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PubMed1976

A nonhuman primate vascular shunt model for thrombus generation.

A nonhuman primate model for thrombus generation was developed. Three different types of test devices constructed of polystyrene or polyethylene-Silastic were exposed to flowing blood in arterioarterial or arteriovenous vascular shunts in rhesus monkeys. The test device design included a simple tube, a vortical flow device, and a turbulent flow device. The amount of thrombus deposited within each individual test device after a 15-minute exposure to blood flowing through the shunt was determined gravimetrically. These studies indicate that a test device designed to include an area of vortical flow generated the greatest amount of thrombus. Test devices fabricated from polystyrene consistently generated larger thrombus deposits than did similar test devices fabricated from polyethylene-Silastic. Arteriovenous shunts proved superior to arterioarterial shunts in that flow was predictable in the former and unpredictable in the latter; venovenous shunts thrombosed quickly. Hematologic studies indicated a progressive fall in platelet count during the 4-hour test interval in all animals, whereas in only a few animals were there a shortening of partial thromboplastin time values, a fall in fibrinogen levels, and the appearance of fibrin degradation products. An optimal model for thrombus generation appears to include vortical flow test devices fabricated of polystyrene exposed to flowing blood in an arteriovenous shunt.

Animals↗

PubMed1976

Effects of antithrombotic agents evaluated in a nonhuman primate vascular shunt model.

The effects of aspirin, cyproheptadine, dextran, dipyridamole, and sulfinpyrazone on thrombus deposition were determined. These antithrombotic agents were evaluated in a nonhuman primate model for thrombus generation that employed test devices exposed to blood in an arteriovenous shunt. Thrombus deposition on test devices was quantitated gravimetrically. Of the antithrombotic agents tested, cyproheptadine was found to be the most effective, and aspirin, dextran, and dipyridamole were each somewhat less effective. Sulfinpyrazone had only a slight antithrombotic effect. Ultrastructual studies of thrombus deposited in test devices showed that the various antithrombotic agents tested did not prevent completely the formation of fibrin, aggregation of platelets, or adhesion and spreading of platelets and leukocytes. This model for thrombus generation is felt to be a more efficient means for evaluating antithrombotic agents than previously described nonhuman primate models.

Animals↗

PubMed1976

Contractile function and 45Ca movements in vascular smooth muscle of nonhuman primates: effects of aminoglycoside antibiotics.

1. The effects of 7mM neomycin, 10 mM kanamycin and 5 mM gentamicin on vascular smooth muscle contractile responses and 45Ca movements were examined in arterial preparations isolated from nonhuman primates (squirrel monkeys, capuchin monkeys and baboons). 2. Present findings demonstrate that these antibiotics inhibit contractile responses and alter 45Ca movements in monkey blood vessels, and suggest that the manner in which these agents affect vascular smooth muscle from nonhuman primates does not differ qualitatively from their effects in canine and rabbit vascular preparations.

Aminoglycosides↗

PubMed1977

Characterization of plasma low density lipoproteins on nonhuman primates fed dietary cholesterol.

LDL from animals of three nonhuman primate species, Macaca mulatta, Macaca fascicularis, and Cercopithecus aethiops, were studied. A standard preparation of 125I-LDL was added to isolated lipoprotein mixtures just prior to separation of plasma lipoproteins by agarose gel chromatography. A relative size index, rI, was determined by dividing the elution volume of the iodinated LDL by the elution volume of the sample LDL, both volumes being determined simultaneously during chromatographic elution. Comparison of rI with molecular weights measured by flotation equilibrium analysis in the analytical ultracentrifuge showed a linear relationship across a molecular weight range of 2.5-8.0 X 10(6), r = 0.985. A regression equation describing this relationship was used to calculate molecular weights of LDL from a group of M. fascicularis that were fed cholesterol-containing diets. In these animals, plasma cholesterol concentration ranged from 100 to over 700 mg/dl and was highly correlated with LDL molecular weight and with the micromolar concentration of the LDL. Using multiple regression analyses, the two variables of plasma LDL could be shown to account for 94% of the variation in plasma cholesterol concentration in the M. fascicularis of this study. Micromolar concentration and molecular weight of LDL were not correlated with each other, suggesting that in M. fascicularis at least two independent types of controls are operative in the response of plasma LDL to dietary cholesterol. The increase in LDL molecular weight was associated with a large increase in cholesteryl ester content and concomitant smaller increases in protein, phospholipid, and free cholesterol. As molecular weight increased, these components appeared to be added to the LDL particles together as discrete increments of fixed composition. The data are consistent with a spherical model of LDL structure with a core of cholesteryl ester and triglyceride and a 21.3 A-thick coat of phospholipid, free cholesterol, and protein.

