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Hypothermia and electromagnetic rewarming in the rhesus monkey.

Five male rhesus monkeys (Macaca mulatta) were subjected, under ketamine anesthesia, to repeated hypothermia treatments that produced an average rectal temperature of 28.3 degrees C. Following hypothermia induction, the subjects were rewarmed using either a ventrally applied surgical heating pad supplied with 35 degrees C water or a radio-frequency (RF) induction coil operating at 13.56 MHz with an average specific absorption rate (SAR) calculated to be approximately 5.5 W X kg-1. A special temperature probe, nonperturbing to RF, was used in the RF rewarming experiments. Control experiments were also conducted in which only ketamine was administered over a 3-h period. RF rewarming to 35 degrees C typically required only 50 min; whereas, an average of 137 min was required for heating-pad rewarming. Analyses of blood serum collected during and up to 48 h after hypothermia treatments showed elevations at 24 h in creatine phosphokinase (CPK), lactic dehydrogenase (LDH), and glutamic oxaloacetic transaminase (GOT), and these elevations were highest for the ketamine controls and lowest for the RF rewarming experiments. The subjects have been periodically examined since these experiments, and all appear to be in good health. It is concluded that the careful application of RF energy to the central core of the body can successfully be used for rewarming purposes, is more effective than externally applied rewarming techniques, and is potentially useful in remote locations.

Animals↗

Responses of infant rhesus monkeys to inoculation with Mason-Pfizer monkey virus materials.

Rhesus monkeys neonatally inoculated with Mason-Pfizer monkey virus (M-PMV) and virus-infected cells frequently developed viral and/or bacterial pneumonia and enteritis. Three characteristic hematologic patterns occurred among the inoculated animals and correlated well with the probability of survival. Postmortem examination of the animals revealed lymphadenopathy and thymic atrophy. M-PMV was present in lymph nodes, blood, brain, spleen, thymus, kidneys, and bone marrow. The disease induced in some animals had characteristics suggestive of a slow-virus-induced autoimmune response.

Anemia↗

Biological basis for vertical ramus osteotomies--a study of bone healing and revascularization in adult rhesus monkeys.

Fifteen adult rhesus monkeys were used as experimental models to investigate revascularization and bone healing associated with pedicled and nonpedicled vertical ramus osteotomies and to elucidate the problem of vascular ischemia of the proximal segment and healing of the osteotomized bone. Microangiographic and histologic studies of vertical ramus osteotomies in which the proximal segment was not pedicled to soft tissue showed intraosseous necrosis, vascular ischemia, and delayed healing. Similar studies of pedicled vertical ramus osteotomies showed early osseous union, minimal osteonecrosis, and minimal vascular ischemia. The results indicate that continuous circulation to the proximal segment is necessary to retain osseous viability and to support the clinical practice of pedicling the proximal condylar segment to the articular capsule and lateral pterygoid muscle.

Animals↗

Neuropharmacological effects of methotrexate perfused through the cerebrospinal fluid system of the rhesus monkey.

Thirteen adult Rhesus monkeys were repeatedly perfused through the ventriculocisternal or ventriculolumbar spaces with Elliott's B solution containing various concentrations of methotrexate (MTX) and trace amounts of [3H]MTX and [carboxy-14C]inulin. The concentrations of MTX ranged from 4.8 to 0.15 mg/ml representing perfusion dosages of 551 mg/sq m to 16 mg/sq m. The average steady-state concentration out-concentration in (Co/Ci) value for MTX was 0.78 +/- 0.04 for the ventriculocisternal and 0.66 +/- 0.01 for the ventriculolumbar routes. MTX treatments did not significantly affect mean inulin steady-state Co/Ci values or CSF formation rate. With the exception of a monkey perfused with MTX at an inflow concentration of 4.8 mg/ml, body weight, food intake, and urine output, analyzed at weekly intervals, generally were not remarkably affected by MTX perfusions. In five monkeys perfused with MTX in concentrations of 4.8 to 0.6 mg/ml, gross neurological toxicity was observed, principally in the form of seizures and hypokinesia during perfusion series with occasional residual motor deficit. Significant cerebral damage was associated with the brains of two monkeys perfused with MTX at concentrations of 2.4 and 0.6 mg/ml and two monkeys perfused at concentrations of 1.2 and 0.3 mg/ml; there of the four animals displayed signs of gross neurotoxicity, and two animals developed permanent motor deficits. However, the extent to which neurotoxic signs could be attributed solely to MTX was difficult to judge because some changes in central nervous system morphology were associated with the mechanical aspects of the procedure. Overall behavioral performance as measured by a visual pattern discrimination reinforced by avoidance or escape from an electric shock was not significantly affected by repeated perfusions of MTX (0.6 mg/ml) in two monkeys not otherwise studied in detail.

