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PubMed1989

In vivo formation of metabolites of prostaglandins I2 and I3 in the marmoset monkey (Callithrix jacchus) following dietary supplementation with tuna fish oil.

Recent studies have shown that ingestion of eicosapentaenoic acid (EPA) in man results in the formation of 'trienoic' prostanoids which amy partly explain the potent antithrombotic/antiatherogenic properties of long-chain polyunsaturated n-3 fatty acids (PUFAs). However, endogenous formation of cyclooxygenase metabolites of EPA has not been demonstrated in an animal model, and in vitro studies indicate a clear species difference in the conversion of EPA to PGI3. Thus, in the present study, the in vivo formation of PGI3 following long-term dietary tuna fish oil supplementation was investigated in a small non-human primate - the marmoset monkey (Callithrix jacchus). The excretion of major urinary metabolites 2,3-dinor-6-keto-PGF1 alpha (PGI2-M) and delta 17-2,3-dinor-6-keto-PGF1 alpha (PGI3-M) was estimated as an index of total body synthesis of PGI2 and PGI3, respectively. Following extraction, dinor prostanoid metabolites were separated by capillary gas chromatography and identified by negative ion chemical ionization mass spectrometry. Supplementation of the standard (reference) diet with either sheep fat or sunflower seed oil did not alter the body production of PGI2-M. However, following the tuna fish oil-enriched diet, there occurred not only an increase in urinary PGI2-M (reference 70.7 +/- 9.0; tuna fish oil 115.5 +/- 12.1 ng/g creatinine, P less than 0.05), but also a considerable formation of PGI3-M (62.9 +/- 5.3 ng/g creatinine), which was not seen in any other dietary group; in addition, the urinary level of immmunoreactive 2,3-dinor-thromboxane B2/3 was reduced after ingestion of tuna fish oil. These urinary changes were accompanied by a rise in plasma phospholipid-bound EPA and docosahexaenoic acid (DHA). In addition, tuna fish oil supplementation resulted in a significant reduction in plasma cholesterol (53%) and triacylglycerols (44%). The present study provides for the first time experimental evidence for the in vivo formation of PGI3 in an animal model and also confirms the earlier observations in man following dietary fish oil supplementation.

Animals↗
PubMed1988

Persistence of the pars externa system of the anterior olfactory nucleus in a microsmatic primate, Callithrix jacchus.

The pars externa (PE) system of the anterior olfactory nucleus (AON) in a primate, Callithrix jacchus, was defined by its architecture and by its connection patterns with the main olfactory bulb (MOB) as revealed by tracing techniques. Focal, unilateral injections of wheat germ agglutinin-conjugated horseradish peroxidase into the MOB yielded ipsilaterally labelled afferent neurons in all subdivisions of the AON, with the exception of a clearly circumscribed area in the ventrolateral retrobulbar field of the basocaudal frontal lobe; in the contralateral hemisphere, this same area contained intensely stained neurons forming a horizontal flat plate of small neurons. This unique commissural connection pattern parallels the organization of the PE to MOB connection in sub-primates (Schoenfeld and Macrides, 1984, J. Comp. Neurol., 227: 121-135). Thus, despite earlier controversy (Crosby and Humphrey, 1939, J. Comp. Neurol., 71: 121-213), there appears to be a PE system in a microsmatic primate whose organization is quite similar to that in sub-primates.

Animals↗
PubMed1987

Fetal brain development in response to iodine deficiency in a primate model (Callithrix jacchus jacchus).