Animals↗

PubMed1976

Induction of liver tumors by aflatoxin B1 in the tree shrew (Tupaia glis), a nonhuman primate.

The epidemiological studies suggest that aflatoxins, the toxic metabolites of the ubiquitous mold Aspergillus flavus, may play a significant role in the evolution of hepatocellular carcinoma in man in certain geographic areas of the world. To ascertain their carcinogenicity in nonhuman primates, we have administered highly purified aflatoxin B1, intermittently in the diet at 2 ppm, to 10 female and 8 male tree shrews. The tree shrew (Tupaia glis) is a nonhuman primate occurring throughout Southeast Asia which can be reared easily in captivity. Of 12 animals that survived, 6 of 6 female (100%) and 3 of 6 male (50%) tree shrews developed hepatocellular carcinomas between 74 and 172 weeks after the beginning of the experiment. None of the 8 control animals developed liver cancers. The estimated total amount of aflatoxin B1 consumed by these animals ranged from 24 to 66 mg. The development of liver tumors did not follow a specific pattern; considerable variation in hepatocellular responses to aflatoxin B1 was noted in these animals. In 2 tree shrews, the liver tumors were associated with severe post necrotic scarring; in the other 7 tumor-bearing livers, only mild to moderate portal fibrosis was encountered. This individual variation in hepatocellular response and in the amount of aflatoxin B1 required to induce hepatocellular carcinomas is attributed to inherent differences in the susceptibility within a given species of outbred animals and suggests extreme caution in proposing the "permissible" or "safe" levels of contamination of carcinogens in the food-stuffs.

Aflatoxins↗

PubMed1975

Human melanoma and leukemia associated antigens difined by nonhuman primate antisera.

The rationale of our approach to the detection and characterization of human leukemia and melanoma associated membrane antigens is to take advantage of the unique immunological recognition perspective of simians to huamn antigens. There are enough antigenic similarities between man and nonhuman primates to blunt the immune response of apes and monkeys to huamn species-specific antigens. Their response to allogeneic normal human antigens such as HL-A can now be managed by in vitro absorption procedures. High titered antibodies specific for tumor associated membrane antigens have not been well documented in serological studies with patients' sera. Immunization of nonhuman primates utilizes a fully immunocompetent recipient who has no tumor and is not on chemotherapy. The immunization can utilize adjuvants and other regimens that morally and ethically cannot be easily used for human allogeneic immunization. The simian antisera that are shown to be specific for human tumor membrane antigens can then be utilized for studies on the isolation and characterization of the antigens. Similar studies with HL-A antigens indicated that the solubilized partially purified antigens can then be used to elicit high titered antibodies in other simians. These latter antisera can then be used for more sensitive assays and studies on the association of the antigen(s) with the cell membrane. Although the work summarized here covers leukemia and melamona antigens, it is felt the approach will serve as a model for the detection by simian antisera of tumor-specific membrane antigens of cancer cells from patients with various types of solid tumors.

Animals↗

PubMed1975

Cephalometric roentgenography for nonhuman primates utilizing a surgically implanted head positioner.

Cephalometric roentgenography in nonhuman primates requires more precise head positioning than that afforded by commonly used ear rod techniques. A standard cephalometric headholder was therefore modified and a technique was developed to implant an attachment that permit precise positioning of the head in all three planes of spce. This method has been used in 36 animals, and at 35 months postsurgery the implants have remained stable and tissue compatiblity is generally excellent. Roentgenograms obtained with this technique offer a high degree of accuracy in documenting growth changes and response to orthodontic treatment.

Animals↗

PubMed1979

Percentage ash content of nonhuman primate long limb bones.

