Space efficient system for small animal, whole body microwave exposure at 1.6 GHz

A space efficient, whole body microwave exposure system for unrestrained laboratory animals utilizing a flared parallel plate waveguide is described. The system comprises an Iridium wireless signal source, signal generator, power supply and amplifier (400 W), a coax to waveguide transition, an open ended, flared parallel plate waveguide, and animal exposure area with a dipole field sensing antenna. Across the waveguide aperture the system provides uniform exposure (+/-3 dB incident RF power density) for small animals (rats, mice or hamsters) in up to 18 standard cages for housing groups of animals. Overall system dimensions are 3.6 m (d)x2.4 m (w)x1.6 m (h). Operating at 1.62 GHz, the system provided average power density of 3.7 W/m(2) in the cage area, resulting in a calculated whole body dose of 0.07 W/kg and a calculated average brain dose of 0.19 W/kg.     

Metabolic and vasomotor responses of rhesus monkeys exposed to 225-MHz radiofrequency energy

A previous study showed a substantial increase in the colonic temperature of rhesus monkeys (Macaca mulatta) exposed to radiofrequency (RF) fields at a frequency near whole-body resonance and specific absorption rates (SAR) of 2-3 W/kg. The present experiments were conducted to determine the metabolic and vasomotor responses during exposures to similar RF fields. We exposed five adult male rhesus monkeys to 225 MHz radiation (E orientation) in an anechoic chamber. Oxygen consumption and carbon dioxide production were measured before, during, and after RF exposure. Colonic, tail and leg skin temperatures were continuously monitored with RF-nonperturbing probes. The monkeys were irradiated at two carefully-controlled ambient temperatures, either cool (20 degrees C) or thermoneutral (26 degrees C). Power densities ranged from 0 (sham) to 10.0 mW/cm2 with an average whole-body SAR of 0.285 (W/kg)/(mW/cm2). We used two experimental protocols, each of which began with a 120-min pre-exposure equilibration period. One protocol involved repetitive 10-min RF exposures at successively higher power densities with a recovery period between exposures. In the second protocol, a 120-min RF exposure permitted the measurement of steady-state thermoregulatory responses. Metabolic and vasomotor adjustments in the rhesus monkey exposed to 225 MHz occurred during brief or sustained exposures at SARs at or above 1.4 W/kg. The SAR required to produce a given response varied with ambient temperature. Metabolic and vasomotor responses were coordinated effectively to produce a stable deep body temperature. The results show that the thermoregulatory response of the rhesus monkey to an RF exposure at a resonant frequency limits storage of heat in the body. However, substantial increases in colonic temperature were not prevented by such responses, even in a cool environment.     

Time budget of caged rhesus monkeys exposed to a companion,a PVC perch,and a piece of wood for an extended time

The present investigation assesses the percentage of time that rhesus monkeys (Macaca mulatta) are kept occupied by a more complex cage environment. Sixty animals were continuously exposed for at least 1.5 years to a compatible companion for social interaction, a suspended plastic pipe for perching, and a branch segment for gnawing. The behavior of the partners of each pair was recorded for 60 minutes when the animals were not distracted by human activities. Individuals spent an average of 23.5% of the time interacting with the companion, but only 10.4% with the plastic pipe and 4.8% with the branch segment. Differences were statistically significant. Females were socially more active than males. Subadult animals (3.5–4 years) used both inanimate objects significantly more than did adult animals (9–30 years). It was concluded that (1) a compatible companion, a suspended plastic pipe, and a loose branch segment remain effective stimuli for caged rhesus monkeys after more than 1 year of exposure and (2) a compatible companion is of greater stimulatory value–particularly for adults–than are inanimate objects.     

Acute restraint device for rhesus monkeys

A practical and inexpensive alternative to the standard primate chair is described. The apparatus is designed to allow easy removal of rhesus monkeys from their home cages and to allow restraint without anesthesia. A portable Plexiglas cage, which can be adjusted to accommodate rhesus monkeys of varying sizes, is placed against an animal's home cage. The animal is then trained to avoid the squeeze mechanism of the home cage by going into the Plexiglas cage. The animal's head can then be secured by means of poles hooked to a light weight collar worn permanently. This device and procedure allows an investigator to work with a restrained animal without resorting to drugs, unnecessary force or chronic restraint. Animals can be transferred daily with this technique with minimal conditioning and cooperation.     