The common cotton-eared marmoset (Callithrix jacchus jacchus) has been used for the first time as a primate model to study the effects of dietary iodine deficiency on fetal brain development. Paired male and female marmosets were fed a low-iodine diet of maize, peas, meat meal, Torula yeast, maize oil and added vitamins, minerals and amino acids for 6 months before mating. Offspring from first and second pregnancies were compared with offspring from control marmosets fed the same diet but supplemented with iodine. Severe iodine deficiency in the fetus at birth was evident by reduced plasma thyroxine levels, increased plasma thyroid stimulating hormone levels, increased thyroid weight and reduced thyroid iodine content. Thyroid histology revealed hyperplasia, hypertrophy and absence of colloid material in the follicles. Iodine deficiency caused a reduction in the weight of the fetal brain and in particular the cerebellum. Brain cell number was reduced in the cerebellum and brainstem but cell size was reduced in the cerebral hemispheres. Histology of the brain revealed morphological changes in the cerebellum and cerebral hemispheres. In the-cerebellum there was: an increase in the thickness of the external germinal layer indicative of impaired cell acquisition; a decrease in total area; a decrease in molecular layer area; and an increase in Purkinje cell (Pc) linear density due to a reduction in the length of the Pc line. The decrease in molecular layer area and increase in Pc linear density imply diminished ascending and lateral extension of Pc dendrites. Changes in the cerebral hemispheres consisted of an increase in the density of neuronal cell bodies in the granular band and a decrease in synaptic counts in the layer between the pia mater and supragranular band of the visual cortex. Offspring from second pregnancies compared to those from first pregnancies were more severely affected and associated with lower plasma levels of maternal and fetal thyroxine. These findings indicate the importance of maternal and fetal thyroid function in relation to fetal brain development in the primate.

Animals↗
PubMed1992

Sister-chromatid exchange rates in XX and XY cells of ten chimeric Callithrix jacchus individuals.

In order to ascertain whether or not sister-chromatid exchange (SCE) differs in relation to sex, SCE rates in XX and XY cells from 10 specimens of marmoset (Callithrix jacchus) were examined. The choice of this primate is particularly suitable for three reasons: most individuals have a chimeric constitution, the X chromosome is quite large and the Y chromosome is particularly small. Therefore, the influence of possible differences in their exposure to the external environment can be eliminated. The results obtained did not reveal any significant difference between SCE rates in male and female cells in any of the examined individuals.

Animals↗
PubMed1990

Evaluation of the toxicity of indomethacin in a 4-week study, by oral route, in the marmoset (Callithrix jacchus).

A subacute toxicity study of Indomethacin administered by oral route, was carried out in the marmoset (Callithrix jacchus). Groups of three males and three females received Indomethacin directly into the stomach by means of a catheter for a period of 4 weeks at the dose levels of 0, 2, 6, and 12 mg/kg body wt/day and then were euthanized for pathological evaluation. All marmosets given 12 mg/kg/day and one marmoset given 6 mg/kg/day died during the dosing period (within 20 days). At 12 mg/kg/day, Indomethacin induced severe gastrointestinal toxicity (hemorrhage, ulcers, and necrosis with peritonitis), while at the dosages of 6 and 2 mg/kg/day some moderate to slight dose-related functional and morphological renal alterations (increase of serum urea, reduction of serum albumin, increase of serum potassium and/or chloride, and subacute inflammation) were observed. The fact that in many respects these alterations are similar to those observed in man is a further demonstration of the validity of the marmoset as an experimental model.

Administration, Oral↗
PubMed1988

Chronic toxicity of 3,4,3',4'-tetrachlorobiphenyl in the marmoset monkey (Callithrix jacchus).

Cotton top marmoset monkeys (Callithrix jacchus) were orally dosed with 3, 1, 0.1 or 0 mg 3,4,3',4'-tetrachlorobiphenyl (TCB)/kg body weight twice per week for 18-23 weeks. Severe toxicity occurred in the highest dose group. Clinical signs of toxicity were a rapid decrease in body weight, alopecia, abnormal nail growth, nodular enlargement of the nipple area and scaly skin. Haematological analysis of peripheral blood revealed mild leukocytosis and anemia. Biochemical alterations observed were elevated triglyceride levels and cholesterol levels. Histopathology revealed dose dependent changes in a variety of tissues. Squamous metaplasia was found in skin and adnexa as well as in salivary glands. In the stomach, parietal cells were decreased and mucus producing cells were increased. The duodenal mucosa was hyperplastic. Ovaries showed an absence of corpora lutea. In the thyroid follicular cell hyperplasia and hypertrophy were noted. Toxicity was less severe in marmoset monkeys dosed with 1 mg TCB/kg, while minor toxic effects were observed in the animals dosed with 0.1 mg TCB/kg. The marmoset monkey appears to be less sensitive to the toxic action of TCB than the rhesus monkey. The pattern of histological and biochemical changes induced by TCB in marmoset monkeys is comparable to that described in humans and in other primate species exposed to PCBs. The marmoset monkey model may be valuable for investigations on human-related toxicity of PCBs.