Trotter and Hixon ('76) and Vose and Roach ('72) presented conflicting data about percentage ash content of the long limb bones of M. mulatta and M. nemestrina. The suggestion of Trotter and Hixon ('76) that this discrepancy was due to methods of preparing the bone prior to ashing, rather than to species differences, was tested using data collected by Gong ('72) on the volumetric composition of nonhuman primate bone. Masses of the various chemical fractions of bone reported by Gong ('72) were used to compute ash content as a percentage of total dry weight and ash content as a percentage of fat-free dry weight. Good agreement was found between ash content as a percentage of total dry weight and the data of Vose and Roach ('72); good agreement was also found between ash content as a percentage of fat-free dry weight and the data of Trotter and Hixon ('76). This suggests that the data of Vose and Roach ('72) conflict with those of Trotter and Hixon ('76) because Vose and Roach ('72) failed to defat the bones prior to ashing. No actual species differences exist in the ash content of bones of M. mulatta and M. nemestrina. The data of Trotter and Hixon ('76) are most likely a more adequate reflection of both the magnitude and the regional similarity of ash content in nonhuman primate bone.

Animals↗

PubMed1975

Nonhuman primate restraint device for ocular drug studies.

A restraining device for nonhuman primates was designed which effectively prevented the animal from touching the eyes and thereby transferring a topically applied drug from 1 eye to the other. This permitted use of 1 eye of the same animal as a reliable control for observation of pharmacologic effects. The design permitted self-feeding by the animal. It did not produce chafing or pressure sores and resulted in no psychologic depression. The device has been used successfully for a 5-mo period.

Animals↗

PubMed1979

Rearing of conventional and gnotobiotic nonhuman primates (Pan troglodytes, Papio cynocephalus, Saguinus nigricollis).

Rearing techniques for conventional and gnotobiotic nonhuman primates are described. Up to four months of age there was no significant difference in weight gain between conventionally and gnotobiotically reared chimpanzees or baboons. After four months, gnotobiotic chimpanzees exceeded their conventional counterparts in weight gain, whereas conventional baboons showed higher weight gain than gnotobiotic baboons. Gnotobiotic chimpanzees and baboons had significantly lower absolute numbers of neutrophils than their conventional counterparts, but the absolute numbers of lymphocytes were not different. The gnotobiotic rearing of marmosets is also reported.

Animal Feed↗

PubMed1979

A rapid procedure for shortening canine teeth of nonhuman primates.

A modified pulp cap procedure was utilized to shorten canine teeth of nonhuman primates. A temporary cap was made by cutting the tooth with a diamond-faced cutting disc, making a conical cavity in the tooth with a carbide dental burr, and filling the cavity with a rapid-hardening filler material. A permanent pulp cap was made by repeating the above technique, making three anchor holes, connecting the holes with a furrow, and capping with quick-setting dental restorative material or amalgam. These procedures provided a simple, rapid and uncomplicated alternative to canine tooth extraction.

Animals↗

PubMed1977

Computer program for maintenance of individual animal records in a nonhuman primate colony.

A computer program was developed to maintain animal records for a nonhuman primate colony used in research. The program was designed for use with an existing laboratory notebook system. The computer program identifies each notebook entry containing information about each animal and keeps other information, including animal name, sex, species, projects to which the animal is assigned, location of the animal, dates and body weights. The program is interactive and easy to use. Information stored in the system is readily accessible to all investigators using the animals. In 17 months of use, 1382 master file entries were developed for 113 monkeys.

Animals↗

PubMed1977

Carbohydrate composition of serum low and high density lipoproteins of nonhuman primate species.

1. Carbohydrate composition of serum low and high density lipoproteins obtained from 5 nonhuman primate species (chimpanzee, patas, baboon, rhesus, and spider) and humans was studied. 2. Individual lipoproteins were isolated from pooled sera of each species by ultracentrifugal flotation between the densities 1.019-1.063 for LDL-2; 1.063-1.12 for HDL-2; and 1.12-1.21 for HDL-3. After delipidation, sialic acid, fucose, glucosamine, mannose, galactose, and glucose were determined on apo LDL-2, apo HDL-2, and apo HDL-3. 3. Glucosamine, galactose, and mannose constituted a major component of the sugars in apo LDL-2, with similar relative proportions in all species. Sialic acid, fucose, and glucose formed a minor component, the proportions of which varied greatly among the species. 4. Unlike apo LDL-2, sialic acid, fucose, and glucosamine constituted the bulk of the sugars in apo HDL-2 and apo HDL-3. Mannose, galactose, and glucose were minor components, with galactose predominating. 5. Qualitative differences were observed in electrophoretic mobilities of apo HDL-2 and apo HDL-3 on polyacrylamide gel. One faster moving band was unique to chimpanzee. 6. Intraspecies differences in the content of sialic acid and fucose of apolipoproteins may be related to lipoprotein metabolism and species susceptibility (or resistance) to either spontaneous or diet-induced atherosclerosis.