Systems for exposing mice to 2,450-MHz electromagnetic fields

Two systems for exposing mice to 2,450-MHz electromagnetic fields are described. In a waveguide system, four mice were placed in a Styrofoam cage and exposed dorsally to circularly polarized electromagnetic fields. The temperature and humidity in the mouse holder were kept constant by forced-air ventilation. For 1-W input power to the waveguide, the average specific absorption rate (SAR) was determined by twin-well calorimetry to be 3.60 ± 0.11 (SE) W/kg in 27-g mice. The maximum SAR at the skin surface determined thermographically was 8.36 W/kg in the head of the mouse. The second system was a miniature anechoic chamber. Six mice were irradiated dorsally to far field plane waves. Copper shielding and high-temperature absorbing material were lined inside the chamber to accommodate the high input power. The air ventilation at the location of the mice was separately controlled so that any heating in the absorber would not affect the animals. For 1-W input power, the average SAR was 0.17 ± 0.01 W/kg and the maximum SAR at the skin surface was 0.41 W/kg in the animal when irradiated with body axis parallel to the E field; the SARs were 0.11 ± 0.01 W/kg and 0.64 W/kg, respectively, when irradiated perpendicular to the E field.     

Possible modulation of N-methyl-D,L-aspartic acid induced prolactin release by testicular steroids in the adult male rhesus monkey

N-methyl-D,L-aspartic acid (NMA), an agonist of the neurotransmitter glutamate has been shown to acutely stimulate the release of prolactin (PRL) in intact rats and monkeys. To further investigate the role of neuroexcitatory amino acids in PRL secretion, the effects of NMA administration were examined on PRL release in long term orchidectomized adult rhesus monkeys, in both the absence and presence of testosterone. Intact and long term castrated adult male monkeys weighing between 8-13 kg, were implanted with a catheter via the saphenous vein for blood withdrawal and drug infusion. Blood samples were collected at 10 min intervals for 50 min before and 70 min after administration of the drug or vehicle. Plasma PRL concentrations were estimated using radioimmunoassay. Whereas a single iv injection of NMA (15 mg/kg BW) induced a prompt discharge of PRL in intact monkeys, an identical dose had surprisingly no effect on PRL secretion in orchidectomized animals. On the other hand, plasma PRL increases in response to a challenge dose of thyrotropin releasing hormone (TRH; 6 micrograms/kg BW, iv) were similar in magnitude in the two groups of monkeys. Testosterone replacement in orchidectomized animals by parenteral administration of testosterone enanthate (200 mg/wk) reinitiated the PRL responsiveness to acute NMA stimulation. These results indicate that N-methyl-D-aspartic acid (NMDA) dependent drive to PRL release in the adult male rhesus monkey may be overtly influenced by the sex steroid milieu.     

The efficacy of diazepam treatment for the management of acute wounding episodes in captive rhesus macaques

The spontaneous development of self-injurious behavior (SIB) in singly housed monkeys poses a challenge for their management and well-being in captivity. Relatively little information is available on effective treatments for SIB. This study examined the effects of diazepam (Valium) on self-wounding and other abnormal behaviors in eight individually housed male rhesus monkeys (Macaca mulatta). Each monkey's response to an anxiolytic dose of diazepam (1 mg/kg or greater orally) was compared with the animal's behavior during drug-free periods. When examined across all animals, treatment with diazepam did not significantly alter wounding frequency or rates of self-directed biting without wounding. However, closer examination of the data revealed that four of the animals showed significant decreases in self-biting and wounding frequency (positive responders, PR group), whereas the remaining monkeys showed a trend towards increased wounding frequency (negative responders, NR group). Subsequent examination of colony and veterinary records demonstrated that compared with NR monkeys, PR monkeys had spent significantly more years in individual cage housing and had experienced a greater number of minor veterinary procedures. PR animals also were significantly less likely to have a documented history of self-biting behavior. Our findings suggest that SIB is not a homogeneous disorder in rhesus monkeys; rather, distinct subtypes exist that require different treatment approaches.     

Voluntary progression order in captive rhesus macaques

The sequence in which 14 laboratory rhesus macaques left their home enclosure during a routine catching procedure was recorded on 30 occasions during 6 weeks. The animals were trained to voluntarily exit one by one and enter a transport cage for weighing and/or treatment. Mean weekly exit orders cross-correlated significantly, and individuals retained their exit positions with remarkable consistency throughout the study period. An animal's position did not depend on its sex, age, or dominance rank. The oldest female never failed to enter the transport cage as number 1. When she was prevented from taking the lead, the group was hesitant but eventually proceeded in the usual order. Food was a strong, yet not absolute, incentive for the monkeys to cooperate. If they could not expect a reward, they took more time before proceeding, but did so in the habitual order. The predictability of the exit sequence has practical managerial value because it makes it possible for a single person to quickly catch a selected group member when necessary.     

