Increase in micronucleated erythrocytes associated with babesiosis in Syrian golden hamsters

The effect of infection by Babesia microti, a tick-borne piroplasm endemic to the northeastern United States, on the temporal pattern of micronucleated erythrocyte frequencies in peripheral blood was investigated in male Syrian golden hamsters. Significantly greater frequencies of micronucleated erythrocytes occurred in the blood of infected hamsters from 26 to 46 days after injection with B. microti, the magnitude of which within individual hamsters correlated highly with the percentage of polychromatic erythrocytes and the extent of parasitization. These data suggest that parasitic infection and other factors which alter the rate of erythropoiesis should be considered when the micronucleus assay is used in environmental or laboratory studies of genetic toxicity.     

Severe acute respiratory syndrome coronavirus infection of golden Syrian hamsters

Small animal models are needed in order to evaluate the efficacy of candidate vaccines and antivirals directed against the severe acute respiratory syndrome coronavirus (SARS CoV). We investigated the ability of SARS CoV to infect 5-week-old Golden Syrian hamsters. When administered intranasally, SARS CoV replicates to high titers in the lungs and nasal turbinates. Peak replication in the lower respiratory tract was noted on day 2 postinfection (p.i.) and was cleared by day 7 p.i. Low levels of virus were present in the nasal turbinates of a few hamsters at 14 days p.i. Viral replication in epithelial cells of the respiratory tract was accompanied by cellular necrosis early in infection, followed by an inflammatory response coincident with viral clearance, focal consolidation in pulmonary tissue, and eventual pulmonary tissue repair. Despite high levels of virus replication and associated pathology in the respiratory tract, the hamsters showed no evidence of disease. Neutralizing antibodies were detected in sera at day 7 p.i., and mean titers at day 28 p.i. exceeded 1:400. Hamsters challenged with SARS CoV at day 28 p.i. were completely protected from virus replication and accompanying pathology in the respiratory tract. Comparing these data to the mouse model, SARS CoV replicates to a higher titer and for a longer duration in the respiratory tract of hamsters and is accompanied by significant pathology that is absent in mice. Viremia and extrapulmonary spread of SARS CoV to liver and spleen, which are seen in hamsters, were not detected in mice. The hamster, therefore, is superior to the mouse as a model for the evaluation of antiviral agents and candidate vaccines against SARS CoV replication.     

Spontaneous seizures: a new mutation in Syrian golden hamsters.

Hereditary spontaneous seizures in the Syrian hamsters are described. The seizures occur in 30 to 60-day-old animals from about 2 to 5 hours. The condition is a simple recessive trait, and the gene symbol sz is proposed.     

A live attenuated severe acute respiratory syndrome coronavirus is immunogenic and efficacious in golden Syrian hamsters

The immunogenicity and protective efficacy of a live attenuated vaccine consisting of a recombinant severe acute respiratory syndrome (SARS) coronavirus lacking the E gene (rSARS-CoV-ΔE) were studied using hamsters. Hamsters immunized with rSARS-CoV-ΔE developed high serum-neutralizing antibody titers and were protected from replication of homologous (SARS-CoV Urbani) and heterologous (GD03) SARS-CoV in the upper and lower respiratory tract. rSARS-CoV-ΔE-immunized hamsters remained active following wild-type virus challenge, while mock-immunized hamsters displayed decreased activity. Despite being attenuated in replication in the respiratory tract, rSARS-CoV-ΔE is an immunogenic and efficacious vaccine in hamsters.     

Ontogeny of endocrine cells in the respiratory system of Syrian golden hamsters

The ontogeny of protein gene product 9.5 (PGP 9.5), serotonin (5-HT), calcitonin gene-related peptide (CGRP), and calcitonin (CT) immunoreactivity was evaluated in small-granule endocrine cells of hamster laryngotracheal epithelium from fetal day 11 to adulthood. Two centrifugal (proximal-to-distal) patterns of differentiation occur. The first pattern begins during fetal life. Endocrine cells, single and clustered in groups (presumptive-or protoneuroepithelial bodies, pNEBs), initially colocalize immunostaining for PGP 9.5, 5-HT, and CGRP in the larynx and proximal 2/3 of the trachea on day 12 and spread to the caudal trachea on day 13.5-HT disappears fleetingly during the 24 h preceding birth; other-wise immunoreactivity for all three substances persists into adulthood. The clusters of endocrine cells survive beyond birth but are so diluted by expansion of the nonendocrine epithelium as to become inconspicuous. Since innervation was not actually observed, these clusters may persist as pNEBs, without developing connections to afferent or efferent nerve fibers. The second pattern concerns single small-granule cells stainable for CGRP but not for 5-HT. These cells first appear in the larynx and cartilaginous part of the cranial trachea on postnatal day 3, and in the middle and caudal trachea, on day 5. The cells increase in number on day 7. In adults, they predominate among endocrine cells of the cartilaginous region. A subset of these cells begins to co-express CT proximally on postnatal day 10, reaching the caudal end of the trachea by 3 weeks. A few elements of the older 5-HT-positive population may also become immunoreactive for CT in juvenile hamsters.     

