Macaca mulatta)

We here report a spontaneous case of meningoencephalitis due to Listeria monocytogenes in an adult primiparous rhesus macaque (Macaca mulatta) during an outbreak of listeriosis in an outdoor enclosure. Clinical signs included tremors, abnormal posture, and altered mental status. Hematology and analyses of cerebrospinal fluid were consistent with bacterial infection. Pure cultures of L. monocytogenes were recovered from the placenta–abortus, cerebrospinal fluid, and brain tissue. The macaque did not respond to treatment and was euthanized. Histopathologic examination of the brain revealed acute meningoencephalitis. This case represents an unusual clinical and pathologic presentation of listeriosis in a nonhuman primate in which the dam and fetus both were affected.Listeria monocytogenes is a ubiquitous, facultative anaerobic, intracellular gram-positive coccobacillus. This bacterium is found in diverse environments including (but not limited to) soil, water, plant matter, food items, and the intestinal tract of mammalian hosts.^15,18 The organism is environmentally resistant, being able to survive in dried media for several months and in moist soil for up to a year.¹⁵ L. monocytogenes is the causative agent of listeriosis, a bacterial infection that has a worldwide distribution and affects a wide range of mammals and birds, including human beings.In people, L. monocytogenes is a relatively uncommon foodborne pathogen; its abilities to survive food processing and grow in cold conditions allow it to persist in appropriately stored or refrigerated foods.² In people, listeriosis occurs both sporadically and as large outbreaks,¹⁸ generally comprising 3 separate syndromes with clinical manifestations ranging from mild to life-threatening.³⁵ The most common form is seen in immunocompetent, nonpregnant adults as a febrile gastroenteritis.^2,18,21 The other 2 forms, which occur in fetuses and immunocompromised patients, are more severe.^19,21 In pregnant women, maternal listeriosis is asymptomatic or causes mild, flu-like symptoms, but the bacterium''s ability to cross the placenta and the blood–brain barrier of the fetus results in neonatal septicemia, meningitis, abortion, and stillbirth.¹⁶ In elderly and immunocompromised patients, septicemia and meningoencephalitis are life-threatening manifestations of literiosis.²⁶ The worldwide case fatality rate varies widely among countries, sometimes exceeding 50% despite what is considered to be appropriate antibiotic therapy.¹⁸ In 2009, the Centers for Disease Control reported 524 cases of listeriosis in the United States, which were associated with a 19% resulting in death.⁴In ruminants, listeriosis is also known as ‘circling disease’ and ‘silage disease.’^8,18,21 Foodborne infection with L. monocytogenes is well described, and many studies have shown that spoiled silage may be a source of listeria outbreaks.^8,18 Rhombencephalitis and diffuse meningoencephalitis are the most recognized forms of the infection in ruminants; sporadic abortion is reported also.²² Clinical signs of listeria encephalitis in cattle, sheep, and goats are characterized by unilateral or bilateral brainstem dysfunction and cranial nerve deficits. In sheep and goats, the course of the disease is acute, but the disease in cattle has a more chronic progression, with neurologic manifestations that can last 4 to 14 d.^1,22In rabbits, infection with L. monocytogenes is characterized by abortion in pregnant does or sudden death; neurologic signs are rare.¹ In poultry, an acute form with septicemia and sudden death occurs in adults, in contrast to a subacute–chronic form, with encephalitis, in the young.⁶The literature on L. monocytogenes in nonhuman primates is sparse^5,11,17,33 and more recently limited to experimental infection of pregnant animals. In pregnant rhesus macaques (Macaca mulatta), experimental infection during the last trimester of gestation can cause stillbirth with no other clinical signs.^23,24 In our colony, however, infection with L. monocytogenes is endemic. Every year, several spontaneous abortions or stillbirths in our outdoor colony are caused by infection of the dam with this organism. Culture of L. monocytogenes from both the abortus–fetus and placenta are well documented. As described in the literature,^23,24 the dams in our colony do not demonstrate any clinical signs prior to the abortion or stillbirth.During the winter to spring of 2011, one of our outdoor housing enclosures experienced an outbreak of listeriosis. This outside corral housed 100 rhesus macaques in a social group that included 42 reproductive females. Of these reproductive females, 37 (88%) were confirmed pregnant by abdominal palpation or ultrasonography or both. From January 2011 to May 2011, 19 (51%) stillbirths and neonatal deaths (in infants younger than 3 d) were reported in this enclosure; 13 (68%) of these tissues (placenta, 3; fetal lungs, 8; fetal peritoneum, 2) were culture-positive for L. monocytogenes. In all cases except the one presented here, the dam did not manifest any clinical signs prior to or after the delivery of a stillborn or premature birth with neonatal death.Here we describe an unusual case of listeriosis in a primiparous pregnant female rhesus macaque that manifested severe neurologic impairment and intrautero death of the fetus.     