Dosimetry evaluation of a cylindrical waveguide chamber for unrestrained small rodents at 1.9 GHz

An exposure system, consisting of four identical cylindrical waveguide chambers, was developed for studying the effects of radiofrequency (RF) energy on laboratory mice at a frequency of 1.9 GHz. The chamber was characterized for RF dose rate as a function of animal body mass and dose rate variations due to animal movement in the cage. Dose rates were quantified in terms of whole‐body average (WBA) specific absorption rate (SAR), brain average (BA) SAR and peak spatial‐average (PSA) SAR using measurement and computational methods. Measurements were conducted on mouse cadavers in a multitude of possible postures and positions to evaluate the variations of WBA‐SAR and its upper and lower bounds, while computations utilizing the finite‐difference time‐domain method together with a heterogeneous mouse model were performed to determine variations in BA‐SAR and the ratio of PSA‐SAR to WBA‐SAR. Measured WBA‐SAR variations were found to be within the ranges of 9–23.5 W/kg and 5.2–13.8 W/kg per 1 W incident power for 20 and 40 g mice, respectively. Computed BA‐SAR variations were within the ranges of 3.2–10.1 W/kg and 3.3–9.2 W/kg per 1 W incident power for 25 and 30 g mouse models, respectively. Ratios of PSA‐SAR to WBA‐SAR, averaged over 0.5 mg and 5 mg tissue volumes, were observed to be within the ranges of 6–15 and 4–10, respectively. Bioelectromagnetics 33:575–584, 2012. © 2012 Wiley Periodicals, Inc.     

Effects of GSM-900 microwaves on the experimental allergic encephalomyelitis (EAE) rat model of multiple sclerosis

The effects of acute exposure to GSM-900 microwaves (900 MHz, 217 Hz pulse modulation) on the clinical parameters of the acute experimental allergic encephalomyelitis (EAE) model in rats were investigated in two independent experiments: rats were either habituated or nonhabituated to the exposure restrainers. EAE was induced with a mixture of myelin basic protein and Mycobacterium tuberculosis. Female Lewis rats were divided into cage control, sham exposed, and two groups exposed either at 1.5 or 6.0 W/kg local specific absorption rate (SAR averaged over the brain) using a loop antenna placed over their heads. There was no effect of a 21 day exposure (2 h/day) on the onset, duration, and termination of the EAE crisis.     

Impact of a privacy panel on the behavior of caged female rhesus monkeys living in pairs

Thirty paired female rhesus monkeys were tested in a control situation when companions had no privacy, and in an experimental situation when they were offered the option to move behind a panel and be alone. Paired partners spent significantly more time in close proximity (same half of the cage) when the privacy panel was provided (means with panel = 76.0%/h vs. means no panel = 60.8%/h; p less than 0.005). At the same time, they were more engaged in affiliative interactions (means with panel = 37.4%/h vs. means no panel = 26.5%/h; p less than 0.025) while the incidence of agonistic interactions tended to decrease (means with panel = 0.3/h vs. means no panel = 2.2/h; p less than 0.1). It was concluded that rhesus monkeys have a need for companionship. They prefer to stay in close proximity with a compatible partner even though this may reduce their available cage space. It was further concluded that companions have no need for prolonged periods of visual seclusion, but occasional privacy is beneficial for their relationship.     

Plasmodium cynomolgi: gametocytocidal activity of the anti-malarial compound CDRI 80/53 (elubaquine) in rhesus monkeys

The gametocytocidal action of a new enamine analogue of primaquine, elubaquine (compound CDRI 80/53, bulaquine), has been evaluated against Plasmodium cynomolgi B in rhesus monkeys. Colony bred Anopheles stephensi mosquitoes were fed on gametocyte carrying rhesus monkeys prior to and at varying intervals after oral administration of a single dose of elubaquine at doses ranging between 0.63 and 5.00 mg/kg. Complete loss of oocyst development and mosquito infectivity was observed within 24 h after administering a single 1.25 mg/kg dose, while higher dose of 3.75 mg/kg inhibited oocyst development within 5 h, indicating gametocytocidal action of the compound. Elubaquine did not show any action against developing oocysts in the vector.     

Fetotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for rhesus macaques (Macaca mulatta)

The fetotoxic and teratogenic potential of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for rhesus macaques (Macaca mulatta) was tested through oral administration to monkeys early in pregnancy. A single or divided dose, 1 μg of TCDD/kg of body weight, was followed by abortion in 13 of 16 pregnant monkeys treated between days 20 and 40 of gestation. One of four aborted at 0.2 μg/kg, and two of two at 5 μg/kg. None of the mothers given 0.2 μg/kg showed signs of toxicity. Eight of the monkeys aborting at 1 μg/kg showed clinical toxicity 44 to 111 days after aborting, and three died. Both given 5 μg/kg became toxic soon after abortion and died. No malformations except for two minor palatal abnormalities of questionable significance were found in the six fetuses that were not aborted at doses of 0.2 and 1.0 μg/kg. These results indicate (1) that TCDD is fetotoxic at doses that frequently have delayed toxicity to the mother, but that conclusions about teratogenicity cannot be drawn, and (2) that pregnant rhesus females are more sensitive to the toxic effects of TCDD than any species tested but the guinea pig.     

Isolation,identification of Streptococcus pneumoniae from infected rhesus monkeys and control efficacy

Background Streptococcus pneumoniae can cause a wide variety of illnesses. Primate animals can be infected by the pneumococcus. A disease occurred among rhesus monkeys in winter 2006. Methods Routine clinical observation, necropsies, bacteriological examinations were conducted, and PCR, pathogenicity to BALB/c mice and antibiotic susceptibility test were examined additionally. Results We conclude that the agent is S. pneumoniae. Based on the antibiotic susceptibility test, a dose of 20 mg/kg body weight daily of Erythromycin was given intramuscular injection for 5 days, resulting in the disappearance of clinical signs, and no newly case reappear be observed till today. Conclusions Therefore, it is suggested that the outbreak of respiratory disease in the rhesus monkeys was because of transmission of S. pneumoniae among rhesus monkeys. The antibiotic therapy finding underscores the utility of Erythromycin to cure the infected rhesus monkeys without causing side effects and without contributing to the further development of antibiotic resistance.     

The influence of day-night cycles and the additive effects of methamphetamine and illumination on the spontaneous activity in rhesus monkeys (Macaca mulatta)

The spontaneous activity of rhesus monkeys in a cage situation was measured under 12 hr. day-night cycles in Exp. I. Without exception, all the subjects (n=10) proved to be more active in the daytime than at night. In Exp. II the effect of methamphetamine upon spontaneous activity was investigated in light and dark conditions. It is supposed in the present study that methamphetamine and illumination raise the arousal level of the subjects and increase their spontaneous activity. The results show that the spontaneous activity of rhesus monkeys, which are thought to be visually dominant, greatly depends on illumination. That is, rhesus monkeys move around well in light conditions but little in dark conditions. Methamphetamine increases spontaneous activity, however, in dark as well as in light conditions. Interaction between methamphetamine and illumination effects was not significant. It would appear from these results that both internal and external factors—methamphetamine and illumination—feed into a common pool of the arousal level which controls spontaneous activity.     

多囊卵巢综合征猕猴的生殖特性(英文)

多囊卵巢综合征(PCOS)是临床上常见的一种内分泌失调性疾病,也是造成无排卵性不孕的重要原因。对多囊卵巢综合征动物模型的研究有10余年,迄今尚未建立起较为理想的模型动物。该研究的目的在于构建猕猴多囊卵巢综合征动物模型,并分析该模型动物的一些主要生殖特性。将6只成年雌性猕猴(6～10a)平均分成2组:PCOS模型组和对照组。模型组动物的建立方法是:在月经周期的第1、3、5天,分别皮下注射丙酸睾丸酮一次,剂量为3.5mg/kg体重;接着在第7、9、11天,分别肌注人绒毛膜促性腺激素一次,剂量是350IU/kg体重;连续注射2个月经周期。对照组动物注射生理盐水。结果显示:PCOS模型组动物呈现出高血清LH和T,分别为(5.35±0.17)IU/L和(7.58±0.14)ng/mL,而且血清LH/FSH值(5.35/1.30=4.12);模型组动物血清FSH、E2和P的含量与对照组无显著差异。腹部B超扫描结果提示,模型组动物卵巢多囊化。对两组动物进行超排处理后,模型组动物卵巢呈明显的过刺激现象,模型组动物胚胎体外培养的囊胚率为23.53%,显著低于对照组(66.67%)(P<0.05),即用丙酸睾丸酮联合人绒毛膜促性腺激素,能够建立PCOS猕猴模型,该模型动物的一些主要生殖特性与人类PCOS相似。     

Pharmacokinetics and Pharmacodynamics of Recombinant Human EPO-Fc Fusion Protein In Vivo