Animals↗
PubMed1991

The effect of dietary change on in vitro erythrocyte haemolysis, skin lesions and alopecia in common marmosets (Callithrix jacchus).

1. The effect of dietary change on common marmosets (Callithrix jacchus) exhibiting high in vitro erythrocyte haemolysis, skin lesions and alopecia was investigated. 2. The experimental diet was low in lipid, high in vitamin E and was devoid of n-3 long chain polyunsaturated fatty acids. 3. There were significant increases in the concentrations of plasma alpha-tocopherol (vitamin E) (P less than 0.05), all-trans retinol (vitamin A) (P less than 0.001) and total lipid (P less than 0.025), and a reduction in fibrinogen (P less than 0.02) concentration and neutrophil count (P less than 0.02). 4. Moreover, the mean in vitro erythrocyte haemolysis declined from an initial value of 64% to less than 2%, and there was a regression of skin lesions and alopecia with complete fur regrowth. 5. The amelioration of the conditions appear to be due to high circulating vitamin E which provided protection against oxidative stress, and the correction of membrane n-6:n-3 balance.

Alopecia↗
PubMed1992

Differences in fatty acid composition of various tissues of the marmoset monkey (Callithrix jacchus) after different lipid supplemented diets.

1. The fatty acid composition of different muscles, organs and blood components of the marmoset monkey were examined after long-term feeding of several well defined lipid supplemented diets. 2. Similarities between the fatty acid composition of cardiac and skeletal muscles which persisted after all diets suggest that biopsy of skeletal muscle may have an important diagnostic value in this and other primate species. 3. The relationship between the dietary intake of individual fatty acids and their proportions in different tissues is both complex and variable. 4. However, the lipid metabolism of Callithrix jacchus recommends this small non-human primate as a most suitable species for the study of lipid nutrition.

Analysis of Variance↗
PubMed1991

Distribution and morphology of substance P-immunoreactive structures in the olfactory bulb and olfactory peduncle of the common marmoset (Callithrix jacchus), a primate species.

The present study describes the morphology and distribution of substance P-immunoreactive (SP-ir) elements in the olfactory bulb (OB) and olfactory peduncle (OP) of the common marmoset (Callithrix jacchus), a primate species. SP-ir neurons are very abundant in the OB and belong to two types. External tufted cells are present in the glomerular layer (GL), whereas granule cells are found in the deeper layers, especially in the granule cell layer (GRL), but also scattered in the OP. SP-ir fibers, putatively of central origin, were identified in the OP. They ascend into the bulbar layers. The SP-chemoarchitecture of the marmoset OB and OP does not differ more from rat, guinea pig and cat, than the SP-chemoarchitecture of these species varies among one another.

Animals↗
PubMed1985

Plasmodium brasilianum in the common marmoset Callithrix jacchus.

Chronic quartan malarial infection has been established in the common marmoset (Callithrix jacchus). Plasmodium brasilianum from a douroucouli monkey (Aotus trivirgatus) was used to infect splenectomized twin animals, passed to an intact animal, and then to 4 other intact adults, 2 pairs of twins. In 2 of the 4 latter animals there was continuing patency with parasitaemias of less than or equal to 0.5% parasitized erythrocytes for 30 weeks. The other 2 had lower initial levels of parasitaemia; in 1 of these parasitaemias remained low or subpatent. All marmosets developed lymphocytosis. One animal became ill 30 weeks after infection with anaemia, weight loss and mild proteinurea, the other 3 remained well. Histological examination showed minor changes in the kidneys; spleens of infected animals showed marked follicular hyperplasia and phagocytosis of pigment. The livers showed sinusoidal hypercellularity and pigment deposition and in splenectomized animals, a marked lymphoid follicular hyperplasia in the portal tracts.

Animals↗
PubMed1988

Plasmodium vivax malaria in the common marmoset, Callithrix jacchus: adaptation and host response to infection.

Infection with Plasmodium vivax was established in splenectomized Callithrix jacchus marmosets by inoculation of parasitized blood from Aotus trivirgatus carrying the Vietnam Palo-Alto line of P. vivax. Subsequent blood passage through intact marmosets resulted in higher peak parasitaemias (about 1% of red cells infected) and the loss of stainable Schüffner's dots in infected cells. Primary infections with the adapted line were patent for 74 days or more, and induced both a substantial antibody response, as determined by indirect fluorescence, and some lymphocytosis, but no marked anaemia. Marmosets which had recovered from their primary infection (or in which it was drug-cured) suffered abbreviated patency with low-grade parasitaemia on re-infection.