Dehydroepiandrosterone-induced reduction of Cryptosporidium parvum infections in aged Syrian golden hamsters.

Cryptosporidiosis, a parasitic disorder caused by Cryptosporidium parvum, is frequently a fulminating and life-threatening disease in immunocompromised hosts. The immune status of the host plays a critical role in determining the length and severity of the disease. Dehydroepiandrosterone (DHEA) is an immunomodulator that has been demonstrated to upregulate immune parameters. Ten aged (20-24 mo) Syrian golden hamsters were treated with DHEA for 7 days prior to intragastric inoculation with 1 x 10(6) C. parvum oocysts. An additional 10 aged hamsters were infected similarly but retained as untreated controls. The untreated hamsters presented with generalized infections as determined by oocyst shedding in the feces and parasite colonization of the small intestine. Hamsters treated with DHEA exhibited a significant reduction in cryptosporidial infection when compared to untreated hamsters. These results suggest that DHEA may be an effective prophylactic agent for cryptosporidiosis in immunocompromised patients.     

Ontogeny of endocrine cells in the respiratory system of Syrian golden hamsters

The ontogeny of protein gene product 9.5 (PGP 9.5), serotonin (5–HT), calcitonin gene-related peptide (CGRP), and calcitonin (CT) immunoreactivity was evaluated in small-granule endocrine cells of hamster laryngotracheal epithelium from fetal day 11 to adulthood. Two centrifugal (proximal-to-distal) patterns of differentiation occur. The first pattern begins during fetal life. Endocrine cells, single and clustered in groups (presumptive- or protoneuroepithelial bodies, pNEBs), initially co-localize immunostaining for PGP 9.5, 5–HT, and CGRP in the larynx and proximal 2/3 of the trachea on day 12 and spread to the caudal trachea on day 13. 5–HT disappears fleetingly during the 24 h preceding birth; otherwise immunoreactivity for all three substances persists into adulthood. The clusters of endocrine cells survive beyond birth but are so diluted by expansion of the nonendocrine epithelium as to become inconspicuous. Since innervation was not actually observed, these clusters may persist as pNEBs, without developing connections to afferent or efferent nerve fibers. The second pattern concerns single small-granule cells stainable for CGRP but not for 5–HT. These cells first appear in the larynx and cartilaginous part of the cranial trachea on postnatal day 3, and in the middle and caudal trachea, on day 5. The cells increase in number on day 7. In adults, they predominate among endocrine cells of the cartilaginous region. A subset of these cells begins to co-express CT proximally on postnatal day 10, reaching the caudal end of the trachea by 3 weeks. A few elements of the older 5–HT-positive population may also become immunoreactive for CT in juvenile hamsters.     

Hydroxycinnamic acids do not prevent aortic atherosclerosis in hypercholesterolemic golden Syrian hamsters

The protective effect of hydroxycinnamic acids, i.e. caffeic acid (CA) and sinapic acid (SA) present in wine, and chlorogenic acid (CHA) present in apple, compared to a red wine phenolic extract (RWPE) was investigated in hamsters fed an atherogenic diet for 12 weeks. Five groups of 8 hamsters fed such a diet received by force-feeding RWPE, CA or SA in water, mimicking a moderate consumption of alcohol-free red wine. Controls received water and CHA force-feeding was extrapolated from apple consumption. Plasma cholesterol concentration was lower in group that received RWPE (-22%) and hydroxycinnamic acids had no effect. Plasma apolipoprotein Apo-A1 concentration was not affected; consumption of RWPE only decreased Apo-B concentration (-46%). Liver superoxide dismutase activity was 33% lower and glutathione peroxidase activity was 67% greater in the group receiving RWPE compared to controls; there was no effect when CA, SA or CHA were given. All the phenolic compounds significantly increased plasma antioxidant capacity (about 28% on average) compared with controls. Aortic fatty streak area was significantly reduced in the group receiving RWPE (-30%) in comparison with controls and hydroxycinnamic acids. Our findings demonstrate that chronic ingestion of the nonalcoholic components of red wine, mainly polyphenols, prevent the development of atherosclerosis in hamster and that wine hydroxycinnamic acids are not the phenolic compounds involved in such a beneficial effect.     

Anacetrapib promotes reverse cholesterol transport and bulk cholesterol excretion in Syrian golden hamsters

Cholesteryl ester transfer protein (CETP) transfers cholesteryl ester (CE) and triglyceride between HDL and apoB-containing lipoproteins. Anacetrapib (ANA), a reversible inhibitor of CETP, raises HDL cholesterol (HDL-C) and lowers LDL cholesterol in dyslipidemic patients; however, the effects of ANA on cholesterol/lipoprotein metabolism in a dyslipidemic hamster model have not been demonstrated. To test whether ANA (60 mg/kg/day, 2 weeks) promoted reverse cholesterol transport (RCT), 3H-cholesterol-loaded macrophages were injected and (3)H-tracer levels were measured in HDL, liver, and feces. Compared to controls, ANA inhibited CETP (94%) and increased HDL-C (47%). 3H-tracer in HDL increased by 69% in hamsters treated with ANA, suggesting increased cholesterol efflux from macrophages to HDL. 3H-tracer in fecal cholesterol and bile acids increased by 90% and 57%, respectively, indicating increased macrophage-to-feces RCT. Mass spectrometry analysis of HDL from ANA-treated hamsters revealed an increase in free unlabeled cholesterol and CE. Furthermore, bulk cholesterol and cholic acid were increased in feces from ANA-treated hamsters. Using two independent approaches to assess cholesterol metabolism, the current study demonstrates that CETP inhibition with ANA promotes macrophage-to-feces RCT and results in increased fecal cholesterol/bile acid excretion, further supporting its development as a novel lipid therapy for the treatment of dyslipidemia and atherosclerotic vascular disease.     

