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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↗

The biobehavioral consequences of psychogenic stress in a small, social primate (Callithrix jacchus jacchus).

The biobehavioral consequences of psychogenic stress were examined using neuroendocrine and ethological methods in a captive colony of common marmosets (Callithrix jacchus jacchus). Specifically, hypothalamic-pituitary-adrenal (HPA) axis reactivity was evaluated as a function of gender and social status in four consecutive social environments [(1) stable heterosexual pairs; (2) isolation; (3) unstable peer groups; and (4) stable peer groups], by measuring both basal plasma cortisol, adrenocorticotropic hormone (ACTH) and beta-endorphin concentrations and responsiveness of these hormones to dexamethasone, ovine corticotropin-releasing hormone (oCRH), and ACTH1-24. Socially stressful conditions, such as isolation and peer group formation, were associated with increased HPA axis function and behavioral arousal, and individual profiles were related to gender and social status. Hormonal levels prior to group formation predicted subsequent status in peer groups. Basal morning concentrations of plasma cortisol, as well as cortisol responsiveness to dexamethasone suppression, were sensitive indices of HPA axis arousal during periods of social stress. The context-dependent development of hormonal and behavioral profiles, reminiscent of depression and/or anorexia nervosa, suggests that the common marmoset may be a useful model of psychiatric hypercortisolism.

Adrenocorticotropic Hormone↗

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↗

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↗

X-ray-induced translocations in marmoset (Callithrix jacchus) stem-cell spermatogonia.

The induction of reciprocal translocations in spermatogonial stem cells of marmosets (Callithrix jacchus) was studied after irradiation with different doses of X-rays (50, 100 and 200 rad) via spermatocyte analysis many cell generations later. The obtained results show a dose-effect relationship with clear saturation effects at 200 rad. The recorded frequencies of translocations were much lower than those reported for closely related marmosets (Saguinus fuscicollis and Saguinus oepidus). Possible reasons for this difference are discussed.

Animals↗

Visual optics and retinal cone topography in the common marmoset (Callithrix jacchus).

The common marmoset (Callithrix jacchus) is a small, diurnal, New World monkey amenable to vision research. In this paper we describe the visual optics and cone photoreceptor topography of the normal adult marmoset. Paraxial optical ray-tracing shows that the marmoset eye is well represented as a scaled-down version of the human eye. The density of foveal and perifoveal cone photoreceptors in the marmoset is as high, and in peripheral retina higher, than those reported in humans and macaques. The foveal acuity predicted by the Nyquist limits set by the cone mosaic (30 c/deg) is in agreement with behavioral measures of visual acuity. Foveal depth of focus is remarkably small (< 0.2 D) for an eye of this size (axial length about 11 mm). Estimates of the amplitude of accommodation using infrared photorefraction indicate that the marmoset is capable of more than 20 D of accommodation.

Animals↗

Ocular development and visual deprivation myopia in the common marmoset (Callithrix jacchus).

The normal postnatal ocular development of the common marmoset (Callithrix jacchus) and the effects of visual deprivation on eye growth and refractive state are described. The marmoset normally undergoes a developmental process of emmetropization from high hyperopia at birth. This emmetropization is easily disrupted by visual deprivation produced by lid-suture. Myopia and axial elongation of the vitreous chamber are induced by visual deprivations of 12, 5, and 3 weeks duration. The development of axial myopia after 3 weeks of visual deprivation differs from longer duration deprivations in that the experimental eyes are initially shorter than normal and hyperopic at the end of the visual deprivation period, but subsequently become longer than normal and myopic. Visual deprivation myopia in the marmoset persists even after the deprivation is discontinued and a visual signal is restored. In all experimental groups, the development of the eye in response to the cessation of visual deprivation shows no slowing of vitreous chamber enlargement; the axial enlargement relative to the control eye is either maintained or increases and produces significantly greater myopia. These results suggest that the visual control of postnatal eye growth in the marmoset may be unidirectional in its response to visual experience and able only to increase the growth rate of the vitreous chamber, possibly after an initial delay.

Animals↗

Behavioral effects of the intraventricular administration of 5-HT and dopamine in the common marmoset (Callithrix jacchus).

The effects of IVT serotonin [5-hydroxytryptamine (5-HT)] and dopamine (DA) administration have been studied in rats and marmosets (Callithrix jacchus). In rats, 5-HT (114 and 170 micrograms/10 microliters) produced the same behavioral effects observed after IP administration of its precursors and agonists. The same doses of 5-HT used for rats produced only part of the behavioral effects in marmosets after IP administration of 5-HT precursors and agonists. Ataxia, vomiting, and decreased motor activity were observed, but not drowsiness or teeth-chattering. However, IVT administration of DA (400 micrograms/10 microliters dose) produced head movements or checking, ataxia, tongue out, and decreased motor activity. These findings differ from those observed after IP administration of l-DOPA and DA agonists, which increase motor activity.