In this study, the in vivo pharmacokinetics and pharmacodynamics of a novel recombinant human erythropoietin (rhEPO) Fc fusion protein, rhEPO-Fc, were studied in both rodents and rhesus monkeys. Animal models of anemia induced by irradiation, cyclophosphamide and partial renal ablation were used to evaluate therapeutic effects of rhEPO-Fc. We have demonstrated that serum half-life of rhEPO-Fc was 29.5 to 38.9 h at doses of 8, 25, 80 µg/kg in rhesus monkeys and 35.5 to 43.5 h at doses of 16, 50, 160 µg/kg in rats. In anemia animal models, rhEPO-Fc dose-dependently (7.5–30.0 µg/kg in mice, 5.4–21.4 µg/kg in rats and 5.0–10.0 µg/kg in rhesus monkeys) increased reticulocyte level, followed by an increase of RBC count, hemoglobin and hematocrit levels. At reduced intervention frequency of weekly treatments, rhEPO-Fc showed similar hematopoietic effects as compared with rhEPO given three times a week. These results indicated that rhEPO-Fc could potentially be used in treatment of anemia and warrants future clinical trials.     

Hormonal response to restraint in rhesus monkeys

Abstract: The purpose of this study was to characterize the hormonal responses to a restraining system in four adult male rhesus monkeys (Macaca mulatta) in preparation for a spaceflight project. After the monkeys were accustomed to food and water (Phase I), blood-volume-regulating hormones were measured during three phases: 10 days in a metabolic cage (Phase II), 16 days sitting in a restrained position in a specially designed metabolism chair (Phase III) and 10 days in metabolic cage (Phase IV). An increase of active renin (30%) and vasopressin (25%) was observed at the end of Phase III. A decrease of atrial natriuretic peptide (ANP), urodilatin, and sodium excretion occurred during the first days of Phase III. Catecholamines were unchanged. A dramatic increase (tenfold) in urinary excretion of growth hormone occurred during all of Phase III and at the beginning of Phase IV. These findings are similar to those found in man during isolation inactivity and during confinement stress.     

Embryotoxicity of sex steroidal hormones in nonhuman primates: II. Hydroxyprogesterone caproate, estradiol valerate

Two sex steroid compounds which have been used clinically for parenteral supportive therapy of pregnancy were examined for embryotoxic effects in rhesus and cynomolgus macaques. Hydroxyprogesterone caproate (HPC) alone or in combination with estradiol valerate (EV) were administered intramuscularly (i.m.) to pregnant monkeys at 7-day intervals between 20 and 146 days of gestation and fetuses were examined following cesarean section at 150 +/- 2 days. HPC alone was tested in both species at doses ranging from 0.01 X to 10 X the human dose equivalent (HDE); only rhesus monkeys were exposed to the HPC + EV combination at 0.1 X to 10 X HDE. Total embryolethality resulted following the administration of HPC alone and combined with EV at 1 X and 10 X HDE in rhesus monkeys; the level of abortions in cynomolgus monkeys exposed to HPC (0.1 X to 1 X HDE) was comparable to controls. A small number of nonspecific malformations and developmental variations observed in cynomolgus fetuses after HPC exposure were considered to be incidental findings. No anomalies were found in surviving rhesus monkey fetuses treated with HPC + EV. The results indicate that long-term in utero exposure to the progestin, HPC, alone or in combination with EV in rhesus and cynomolgus monkeys, is embryolethal but not teratogenic at doses up to ten times the human therapeutic dose.     

Thyroid status of female rhesus monkeys and preliminary information on impact of perchlorate administration

Thyroid status was assessed in adult female rhesus monkey breeders at the California National Primate Research Center at the beginning of the breeding season. The 95% confidence intervals for thyrotropin (TSH), thyroxine (T(4)) and triiodothyronine (T(3)) (n = 66-80) were similar to those previously reported in smaller samples of macaque monkeys. Based on human criteria, 10 of 80 monkeys (12%) were hypothyroid (TSH > 2.0 μIU/mL). Because hypothyroxinaemia can be a risk factor in pregnancy, T(4) status was compared with past breeding history, breeding outcome for that season and general health records in a subset of 42 breeders. Age, weight and parity did not differ between monkeys in the lowest T(4) quartile as compared with those in the upper three quartiles. However, T(4) concentrations were significantly associated with the number of missed menstrual cycles during the previous breeding season. In additional work, three healthy lactating rhesus monkeys were given three different doses of environmental contaminant and thyroid iodine uptake inhibitor, ammonium perchlorate (0.006, 0.34, 12.8 mg/kg/day, respectively) in food for two weeks. Thyroid status variables (TSH, T(4), T(3), thyroid radioactive iodine uptake) were then measured. In the monkey receiving the highest perchlorate dose, iodine uptake was suppressed relative to baseline. The study shows the availability of tools to study thyroid status in rhesus monkeys, the variability of thyroid status in the breeder colony and the potential ability of environmental factors to influence thyroid status.