Comparative toxicity of netilmicin and gentamicin in squirrel monkeys (Saimiri sciureus).

Netilmicin was found to be less toxic than gentamicin when administered at comparable dosage levels to squirrel monkeys (Saimiri sciureus). This finding is based upon data obtained from the following determinations: length of survival period; change in body weight; observation of general change in behavior after daily injection; ataxia, as measured by the squirrel monkey platform-runway test; acoustic reflex threshold; levels of blood urea nitrogen and serum creatinine (and pathology of the kidney); and microbiological antibiotic assay.     

Plasma lipoprotein alterations in squirrel monkeys (Saimiri sciureus) during ethanol administration and abstinence

The time course of lipoprotein changes during ethanol (EtOH) consumption followed by abstinence was examined in 3 groups of male squirrel monkeys: 1) controls fed isocaloric liquid diet; 2) low EtOH monkeys given liquid diet with vodka substituted isocalorically for carbohydrate at 12% of calories; and 3) high EtOH animals fed diet plus vodka at 24% of calories. After 2 weeks, high EtOH monkeys showed significant elevations in total plasma cholesterol which continued to increase at 4 weeks and then declined at 8 weeks. These elevations were the result of increases in both low density (LDL)- and high density lipoprotein (HDL)-cholesterol. Low EtOH monkeys had a modest increase in total cholesterol throughout 8 weeks which was attributed to increments in HDL-cholesterol alone. During abstinence, total, HDL- and LDL-cholesterol concentrations decreased rapidly in the high EtOH group and were similar to control values after 4 days. HDL-cholesterol showed a more gradual decline in animals fed 12% EtOH while LDL-cholesterol remained low and not significantly different from controls. Liver function tests were normal for all animals. Our results indicate that low-dose EtOH favors a coronary protective lipoprotein profile (increases HDL, decreases LDL) in squirrel monkeys while the higher alcohol regimen causes both favorable and unfavorable alterations in plasma lipids which quickly revert to control levels during abstinence.     

Alcohol dose and low density lipoprotein heterogeneity in squirrel monkeys (Saimiri sciureus).

The present study was designed to determine whether normolipidemic male squirrel monkeys (Saimiri sciureus) exhibit low density lipoprotein (LDL) heterogeneity similar to that observed in humans and if present, whether LDL subfractions are altered by consumption of low vs. high dose ethanol (EtOH). Primates were divided into three groups designated control, low, and high EtOH and fed isocaloric liquid diets containing 0%, 12% and 24% of calories as EtOH, respectively, for 6 months. The 12% EtOH caloric level resulted in a modest, non-significant increase in high density lipoprotein (HDL) cholesterol and no change in LDL cholesterol or plasma apolipoprotein B (apo B), while the 24% dose produced significant elevations in plasma, LDL and HDL cholesterol and apo B. Using a single-spin density gradient ultracentrifugation procedure developed for humans, three distinct LDL subclasses designated LDL1a (d = 1.031 g/ml), LDL1b (d = 1.038 g/ml) and LDL 2 (d = 1.046 g/ml) were isolated from all three treatment groups. Monkey LDL subfractions were nearly identical to very light, light and heavy LDL subspecies isolated from human plasma in terms of their: (1) isopycnic densities following ultracentrifugation; (2) co-migration as single bands with beta-electrophoretic mobility in cellulose acetate and agarose electrophoretic gels; (3) size-dependent migration pattern in polyacrylamide gradient electrophoretic gels; (4) co-migration as a single band corresponding to apo B-100, following SDS polyacrylamide gel electrophoresis; and (5) decrease in total cholesterol/protein ratios with increasing LDL subclass density. Although there were no treatment differences in LDL particle size, within each treatment group, mean particle size for each LDL subfraction was significantly different from every other subfraction. Low (12%) dose alcohol had no effect on LDL subfraction mass relative to controls while high alcohol consumption resulted in marked increases in all lipid (except triglyceride) and protein of the larger, buoyant LDL subspecies (LDL1a and LDL1b). Moreover, the best correlation between plasma apo B and LDL subfraction total mass was demonstrated with LDL1b (r = 0.735). Since neither the lipid nor the protein concentration of the small, dense, purportedly more atherogenic, LDL2 changed with the 24% EtOH dose, we propose that the LDL subfraction alterations associated with high alcohol intake in squirrel monkeys (increased LDL1a, increased LDL1b, LDL2 no effect) may represent a compensatory response to modulate the overall atherogenic lipoprotein profile associated with elevations in total LDL cholesterol and plasma apolipoprotein B.     