Animals↗

Fatal lymphoproliferative disease in a common marmoset (Callithrix jacchus) following inoculation of Ag876 strain of Epstein-Barr virus and a tumor-promoting agent: preliminary report.

We report here the development of a fatal lymphoproliferative disease in a common marmoset (Callithrix jacchus) following inoculation of the Ag876 strain of Epstein-Barr virus (EBV) and of the tumor promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA). The marmoset showed antibodies against EBV capsid and early antigens (VCA, EA) but not against nuclear antigen (EBNA). EBNA was detected in impression smears from lymph nodes and liver, and the presence of the EBV genome was detected from the same organs by hydridization techniques. To our knowledge this is the first report of the oncogenicity of this strain of EBV. The need for further studies to assess the in vivo interaction between EBV and tumor promoting agents in the development of malignancies is stressed.

Animals↗

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↗

Baseline and mitomycin C (MMC)-induced sister-chromatid exchanges in XX and XY cells of Callithrix jacchus chimeric twins.

Lymphocytes from chimeric individuals of the species Callithrix jacchus (Primates) were examined to evaluate differences in the frequency of sister chromatid exchanges (SCE) between XX and XY cells. The aim was to discover whether SCE differ according to genetic sex and whether XX and XY cells show a different sensitivity to SCE inducing agents. This experimental model has enabled us to eliminate the possible differences caused by environmental factors. The results obtained do not reveal significant differences between male and female cells, in either the baseline SCE frequency or that induced by mitomycin C at concentrations of 0.01 and 0.03 microgram/ml. No significant differences were observed in the distribution of high SCE frequency cells (HFC), even if it is possible to observe a higher level of exchanges in XX cells in each trial. With regard to the phenotypic sex, there appears to be a trend towards slightly higher SCE rates in females, even if results are not statistically significant.

Animals↗

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↗

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↗

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↗

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↗

Urinary estradiol-17 beta excretion in common marmosets, Callithrix jacchus: diurnal pattern and relationship between creatinine-related values and excreted amount.

1. The diurnal pattern of urinary estradiol and creatinine excretion was investigated in order to evaluate the relationship between total estradiol excretion per day and the estradiol concentration or the estradiol-to-creatinine ratio from single urine samples in female common marmosets (Callithrix j. jacchus). 2. During a 36-day period, urine was collected from five adult female marmosets in 3-hr intervals during the light time of an LD 12:12 (400:0.1 lx) which corresponded to the animals' activity time. 3. Estradiol concentration was determined by radioimmunoassay after glucuronidase treatment and creatinine concentration was measured photometrically. 4. Concentration and amount of excreted estradiol, and the creatinine concentration showed a distinct diurnal pattern with significantly higher levels at the beginning of the activity time compared to later sampling times. 5. No diurnal pattern was present in the estradiol-to-creatinine ratio, but the difference between lower follicular and higher luteal phase levels of estradiol excretion remained significant in the 36-day period. 6. Correlation analyses revealed significantly positive correlations between the total estrogen mass excreted per day and the estradiol-to-creatinine ratio in "morning urine" samples. 7. Thus the estradiol-to-creatinine ratio of single urine samples collected at the beginning of the activity time provides a reliable estimate of total estrogenic output in this species. 8. Studies of the circadian pattern of urinary hormone excretion, however, require total urine sampling.

Animals↗

The digestive strategy of the common marmoset, Callithrix jacchus.

Digestive tract morphology and function were studied in the common marmoset (Callithrix jacchus), a small (350 g) exudivore with a well-developed caecum. Transit times (times of first appearance of the markers in the faeces following a pulse dose in the food) were similar for Co-EDTA, which marks the fluid phase of the digesta, and Cr-mordanted cell walls, which marked the large (600-1200 microns) particulate phase of the digesta. However, mean retention time (the average time taken for the markers to transverse the whole digestive tract) for Co-EDTA was significantly longer than for Cr-cell walls, indicating selective retention of fluid digesta relative to large particles, probably in the caecum. These data are consistent with a digestive strategy of the common marmoset that appears to be based on rapid digestion of higher quality foods (animal prey, fruits) in the small intestine, followed by microbial fermentation of the complex polysaccharides of plant exudates in the caecum, which would allow for considerable dietary flexibility in its natural habitat of scrub forests.

Animals↗

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↗