Animals↗
PubMed1985

Metabolism and tissue distribution of tobacco-specific N-nitrosamines in the marmoset monkey (Callithrix jacchus).

Three male marmoset monkeys (Callithrix jacchus) were injected i.v. with the tobacco-specific carcinogen [2'-14C]N'-nitrosonornicotine (NNN) (20.3 mumol/kg body weight) or [carbonyl-14C]4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (18.8 or 420 mumol/kg body weight). They were sacrificed 4 h later. Tissue distribution was studied in two monkeys by whole-body autoradiography and by computer-assisted densitometric analysis of the autoradiograms. The autoradiograms showed a high level of radioactivity in the liver, nasal mucosa, kidneys, melanin of the eyes, hair-follicles of the skin and in the ceruminous ear glands of the monkeys. Total level of radioactivity was 5.7 times higher in the liver of the [carbonyl-14C]NNK-injected monkey than in that of [2'-14C]-NNN-injected monkey. Washing the sections with trichloroacetic acid and organic solvents selectively removed free metabolites leaving metabolites bound to cellular macromolecules. Level of bound metabolites was 1.5 times higher in the nasal mucosa than in the liver of the [2'-14C]NNN monkey. Levels of bound metabolites were similar in the liver of NNN- and NNK-treated monkeys. The results indicate that the liver and nasal mucosa of C. jacchus can activate NNN and NNK to alkylating species. Unbound metabolites present in the liver, lung, kidneys, eye, blood and urine were extracted and separated by h.p.l.c. Hydroxylation of the carbons alpha to the N-nitroso group of NNN were the major metabolic pathways. Unmetabolized NNN was the major radioactive component in the liver, lung, eye and blood. Reduction of the carbonyl of NNK yields 4-(methylnitrosamino)-1-(3-pyridyl)butan-1-ol (NNAl). NNAl was present in all tissues analyzed and was the major radioactive component in the eye and stomach lumen. It was also excreted in the urine. NNK and NNAl were metabolized by alpha-carbon hydroxylation. These results suggest that in C. jacchus, NNN, NNK and NNAl are activated to alkylating species by alpha-carbon hydroxylation. In the third monkey injected with NNK, DNA methylation was observed in the liver and nasal mucosa but not in the lung and kidneys. Pulmonary tissues of C. jacchus, unlike those of F344 rats, do not have the enzymic capacities to activate NNK to methylating species.

Animals↗
PubMed1987

Radionuclide angiographic study of the influence of dietary lipid supplements on cardiac function in the marmoset (Callithrix jacchus).

Radionuclide angiography was used to examine the influence of dietary fat on cardiac function in the common marmoset monkey (Callithrix jacchus jacchus) under barbiturate anaesthesia. Animals were fed for 6-8 months with a low fat (4.5%) reference diet or the same diet supplemented (12%) with sunflower seed oil or sheep fat. Although there was a tendency towards increased heart rate, left ventricular ejection fraction, peak ejection rate, and peak filling rate in both fat supplemented groups, significant increases in heart rate (+50%), peak ejection rate (+71%), and peak filling rate (+84%) were found with sheep fat supplementation, whereas only the vegetable oil supplement produced a significant improvement in left ventricular ejection fraction (+23%). There were no differences in resting blood pressure, and the main consequence of dietary fat supplementation was a major increase in apparent cardiac oxygen consumption (+58%) with the sheet fat diet, as determined by the pressure-rate index. Infusion of isoprenaline hydrochloride (0.2 microgram.kg-1.min-1) increased all indices of cardiac function towards common maxima. There were no differences in either the depth or duration of anaesthesia between dietary groups. It therefore is unlikely that this contributed to any of the observed dietary induced differences in cardiac function. It is suggested that dietary saturated animal fat increased cardiac work and oxygen consumption at rest to the extent that functional reserve to respond to stress was significantly diminished. Feeding a linoleic acid rich polyunsaturated vegetable oil supplement was, however, accompanied by evidence of some improvement in left ventricular ejection fraction.