Congenital Trypanosoma cruzi infection in a laboratory-born squirrel monkey, Saimiri sciureus

A Colombian Phenotype, laboratory-born squirrel monkey, Saimiri sciureus, was found to be congenitally infected with biologically proven Trypanosoma cruzi. The parasite was observed in blood smears and by xenodiagnoses of the mother and the offspring, and the isolates produced infection in mice and amastigotes in VERO tissue culture cells. The finding was accidental; both animals were healthy. Tissues of the mother did not show macro-microscopic evidence of T. cruzi infection and the electrocardiograph of the offspring was normal. This seems to be the first report of congenital T. cruzi transmission in an otherwise healthy non-human primate.     

The effects of light reinforcement and noise on young and old squirrel monkeys (Saimiri sciureus)

In two age groups of squirrel monkeys, subjects performed an operant response for light onset in the presence or absence of white noise. Results of the study indicate that light is an effective reinforcer for both younger and older monkeys, but differentially. The study also indicates that the presence of white noise affects responding in both age groups dissimilarly.     

Pathologic changes associated with fatal Plasmodium falciparum infection in the Bolivian squirrel monkey (Saimiri sciureus boliviensis)

Fatal cases of experimental Plasmodium falciparum (Indochina I) in Bolivian squirrel monkeys (Saimiri sciureus boliviensis) were examined by histologic and ultrastructural methods. Gross lesions were characterized by hepatosplenomegaly and interstitial pulmonary changes. Histologically, there was marked diffuse reticuloendothelial hyperplasia, pulmonary alveolar septal thickening, mesangioproliferative glomerulonephropathy, sequestration of parasitized erythrocytes in deep vascular beds, degenerative parenchymal changes in the liver and myocardium, and in one case retinal and cerebral hemorrhage. These data indicate that the Bolivian squirrel monkey is a good model for studying pathologic changes associated with human falciparum malaria.     

Chemotherapy of visceral leishmaniasis (Leishmania donovani) in the squirrel monkey (Saimiri sciureus)

The relationship of the numbers of amastigotes in the liver to the duration of infection with two lines of a Khartoum strain of Leishmania donovani [designated the parent (P) line and the meglumine antimoniate (Glucantime) resistant (MAR) line] and the effect of meglumine antimoniate on these two lines of Leishmania were studied in the squirrel monkey. All experimental monkeys were inoculated via the saphenous vein with 32.5 X 10(6) amastigotes (per kg body weight), obtained from heavily-infected hamster spleens. Subsequently in Experiment I, liver biopsy samples were taken chronologically from all monkeys. Imprints of liver were made on glass slides and stained with Giemsa's staining solution, and parasite density per gram of liver tissue was determined. The parasites reached a maximum density of 6.2 X 10(6) amastigotes per gram between two to four weeks and 9.4 X 10(7) amastigotes per gram between four to six weeks in the monkeys receiving the P line and the MAR line, respectively. Parasite numbers then decreased, and all the livers and spleens of all monkeys became microscopically negative for Leishmania eight to 13 weeks post-infection. Comparison of the multiplication of the two lines of Leishmania indicated that the MAR line persisted longer in the livers than did the P line. A slight decrease in body weight was observed at eight weeks post-infection. Packed cell volume and haemoglobin were low at four to eight weeks post-infection, but were within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hormonal response to stress in the squirrel monkey (Saimiri sciureus).

The pituitary-adrenal and gonadal responses following stress were evaluated in the squirrel monkey. Plasma levels of cortisol (CS), ACTH and testosterone (T) were determined during a 4-h period following the combined stress of capture and ether anesthesia. The results indicated that the squirrel monkey manifests higher basal levels of steroids than typically found in other mammals. The endocrine response following stress was biphasic, involving an initial elevation and subsequent decline in hormone levels. Males manifested significantly higher plasma levels of CS and T and lower plasma levels of ACTH than did females.     

In vitro and in vivo adaptation of the Geneve/SGE-1 strain of Plasmodium falciparum to growth in a squirrel monkey (Saimiri sciureus) model

Human erythrocytic culture-adapted parasites of the Geneve/SGE-1 strain of Plasmodium falciparum were successfully adapted to grow in an in vitro culture system containing squirrel monkey erythrocytes and serum. These monkey culture-adapted organisms were then used to produce a patent infection in a splenectomized squirrel monkey. Fresh infected blood from this animal was introduced into another splenectomized monkey and was subsequently serially passed through seven intact squirrel monkeys. High level parasitemias (greater than 10%) were obtained in the animals from the last two passes following inoculation of moderate numbers of parasites. It is anticipated that this squirrel monkey-adapted Geneve/SGE-1 strain of P. falciparum will continue to produce high level parasitemias in intact Bolivian Saimiri, and consequently will be suitable for challenge of these monkeys.     