Brain Abscess in a Rhesus Macaque (Macaca mulatta) with a Cephalic Implant

We report a case of brain abscess after craniotomy and the placement of a recording chamber for electrophysiologic records in an adult rhesus macaque (Macaca mulatta) enrolled in visual research. Approximately 2 wk after surgery, the macaque presented with nonspecific gastrointestinal signs and showed no evidence of fever, neurologic deficits, increased intracranial pressure, suggestive alterations in the CBC, or abnormal changes in the recording chamber. The macaque responded to symptomatic and antibiotic treatment and showed no behavioral or abnormal clinical signs for 3 wk before collapsing suddenly. The macaque was euthanized, and pathologic evaluation revealed a large brain abscess immediately under the original craniotomy.Brain abscess is a serious, potentially fatal condition that can arise from direct implantation of an infectious organism (for example, trauma, wound or surgical complication), local extension from an adjacent structure (for example, infection of the cribriform plate, inner ear, paranasal sinus), or hematogenous spread (usually from a primary site in the heart, lungs or tooth extraction by bacterial embolism).^9,14 In humans, most brain abscesses are due to direct or indirect cranial infection from the paranasal sinus, middle ear, or teeth. An increasing proportion is secondary to head trauma or complications from neurosurgeries, whereas as many as 20% to 30% of cases have no obvious or identified cause.⁶ The condition is relatively uncommon in nonhuman primates because of the lack of foci of infection that can lead to direct extension to the brain.¹⁹ The hematogenous spread of bacteria or fungi is considered the most common route,² whereas brain abscesses from direct implantation of a pathogen are seldom reported in the literature despite the numerous nonhuman primates involved in neuroscience research and undergoing regular electrophysiologic recordings in the brain. Most importantly, a brain abscess can be difficult to diagnose, given its nonspecific and variable presentation in both humans and nonhuman primates.^13,19Here we describe the clinical case of an adult rhesus macaque (Macaca mulatta) involved in neuroscience research who presented with nonspecific gastrointestinal signs 2 wk after cephalic implantation and craniotomy surgery. The macaque responded to symptomatic treatment, but the condition recurred several weeks later and led to acute circulatory shock. During necropsy, the condition was diagnosed as a brain abscess.     

Development of Rhesus Macaque Monkeys (Macaca mulatta) at Early Stages of Ontogenesis at the Artificial Nurturing and Rearing by Human

The experience of the artificial nurturing and rearing of rhesus macaque kids from the moment of their birth to the age of half a year is described. Data are presented about development of sensomotor functions, peculiarities of manifestation of complete forms of the species-specific behavior and communicative response of socially isolated monkeys for the first six months of life at their rearing by human. The obtained results promote enlargement of the biological knowledge of ontogenesis of the lower monkeys.     

Efficacy of Antibiotic-Impregnated Polymethylmethacrylate Beads in a Rhesus Macaque (Macaca mulatta) with Osteomyelitis

Here we describe the successful surgical implementation of antibiotic-impregnated polymethylmethacrylate beads in a rhesus macaque (Macaca mulatta) with marked osteomyelitis. The macaque presented to the veterinary clinic with grossly contaminated bite wounds in the left ankle secondary to conspecific trauma. Radiographic findings were highly suggestive of osteomyelitis. Additional differential diagnoses included bony infarct, fracture, and cellulitis. In light of the location of the lesion and extensive tissue trauma, the animal had a poor prognosis. Systemic, broad-spectrum antibiotics were instituted. After 2 wk of care, lesions did not respond to empirical therapies. On consultation, a veterinary orthopedic surgeon at another facility recommended placement of antibiotic-impregnated polymethylmethacrylate beads at the sites of osteomyelitis. The animal underwent minor surgery in which beads were introduced into the wound. The monkey had a positive response to therapy. The animal regained full function and was returned to outdoor social housing. Veterinarians are encouraged to consider using antibiotic-impregnated polymethylmethacrylate beads when treating osteomyelitis in other nonhuman primates and in other traditional laboratory animal species.Rhesus macaques can be aggressive, and mild to marked trauma can result from agonistic social encounters.⁶ The AAALAC-accredited California National Primate Research Center houses more than 4000 rhesus macaques (Macaca mulatta) in large outdoor social corrals. The incidence of animals presenting to the center''s veterinary hospital with traumas requiring sutures or amputation of digits ranges from 5% to 9% annually. Bite wounds predominate and frequently involve extremities (tail tips and digits). Open wounds place animals at risk for development of acute or chronic infections, including osteomyelitis.^8,9,11,21 Bacterial contaminants reflect the presence of oral flora secondary to characteristic wounding (for example, Bacteroides spp., coagulase-positive Staphlococcus spp., and Eicinella spp.).Clinical management of osteomyelitis is challenging. The standard of care is based on irrigation of the wound, debridement of necrotic tissues, and administration of systemic antibiotics. Efficacy of systemic antibiotic therapy can be compromised due to poor tissue perfusion and compromised vasculature. Regimens for local administration of antibiotics are being developed continually to improve orthopedic wound management.^{5,8,9,11,19,21,24,26} Antibiotic-impregnated polymethylmethacrylate (bone cement) is used in human and veterinary orthopedic surgery to provide high, localized concentrations of antibiotics in high-risk, poorly vascularized wounds.Few cases of osteomyelitis have been reported in nonhuman primates, and even fewer reports reflect successful management of such conditions.^{4,23,25,27,28} Here we document the successful clinical use of antibiotic-impregnated polymethylmethacrylate beads to treat osteomyelitis in a laboratory-housed rhesus macaque.