Animals↗

Rapid categorization of natural images by rhesus monkeys.

Two rhesus macaques were tested on a categorization task in which they had to classify previously unseen photographs flashed for only 80 ms. One monkey was trained to respond to the presence of an animal, the second to the presence of food. Although the monkeys were not quite as accurate as humans tested on the same material, they nevertheless performed this very challenging visual task remarkably well. Furthermore, their reaction times were considerably shorter than even the fastest human subject. Such data, combined with the detailed knowledge of the monkey's visual system, provide a severe challenge to current theories of visual processing. They also argue that this form of rapid visual categorization is fundamentally similar in both monkeys and humans.

Animals↗

Effects of influenza, mumps, and western equine encephalitis viruses on fetal rhesus monkeys (Macaca mulatta).

Pregnant Rhesus monkeys were infected via instillation of influenza, mumps and western equine encephalomyelitis viruses respectively into the amniotic sacs at approximately 90 days gestation to determine if fetal infections would occur. Virus was recovered from fetal tissues after seven days in 100% of the exposed animals. Thus, the viruses are capable of causing fetal infection. Rhesus monkey fetuses were inoculated with influenza, mumps and WEE viruses by the direct intracerebral route at approximately 90 days gestation to determine possible teratogenicity of the viruses. influenza virus caused no malformations or measurable fetal effects. Mumps virus resulted in significant fetal mortality. WEE virus resulted in a 100% incidence of encephalitis and hydrocephalus. Thus, mumps and WEE viruses are teratogens in primates and are potential teratogens of man.

Animals↗

Comparison of Cardiovascular Parameters and/or Serum Chemistry and Hematology Profiles in Conscious and Anesthetized Rhesus Monkeys (Macaca mulatta).

The rhesus monkey is often used in pre-clinical research, and such studies frequently involve a variety of anesthetic conditions. Therefore, it is important to determine baseline physiologic blood chemistry and cardiovascular parameters in anesthetized animals to facilitate appropriate comparisons. The present study compares the cardiovascular parameters, hematology, serum chemistry, and blood gas levels of rhesus monkeys anesthetized with pentobarbital, isoflurane, ketamine, and propofol. Hematology, serum chemistry, and blood gas levels were unaffected by the four anesthetic regimens. However, because of its formulation, propofol is inappropriate for use in animals in which changes in tryglycerides will be evaluated. Compared to those in conscious, unrestrained monkeys, heart rates were higher in anesthetized animals, but the rates of anesthetized animals were similar regardless of anesthetic agent used. In contrast, mean arterial blood pressure was lower in animals anesthetized with pentobarbital, propofol, or isoflurane than in the conscious monkeys. However, mean arterial pressure of ketamine-anesthetized monkeys was similar to that of the conscious monkeys.

Journal Article↗

Testosterone metabolic clearance rate and production rate in the male infant rhesus monkey.

The male infant rhesus monkey (Macaca mulatta) undergoes a period of testicular activation similar to that seen in the human infant. Plasma testosterone (T) concentrations rise after birth, reaching levels of about 500 ng/dl at 1-3 mo of age and then fall to approximately 50 ng/dl at 60 mo. The plasma T metabolic clearance rates (MCRT) and production rates (PRT) were measured in two rhesus infants at 1 and 6 mo of age to determine the mechanism of the observed increase in plasma T. While there was little change in the MCRT between 1 and 6 mo, PRT was much higher at 1 mo than at 60 mo of age. These observations are consistent with the hypothesis that the increased plasma testosterone levels in infant rhesus monkeys reflect an increased production of testosterone rather than an altered metabolic disposition of the hormone.