Protective antibodies against erythrocytic stages of Plasmodium falciparum in experimental infection of the squirrel monkey, Saimiri sciureus

Serum and ascitic fluid from squirrel monkeys ( Saimiri sciureus ) inoculated with erythrocytic stages of Plasmodium falciparum were collected at different periods of the infection. Protection against P. falciparum was achieved by passive transfer of the sera or fluid recovered from animals after spontaneous or drug-induced cure. Purified immunoglobulins from the ascitic fluid also conferred protection. In contrast, protective antibodies directed against erythrocytic stages of P. falciparum could never be demonstrated during the acute phase of infection in spite of the high titres of malarial antibodies detected by immunofluorescence. The comparative immunochemical analysis of antigens recognized by protective and non-protective antibodies revealed quantitative differences which may be of use for the identification of antigens inducing protection.     

Light Suppression of Melatonin in the Squirrel Monkey (Saimiri sciureus)

This study examined plasma melatonin levels and the suppressant effect of light on melatonin production in the squirrel monkey. Monkeys were maintained on a 12:12 light-dark cycle (LD 12:12) with lights on from 07:00 to 19:00. Plasma levels of melatonin were determined by gas chromatography negative chemical ionization mass spectrometry. Melatonin levels at 00:00 (99.5 +/- 18.9 pg/ml) were significantly higher than at 02:00 (57.21 +/- 7.7 pg/ml; Student's t = 2.859; P less than or equal to 0.021). Baseline values at 02:00 were compared with levels at the same time of day after exposure to 2 hours of 200 lux of light (30.6 +/- 13.1 pg/ml), which caused an average suppression of 54.8% in melatonin levels. One animal did not show light suppression. Results indicated that the squirrel monkey suppressant response to light, as well as baseline values of melatonin, varied between animals.     

Neonatal rhesus monkeys as an animal model for rotavirus infection

AIM To establish a rotavirus(RV)-induced diarrhea model using RV SA11 in neonatal rhesus monkeys for the study of the pathogenic and immune mechanisms of RV infection and evaluation of candidate vaccines.METHODS Neonatal rhesus monkeys with an average age of 15-20 d and an average weight of 500 g ± 150 g received intragastric administration of varying doses of SA11 RV( 107 PFUs/mL, 106 PFUs/mL, or 105 PFUs/mL, 10 mL/animal) to determine whether the SA11 strain can effectively infect these animals by observing their clinical symptoms, fecal shedding of virus antigen by ELISA, distribution of RV antigen in the organs by immunofluorescence, variations of viral RNA load in the organs by qRT-PCR, histopathological changes in the small intestine by HE staining, and apoptosis of small intestinal epithelial cells by TUNEL assay.RESULTS The RV monkey model showed typical clinical diarrhea symptoms in the 108 PFUs SA11 group, where we observed diarrhea 1-4 d post infection(dpi) and viral antigen shed in the feces from 1-7 dpi. RV was found in jejunal epithelial cells. We observed a viral load of approximately 5.85 × 103 copies per 100 mg in the jejunum at 2 dpi, which was increased to 1.09 × 105 copies per 100 mg at 3 dpi. A relatively high viral load was also seen in mesenteric lymph nodes at 2 dpi and 3 dpi. The following histopathological changes were observed in the small intestine following intragastric administration of SA11 RV: vacuolization, edema, and atrophy. Apoptosis in the jejunal villus epithelium was also detectable at 3 dpi.CONCLUSION Our results indicate that we have successfully established a RV SA11 strain diarrhea model in neonatal rhesus monkeys. Future studies will elucidate the mechanisms underlying the pathogenesis of RV infection, and we will use the model to evaluate the protective effect of candidate vaccines.     

Inheritance of color vision in a New World monkey (Saimiri sciureus).