Soyasaponins lowered plasma cholesterol and increased fecal bile acids in female golden Syrian hamsters

A study was conducted in hamsters to determine if group B soyasaponins improve plasma cholesterol status by increasing the excretion of fecal bile acids and neutral sterols, to identify group B soyasaponin metabolites, and to investigate the relationship between a fecal group B soyasaponin metabolite and plasma lipids. Twenty female golden Syrian hamsters, 11-12 weeks old and 85-125 g, were randomly assigned to a control diet or a similar diet containing group B soyasaponins (containing no isoflavones), 2.2 mmol/kg, for 4 weeks. Hamsters fed group B soyasaponins had significantly lower plasma total cholesterol (by 20%), non-high-density lipoprotein (HDL) cholesterol (by 33%), and triglycerides (by 18%) compared with those fed casein (P < 0.05). The ratio of total cholesterol to HDL cholesterol was significantly lower (by 13%) in hamsters fed group B soyasaponins than in those fed casein (P < 0.05). The excretion of fecal bile acids and neutral sterols was significantly greater (by 105% and 85%, respectively) in soyasaponin-fed hamsters compared with those fed casein (P < 0.05). Compared with casein, group B soyasaponins lowered plasma total cholesterol levels and non-HDL cholesterol levels by a mechanism involving greater excretion of fecal bile acids and neutral sterols. Hamsters fed group B soyasaponins statistically clustered into two fecal soyasaponin metabolite-excretion phenotypes: high excreters (n = 3) and low excreters (n = 7). When high and low producers of this soyasaponin metabolite were compared for plasma cholesterol status, the high producers showed a significantly lower total-cholesterol-to-HDL-cholesterol ratio compared with the low producers (1.38 +/- 0.7 vs. 1.59 +/- 0.13; P < 0.03). Greater production of group B soyasaponin metabolite in hamsters was associated with better plasma cholesterol status, suggesting that gut microbial variation in soyasaponin metabolism may influence the health effects of group B soyasaponins.     

Electrophysiological studies on the cultured cells obtained from transplantable pancreatic carcinoma in Syrian golden hamsters

A pancreatic ductal carcinoma was established as a transplantable tumor line in an inbred strain of Syrian golden hamsters. Intracellular recordings of membrane potentials and input resistance were made from cultured cells obtained from the transplanted tumors using indwelling glass microelectrode. The mean value of the resting membrane potential was -46.5 +/- 1.8 mV (S.E.) (n = 13), while the mean resting input resistance was 21.2 +/- 4.3 M omega (S.E.) (N = 13). Dibutyryl cyclic AMP (2 X 10(-3)M) caused a marked hyperpolarization of about 30 mV accompanied by a reduction of input resistance. The transplantable tumor and its cultured cell line developed in this study have demonstrated their effectiveness as a reliable experimental model for use in pancreatic cancer research.     

Volitional ethanol consumption affects overall serotonin metabolism in Syrian golden hamsters (Mesocricetus auratus)

Methods were established for the determination of serotonin (5-HT)(1) metabolites 5-hydroxyindole-3-acetic acid (5-HIAA) and 5-hydroxytryptophol (5-HTOL) in the urine of Syrian golden hamsters (Mesocricetus auratus) and used to study the effect of volitional ethanol consumption on overall 5-HT metabolism in this ethanol-preferring rodent. The basal levels of 5-HIAA and 5-HTOL in 24-h urine of ethanol-naive hamsters were 300 +/- 101 and 4.96 +/- 1. 06 nmol (n = 8), respectively. Given free choice between water and a 15% ethanol solution, these hamsters chose to consume increasing amounts of ethanol. The increase was accompanied by a concomitant decrease in urine 5-HIAA and increase in urine 5-HTOL, indicating that volitional ethanol intake diverted part of the 5-HT metabolic flux from an oxidative into a reductive pathway. In a separate experiment, the amounts of ethanol consumed by and blood ethanol concentrations attained in ethanol-drinking golden hamsters were determined at 5 different time intervals between 6 PM and 7 AM when most feeding activities occurred. Except in the first hour after lights were turned off, ethanol was consumed at a relatively even pace throughout the night (2-3 g/kg/3 h) and blood ethanol levels were maintained at the low mM range which rarely exceeded 2 mM. These results suggest that the biochemical pathway that catalyzes 5-HT metabolism is extremely sensitive to ethanol and can play an important role in mediating the reported clinically beneficial action of a low concentration of ethanol during alcohol detoxification.