Age Factors↗

Influence of continuous gonadotropin-releasing hormone (GnRH) agonist treatment on luteinizing hormone and testosterone secretion, the response to GnRH, and the testicular response to human chorionic gonadotropin in male rhesus monkeys.

Five adult male rhesus monkeys were continuously infused for 56 days with 25 micrograms/day of GnRH agonist (Wy-40972; Ag) using an implanted osmotic pump. Bioassayable serum levels of LH were elevated 8-fold on the second day of Ag treatment and then declined precipitously to below pretreatment levels by day 15. Serum levels of testosterone (T) changed similarly during Ag treatment, except that the fall in serum LH levels preceded the decline in serum levels of T by at least 2 days. Ag administration also eliminated the diurnal variation in serum LH and T. GnRH administration (50 micrograms) induced a 13- to 20-fold rise in serum LH and a 3- to 7-fold increase in serum T in control monkeys. After 4 weeks of Ag administration , none of the animals responded to GnRH. Both control and experimental monkeys had a rise in serum T in response to hCG after 7 weeks of Ag treatment. Basal levels of LH and T returned to normal by 12 days posttreatment, and the serum LH and T responses to GnRH were normal 19 days posttreatment. These results indicate that 1) continuous administration of Ag is an effective method of inducing antiferility effects in male rhesus monkeys; 2) pituitary desensitization is a major factor involved in Ag-induced gonadal dysfunction in this species; and 3) the method of administration may be the critical factor in determining the effectiveness of GnRH agonists.

Animals↗

[Normal antistreptolysin titres and demonstration of rheumatoid factors in rhesus monkeys (Macaca mulatta) (author's transl)].

Rhesus monkeys are often used as experimental animals. Many clinical and biochemical parameters are known but there are only few papers dealing with the normal values of antistreptolysin O (ASL). Informations about antistreptococcal antibodies are necessary in order to follow the course of immunization and infection experiments. When non-absorbed sera were used, the mean value of antistreptolysin O in clinically healthy rhesus monkeys (Macacus rhesus) amounted to 178 +/- 52 ASU. After absorption with dextran sulphate, the mean value was 90 +/- 20 ASU. Absorption with dextransulphate is a necessary prerequisite to exact determinations of antistreptolysin titres because it removes unspecific inhibitors of streptolysin O. In the sera of rhesus monkey more inhibitors were present than in human sera. On an average, in monkeys 55% of the material reacting with streptolysin O was an inhibitor, compared with about 40% in human sera. As a result of common infections with streptolysin O-producing streptococcal groups C and G antistreptolysin titres can frequently be seen to increase above the average normal value. Using non-absorbed and dextran sulphate absorbed sera, respectively 350 and 200 ASU must be regarded as the normal upper limits for serum antistreptolysin-titres.

Animals↗

Sequestration pattern of parasitized erythrocytes in cerebrum, mid-brain, and cerebellum of Plasmodium coatneyi-infected rhesus monkeys (Macaca mulatta).

Six rhesus monkeys (Macaca mulatta) infected with Plasmodium coatneyi were studied for parasitized red blood cell (PRBC) sequestration in microvessels of the brain. The degree of PRBC sequestration is different in the cerebral, mid-brain, and cerebellar microvessels, with sequestration occurring preferentially in the cerebellum. This pattern resembles that of PRBC sequestration in cerebral and cerebellar microvessels in human falciparum malaria. The morphologic appearance of sequestered cells under light and electron microscopy as well as the PRBC sequestration pattern bolsters the contention that the rhesus monkey infected with P. coatneyi is an appropriate primate model for the experimental study of human cerebral malaria.

Animals↗

Effects of feeding selenium deficient diets to rhesus monkeys (Macaca Mulatta).