Squirrel monkeys (Saimiri sciureus) have a striking color-vision polymorphism; each animal has one of six different types of color vision. These arise from individual variation in the presence of three different middle- to long-wavelength cone pigments. The distribution of cone phenotypes was established for a large sample of squirrel monkeys, including several families, through analysis of a retinal gross potential. The results indicate that the inheritance of color vision in the squirrel monkey can be explained by assuming that the three middle- to long-wavelength cone pigments are specified by three alleles at a single locus on the X chromosome. This arrangement is discretely different from that found in Old World monkeys and humans.     

Increased HTLV type 1 tax specific CD8+ cells in HTLV type 1-asociated myelopathy/tropical spastic paraparesis: correlation with HTLV type 1 proviral load

Less than 1% of individuals infected with the human T lymphotropic virus type 1 (HTLV-1) develop an inflammatory neurological disorder, termed HTLV-1-associated myelopathy/tropical spastic (HAM/TSP), while the vast majority of those infected remain asymptomatic HTLV-1 carriers (ACs). The fundamental viroimmunological differences between these groups are not well understood. To address this issue, we have investigated HTLV-1-specific T cell responses and measured the proviral load in these groups. Frequencies of HTLV-1-specific CD8(+) cells were demonstrated to be significantly higher in HAM/TSP patients than in ACs by using intracellular cytokine staining and soluble divalent HLA-A2/Ig fusion protein loaded with HTLV-1 Tax 11-19 peptide. It is consistent with the observed increase in HTLV-1-specific cytotoxic T lymphocytes in HAM/TSP patients. These CD8(+) cells produced interferon (IFN)-gamma in recognition of HTLV-1 antigens bound to HLAs on the infected CD4(+) cells. Using phenotypic markers indicative for T cell differentiation, memory and/or effector HTLV-1 Tax-specific CD8(+) cells were found to be increased in HLA-A2 HAM/TSP patients. HTLV-1 proviral load was elevated in HAM/TSP patients when compared to ACs. In addition, the proviral load in HAM/TSP patients correlated with the frequency of HTLV-1-specific IFN-gamma(+)CD8(+) cells or Tax-HLA-A2/Ig(+)CD8(+) cells, especially with the effector cells. In contrast, the proviral load inversely correlated with memory cells. These results suggest that HTLV-1 antigens may continuously stimulate HTLV-1-specific CD8(+) cells and differentiate them from memory cells into effector cells in vivo. These differentiated HTLV-1-specific CD8(+) cells may play a role in the pathogenesis of HAM/TSP.     

Clinical manifestations associated with HTLV type I infection: a cross-sectional study

Human T-lymphotropic virus type I (HTLV-I) causes HTLV-I-associated myelopathy/tropical spastic paraparesis and adult T cell leukemia in a small percentage of infected individuals. HTLV-I infection is increasingly associated with clinical manifestations. To determine the prevalence of clinical manifestations in HTLV-I infected individuals, we conducted a cross-sectional study of 115 HTLV-I-infected blood donors without myelopathy and 115 age- and sex-matched seronegative controls. Subjects answered a standardized questionnaire and underwent physical examination. Compared with controls, HTLV-I-infected subjects were more likely to report arm or leg weakness (OR = 3.8, 95% CI: 1.4-10.2; OR = 4.0, 95% CI: 1.6-9.8, respectively), hand or foot numbness (OR = 2.1, 95% CI: 1.1-3.9; OR = 4.8, 95% CI: 2.0-11.7, respectively), arthralgia (OR = 3.3, 95% CI: 1.7-6.4), nocturia (OR = 2.7, 95% CI: 1.04-6.8), erectile dysfunction (OR = 4.0, 95% CI: 1.6-9.8), and to have gingivitis (OR = 3.8, 95% CI: 1.8-7.9), periodontitis (OR = 10.0, 95% CI: 2.3-42.8), and dry oral mucosa (OR = 7.5, 95% CI: 1.7-32.8). HTLV-I infection is associated with a variety of clinical manifestations, which may occur in patients who have not developed myelopathy.     

Hepatic encephalopathy in primary human immunodeficiency virus type 1 (HIV-1) infection

Primary infection of human immunodeficiency virus type 1 (HIV-1) is occasionally associated with common cold-like symptoms, and rarely with a self-limited illness resembling infectious mononucleosis. We report a 32-year-old man who presented with infectious mononucleosis-like blood picture on admission. Five days after admission he developed hepatic encephalopathy, which was ameliorated by administration of bolus corticosteroid. Based on the results of serologic studies, we diagnosed that he had primary HIV-1 infection. To our knowledge, this is the first published report of hepatic encephalopathy as a clinical manifestation of primary HIV-1 infection.