Schistosoma mansoni infection affects the proteome and lipidome of circulating extracellular vesicles in the host.

Eggs, schistosomula and adult Schistosoma worms are known to release extracellular vesicles (EV) during in vitro incubations and these EVs are postulated to affect the host responses. So far only those EVs released during in vitro incubations of schistosomes have been studied and it is unknown whether in blood of infected hosts the schistosomal EVs can be detected amidst all the circulating EVs of the host itself. In this study we analyzed the protein as well as the phospholipid composition of EVs circulating in blood plasma of S. mansoni infected hamsters and compared those with the EVs circulating in blood of non-infected hamsters. Although neither proteins nor lipids specific for schistosomes could be detected in the circulating EVs of the infected hamsters, the infection with schistosomes had a marked effect on the circulating EVs of the host, as the protein as well as the lipid composition of EVs circulating in infected hamsters were different from the EVs of uninfected hamsters. The observed changes in the EV lipid and protein content suggest that more EVs are released by the diseased liver, the affected erythrocytes and activated immune cells.

Male-specific pulmonary hemorrhage and cytokine gene expression in golden hamster in early-phase Leptospira interrogans serovar Hebdomadis infection.

Leptospirosis causes severe clinical signs more frequently in men than in women, but the mechanism underlying the gender differences in leptospirosis remains unclear. In this study, petechial hemorrhage was observed in male but not in female hamster lung tissues infected with Leptospira interrogans serovar Hebdomadis at 120 h pi, demonstrating that male hamsters were more susceptible to the development of a severe disease upon Leptospira infection. No leptospiral DNA was detected in the lung tissues at 120 h pi when pulmonary hemorrhage was observed, indicating that pulmonary hemorrhage is attributable to the immune reactions of the host rather than from the direct effect of leptospires. The upregulation of nitric oxide synthase genes in the hamsters without pulmonary hemorrhage, inos and enos in female hamsters at 96 h pi and enos in male animals without hemorrhage at 120 h pi, may suggest that nitric oxide has a suppressive effect on leptospirosis-associated pulmonary hemorrhage.

Comparison of Bacterial Burden and Cytokine Gene Expression in Golden Hamsters in Early Phase of Infection with Two Different Strains of Leptospira interrogans.

Leptospirosis, a zoonotic infection with worldwide prevalence, is caused by pathogenic spirochaetes of Leptospira spp., and exhibits an extremely broad clinical spectrum in human patients. Although previous studies indicated that specific serovars or genotypes of Leptospira spp. were associated with severe leptospirosis or its outbreak, the mechanism underlying the difference in virulence of the various Leptospira serotypes or genotypes remains unclear. The present study addresses this question by measuring and comparing bacterial burden and cytokine gene expression in hamsters infected with strains of two L. interrogans serovars Manilae (highly virulent) and Hebdomadis (less virulent). The histopathology of kidney, liver, and lung tissues was also investigated in infected hamsters. A significantly higher bacterial burden was observed in liver tissues of hamsters infected with serovar Manilae than those infected with serovar Hebdomadis (p < 0.01). The average copy number of the leptospiral genome was 1,302 and 20,559 in blood and liver, respectively, of hamsters infected with serovar Manilae and 1,340 and 4,896, respectively, in hamsters infected with serovar Hebdomadis. The expression levels of mip1alpha in blood; tgfbeta, il1beta, mip1alpha, il10, tnfalpha and cox2 in liver; and tgfbeta, il6, tnfalpha and cox2 in lung tissue were significantly higher in hamsters infected with serovar Manilae than those infected with serovar Hebdomadis (p < 0.05). In addition, infection with serovar Manilae resulted in a significantly larger number of hamsters with tnfalpha upregulation (p = 0.04). Severe distortion of tubular cell arrangement and disruption of renal tubules in kidney tissues and hemorrhage in lung tissues were observed in Manilae-infected hamsters. These results demonstrate that serovar Manilae multiplied more efficiently in liver tissues and induced significantly higher expression of genes encoding pro- and anti-inflammatory cytokines than serovar Hebdomadis even in tissues for which a significant difference in leptospiral load was not observed. In addition, our results suggest a serovar Manilae-specific mechanism responsible for inducing severe damage in kidneys and hemorrhage in lung.