Pregnant rhesus monkeys (Macaca mulatta) were fed either selenium (Se) deficient or Se supplemented diets with adequate vitamin E. Except for some cardiac irregularities in the first babies born to these females, no physiological disorders due to Se deficiency were seen in a subsequent offspring. Plasma and erythrocyte glutathione peroxidase activities and blood Se levels increased in the Se supplemented monkeys but decreased in the deficient ones. The data indicated that hair Se levels reflect long term exposure to this element. In a very preliminary experiment, evidence was obtained to indicate that dietary protein deficiency along with Se deficiency will generate cardiomyopathic lesions characteristic of Se deficiency. It is hypothesized that, in addition to Se deficiency, another dietary deficiency (or abnormality) is necessary to produce Se deficiency lesions in higher primates. Higher glutathione transferase (or non-Se glutathione peroxidase) activity in tissues of rhesus monkeys may account for this resistance.

Animal Nutritional Physiological Phenomena↗

On the mechanism of the positive feedback action of estradiol on luteinizing hormone secretion in the rhesus monkey.

In women and rhesus monkeys, both the negative and positive feedback actions of estradiol (E2) on gonadotropin secretion (inhibition followed by a surge) can be exerted directly at the level of the pituitary gland. We have tested the hypothesis that the positive feedback action of E2 represents but an "escape" from its negative feedback inhibition of gonadotropin secretion consequent to a desensitization of the gonadotropes occasioned by sustained exposure to elevated concentrations of the steroid. We have attempted to replicate such a desensitization by blocking the negative feedback action of E2 by the administration of a potent estrogen receptor antagonist devoid of any agonistic properties (ZM 182,780) to rhesus monkeys in the midfollicular phase of the menstrual cycle (n = 14). The estrogen antagonist, administered at a dose that in separate experiments completely blocked both the negative and the positive feedback effect of exogenous E2 on pituitary LH secretion, failed to produce a surge-like increase in serum LH concentrations. The present results do not support the hypothesis that the LH surge is the consequence of the removal of the negative feedback action of E2. Evidence is presented that ZM 182,780, in contrast to its inhibition of E2-induced LH surges, cannot block the inhibition of hypothalamic GnRH pulse generator activity by E2.

Animals↗

The effects of rigid fixation on craniofacial growth of rhesus monkeys.

A male infant rhesus monkey model was used to examine the growth effect on the craniofacial skeleton caused by osteotomy and three types of fixation: interfragmentary wiring, microplate and screw fixation, and "extensive" microplate and screw fixation. The animals (n = 12) were allowed to mature until cranial growth was at least 95 percent complete. Direct craniometric measurements were obtained and analyzed for differences in the three treated groups. A group of unoperated male animal skulls also was analyzed as controls (n = 5). A subtle visible and measurable restriction of growth in the operated area occurred in all treatment groups. Significant differences (p < 0.05) were found in only 4 of the 39 craniometric chords measured. Interfragmentary wiring showed fewer growth-restrictive effects than standard use of microfixation plates. Extensive use of rigid fixation devices caused the greatest degree of growth disturbance. Osteotomy and fixation in the infant rhesus monkey affect craniofacial growth, with the degree of growth restriction increasing with the amount of fixation hardware.

Animals↗

Consequences of social conflict on plasma testosterone levels in rhesus monkeys.

Four adult male rhesus monkeys formed a new social group with 13 adult females. The male who became dominant [alpha] showed a progressive increase in plasma testosterone. The male who became subordinate to the other three males showed an 80% fall in testosterone from baseline levels. After 7 weeks, this group was introduced to a well-established breeding group, and all four males became subordinate to all members of the breeding group. All four males evidenced a fall in testosterone during the first week after introduction, and within 6 weeks their levels were approximately--80% of pre-introduction values. The alpha male of the breeding group showed a large increase in testosterone [238%] 24 hr after he successfully defended his group and became the dominant animal of the larger, newly-formed group. Thus, plasma testosterone levels appear to be significantly influenced by the outcome of conflict attendant to alterations in status of rhesus monkeys living in social groups.

Aggression↗

Effect of a gonadotropin-releasing hormone agonist on luteinizing hormone and testosterone secretion and testicular histology in male rhesus monkeys.