Animals↗
PubMed1987

Successful infection of the common marmoset (Callithrix jacchus) with human varicella-zoster virus.

The common marmoset, Callithrix jacchus, can be infected with human varicella-zoster virus (VZV), both wild-type strain KMcC and attenuated vaccine strain Oka/Merck. Infection was accomplished with either whole-cell-associated or cell extract VZV by combined oral-nasal-conjunctival application and was characterized by substantial and persistent anti-VZV antibody responses. The infectivity of VZV for marmosets was destroyed by treatment of inocula with heat or UV light. Diluted inocula with as few as 40 PFU/ml were infectious for marmosets. The lungs were demonstrated to be a major site of viral replication; both the presence of viral antigens and signs of pneumonia were demonstrated in lung tissues. Four serial passages of VZV KMcC were carried out in C. jacchus by a process of in vitro isolation and culturing of VZV from infected lung tissue and reapplication of the cultured isolates to fresh animals. The isolated viruses were identified as VZV both serologically and by restriction endonuclease analyses. The C. jacchus infectivity model should prove useful for determining the efficacy of subunit and live recombinant VZV vaccines as well as for the study of zoster.

Animals↗
PubMed1990

Immunofluorescence-microscopic localization of collagen type IV and VI, laminin and nidogen in the livers of Callithrix jacchus during pre- and postnatal development.

The distribution of collagen type IV and VI, laminin and nidogen was investigated by immunofluorescence microscopy in the livers of marmosets (Callithrix jacchus) at various stages of development, i.e. on days 93, 111, 116 and 134 of gestation, 1 day postpartum and at the mature stage. Large amounts of collagen type IV could in all cases be demonstrated in the sinus wall and in all basal laminae outside the lobule. After the application of antibodies against collagen type VI the sinus wall showed a weak fluorescence reaction at the early stages and a strong binding towards the end of gestation which persisted up to the adult stage. In the periportal field it was mainly localized at the border between lobule and connective tissue. Laminin also increased gradually but could be demonstrated only until birth. In contrast, nidogen was present during the total prenatal and postnatal period. Therefore, collagen type IV and VI were not very suitable for the demonstration of an increase in matrix components under pathological conditions, because they occur already in large amounts in normal livers. However, the occurrence of laminin that was missing in the adult liver must be interpreted as pathological indication. The different occurrence of laminin and nidogen showed that these two substances were expressed and regulated independently of each other.

Aging↗
PubMed1989

Systems for collection of urine in the captive common marmoset, Callithrix jacchus.

Two systems are described for the collection of 24 h urine samples from the common marmoset (Callithrix jacchus). Using 84 adult animals, 1210 24-h samples were collected. Mean urinary excretion was 14.4 +/- 7.5 ml/24 h (n = 1210, mean +/- SD). No differences were observed between sexes (for 52 females, 24 h volume = 15.1 +/- 8.0 ml; for 32 males, 24 h volume = 12.5 +/- 6.0 ml). No significant differences were observed between pregnant and non-pregnant females with respect to 24 h urine volume, and bilateral gonadectomy did not influence subsequent urinary excretion in either sex. For 161 pairs of observations, the intake of drinking water (11.7 +/- 10.2 ml/24 h) and the volume of urine excreted (12.6 +/- 7.1 ml/24 h) showed a positive correlation (r = 0.406 d.f. 159, P less than 0.001: y = 0.558x + 4.247).

Animals↗
PubMed1989

Heinz bodies do not modify the membrane characteristics of common marmoset (Callithrix jacchus) erythrocytes.

The possibility was examined that the membrane function of erythrocytes obtained from healthy common marmosets (Callithrix jacchus) was modified by the presence in the cells of Heinz bodies. No significant differences were found in erythrocyte endogenous free malonyl dialdehyde (MDA) or reduced glutathione (GSH) between normal human erythrocytes and marmoset erythrocytes containing Heinz bodies. Membrane fluorescent chromolipids, surface charge and thiol levels were similar in both species but average membrane bulk lipid fluidity was slightly elevated in the marmosets. It was concluded that, in contrast to the situation in human erythrocytes, the presence of Heinz bodies in red cells of marmosets does not adversely affect the properties of the membrane.

Animals↗