Animals↗

PubMed1976

A simple restraining device for use with neonatal and small nonhuman primates.

A simple and inexpensive restraining device was designed for use with neonatal and small nonhuman primates weighing less than 2 kg. With this device a technician working alone can collect blood samples, fecal or vaginal smears, nasal or oral swabs, or perform a variety of routine procedures including physical examination and administration of medication.

Animals↗

PubMed1977

Nonhuman primates: laboratory animals of choice for neurophysiologic studies of sleep.

A systematic study was made of several nonhuman primates to learn more about their relative usefulness for studies of sleep. Species studied included the Guinea baboon (Papio papio), Kenya or yellow baboon (P cynocephalus), olive baboon (P anubis), sacred baboon (P hamadryas), vervet monkey (Cercopithecus aethiops), rhesus monkey (Macaca mulatta), bonnet monkey (M radiata), crab-eating monkey (M fascicularis), patas monkey (Erythrocebus patas), chimpanzee (Pan troglodytes), mongoose lemur (Lemur mongoz), black lemur (Lemur macaco fulvus), and bushbaby (Galago senegalensis). Comparisons were made of electroencephalographic activity, states of vigilance, and responses to sleep-waking drugs. The results showed that there were major similarities among the genera studied as well as individual intrageneric and intraspecies differences. It was concluded that the chimpanzee, olive baboon, and rhesus monkey were the best species for comparative studies, and that the rhesus monkey was the best single model because of its well defined sleep organization and ease of handling and housing.

5-Hydroxytryptophan↗

PubMed1976

A model for therapeutic interventins on established coronary atherosclerosis in a nonhuman primate.

The observations so far conducted in cynomologus monkeys on semipurified diets containing butter and cholesterol suggest that this nonhuman primate is an excellent model for studying the therapy of established coronary atherosclerosis. (1) This species is available at a reasonable cost and can be kept in captivity in good health for prolonged periods of time. (2) It readily accepts semipurified diets with a percentage composition similar to that of human diets in the U.S. (3) Ingestion of these diets leads quite rapidly (around 6 months) to moderate coronary atherosclerosis. More prolonged feeding leads to lesions which are histologically very similar to those in man. (4) The distribution of lesions in the main coronary arteries is similar to that in man. (5) Methods to quantify the coronary lesions are available. (6) The diets can be so modified that cholesterol levels closely resemble those in hypercholesterolemic man. (7) The monkeys are amenable to several therapeutic regimens which show promise of arresting the progress or inducing the regression of the coronary lesions.

Animals↗

PubMed1976

Carcinogen-induced cutaneous neoplasms in nonhuman primates.

Dimethylbenzanthracene (DMBA) combined with UV light, dodecylbenzene (DDB), or both was oncogenic when applied to the skin of nonhuman primates. Ten years after the cutaneous application of DMBA and a cocarcinogen, 2 groups of rhesus monkeys (Macaca mulatta) displayed dermal melanosis, papillomas, basal cell tumors, and mesodermal sarcomas (accompanied in one case by hepatic metastasis). One group had been painted for 15 months; the other, for 6 1/2 years. Eight years after the initiation of a 4-year regimen of biweekly applications of DMBA plus a cocarcinogen, papillomas, basal cell tumors, and basosquamous cell epidermal tumors with satellite lipomas were observed in galagos (Galago crossicaudatus). The same carcinogen applied to the skin of pottos (Perodicticus potto) caused death in 6 of the 7 animals within 9 weeks. Neoplasms occurred in 17 of the 19 primates that lived longer than 9 weeks after the cutaneous application of DMBA combined with either UV light or DDB.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1977

The capacity for computed tomography diagnosis of cerebral infarction. An experimental study in the nonhuman primate.

The characteristic serial CT scan appearance of cerebral infarction created by embolization of the middle cerebral artery in the nonhuman primate (10 baboons) is defined. The earliest CT changes are noted by 12 to 24 hours and include generalized ventricular enlargement and a focal region of decreased absorption in the opercula-basal ganglia region. The area of diminished brain absorption is better circumscribed and of lower attenuation coefficient with increasing chronicity. Distinct hydrocephalus, unilateral exophthalmos and ventricular displacement occurred with increased intracranial pressure. Little additional diagnostic information was obtained via intravenous enhancement and care should be taken as mild enhancement may obscure an area of abnormality.

Animals↗