Three adult male rhesus monkeys were treated for 20 weeks with a gonadotropin-releasing hormone (GnRH) agonist (Ag; Wy-40972; Wyeth Laboratories, Philadelphia, PA) using osmotic minipumps. Ag administration resulted in a transient increase and then a precipitous decrease in the concentration of luteinizing hormone (LH) and testosterone (T). After 5 weeks, serum levels of LH were undetectable (less than 0.2 microgram/ml), while serum T was always detectable, but continued to fall throughout the period of Ag administration. The serum LH and T response to 50 micrograms of GnRH was abolished by 4 weeks of Ag treatment, and this effect persisted through the treatment period. Testicular histology at 20 weeks of Ag treatment exhibited diffuse atrophy of seminiferous tubules, suppressed germinal cell division, and the absence of spermatids or spermatozoa. There was no evidence of testicular necrosis or calcification of the seminiferous tubules. Following the termination of Ag infusion, serum LH and T concentrations rebounded to levels that exceeded pretreatment values for a 5-week period before falling back to baseline levels. A complete restoration of spermatogenesis and testicular volume occurred by 12 weeks after treatment. These data suggest that continuous Ag administration is an effective method of reversibly disrupting spermatogenesis in the male rhesus monkey.

Animals↗

Effectiveness of prostaglandin f 2 alpha in restoration of HMG-HCG induced ovulation in indomethacin-treated rhesus monkeys.

Six mature female rhesus monkeys were treated with HMG-HCG in control cycles at doses adjusted to induce ovulation while avoiding superovulation. Occurrence of ovulation was determined by observation of fresh ovulation points at laparotomy 48 to 120 hours following HCG. In subsequent cycles animals were treated with indomethacin (treatment days 4 through 10) together with the established dose of HMG-HCG. In 8 cycles indomethacin 5 mg/kg was given i.m. once daily; in 9 cycles 10 mg/kg i.m. was administered in 2 divided doses. Following this, PGF2alpha (3 mg t.i.d. s.c.) was administered for 3 days together with indomethacin 10 mg/kg and HMG-HCG, beginning on the day prior to HCG. Determinations of progesterone were performed by RIA on treatment days 4, 7, 10, and 11. Eleven of the 13 control cycles were ovulatory. With indomethacin 5 mg/kg/day, 5 of 8 cycles were ovulatory but ovulation was delayed in 2 instances. Of 9 cycles using indomethacin 10 mg/kg/day only 1 was ovulatory. When PGF2alpha was administered in susequent cycles along with indomethacin (10 mg/kg) and HMG-HCG, ovulation occurred in 13 of 19 cycles. These data suggest that local ovarian PGF2alpha may be essential in the mechanics of follicle rupture in gonadotropin-treated rhesus monkeys.

Animals↗

Rhesus monkey (Macaca mulatta) model of Helicobacter pylori: noninvasive detection and derivation of specific-pathogen-free monkeys.

BACKGROUND AND PURPOSE: Development of the rhesus monkey model of Helicobacter pylori has been hampered by problems with serodetection and by the difficulty of identifying specific-pathogen (Helicobacter)-free animals. Our purpose was to determine whether detection could be improved and to determine if pathogen-free monkeys could be derived by nursery rearing. METHODS: An enzyme-linked immunoabsorbent assay (ELISA) and a [14C]urea breath test were compared to endoscopy to determine H. pylori infection status in rhesus macaques; 18 animals were hand raised in the nursery to determine whether pathogen-free animals could be selected. RESULTS: Helicobacter pylori infection was common in colony-raised young rhesus monkeys and was nearly universal by adulthood. Serodetection, using antigen from rhesus-derived H. pylori strains, was 95% sensitive and 94% specific. The [14C]urea breath test was 96% sensitive and 88% specific for detection of chronic Helicobacter infection in rhesus monkeys. Segregation of newborn animals within the first 24 h of life was a reliable method to obtain pathogen-free rhesus monkeys. CONCLUSION: Isolation of specific-pathogen-free animals, together with better detection methods, may improve the value of the rhesus monkey model for the study of H. pylori pathogenesis, immune response, and vaccine development.

Animals↗