Blood Lipid Distribution, Aortic Cholesterol Concentrations, and Selected Inflammatory and Bile Metabolism Markers in Syrian Hamsters Fed a Standard Breeding Diet.

Hamsters are often used to determine the effects of various dietary ingredients on the development of cardiovascular disease (CVD). The study was conducted to obtain baseline data on CVD risk factors and mRNA expression of selected genes in hamsters fed a standard maintenance diet (STD) for 24 wk, beginning when animals were 7 wk old. Plasma triacylglycerol and aortic cholesteryl ester concentrations did not significantly change during the study. Total plasma cholesterol (75.9-127.9 mg/dL), LDL- (3.2-12.2 mg/dL), and HDL- (53.8-98.9 mg/dL) cholesterols increased over the 24wk study. Aortic total cholesterol increased from 9.72 to 12.20 µg/mg protein, whereas aortic cholesteryl ester, a measure of atherosclerosis development, was less than 0.18 µg/mg protein throughout the study. The expression of hepatic endothelin 1, peroxisome proliferator-activated receptor α, and hepatic cholesterol 7-α-hydroxylase mRNA did not change throughout the study, indicating that fatty acid ß-oxidation and cholesterol metabolism remained consistent. The mRNA expression of ATP-binding cassette, subfamily B member 11 increased between wk 0 and 8 but then remained unchanged, suggesting increased requirements for cholesterol in early growth. These results indicate that the consumption of a STD does not increase atherosclerotic disease risk factors in golden Syrian hamsters through 31 wk of age.

Single-dose live-attenuated Nipah virus vaccines confer complete protection by eliciting antibodies directed against surface glycoproteins.

BACKGROUND: Nipah virus (NiV), a zoonotic pathogen causing severe respiratory illness and encephalitis in humans, emerged in Malaysia in 1998 with subsequent outbreaks on an almost annual basis since 2001 in parts of the Indian subcontinent. The high case fatality rate, human-to-human transmission, wide-ranging reservoir distribution and lack of licensed intervention options are making NiV a serious regional and potential global public health problem. The objective of this study was to develop a fast-acting, single-dose NiV vaccine that could be implemented in a ring vaccination approach during outbreaks. METHODS: In this study we have designed new live-attenuated vaccine vectors based on recombinant vesicular stomatitis viruses (rVSV) expressing NiV glycoproteins (G or F) or nucleoprotein (N) and evaluated their protective efficacy in Syrian hamsters, an established NiV animal disease model. We further characterized the humoral immune response to vaccination in hamsters using ELISA and neutralization assays and performed serum transfer studies. RESULTS: Vaccination of Syrian hamsters with a single dose of the rVSV vaccine vectors resulted in strong humoral immune responses with neutralizing activities found only in those animals vaccinated with rVSV expressing NiV G or F proteins. Vaccinated animals with neutralizing antibody responses were completely protected from lethal NiV disease, whereas animals vaccinated with rVSV expressing NiV N showed only partial protection. Protection of NiV G or F vaccinated animals was conferred by antibodies, most likely the neutralizing fraction, as demonstrated by serum transfer studies. Protection of N-vaccinated hamsters was not antibody-dependent indicating a role of adaptive cellular responses for protection. CONCLUSIONS: The rVSV vectors expressing Nipah virus G or F are prime candidates for new 'emergency vaccines' to be utilized for NiV outbreak management.

Twice daily melatonin peaks in Siberian but not Syrian hamsters under 24 h light:dark:light:dark cycles.

The daily pattern of blood-borne melatonin varies seasonally under the control of a multi-oscillator circadian pacemaker. Here we examine patterns of melatonin secretion and locomotor activity in Siberian and Syrian hamsters entrained to bimodal LDLD8:4:8:4 and LD20:4 lighting schedules that facilitate novel temporal arrangements of component circadian oscillators. Under LDLD, both species robustly bifurcated wheel-running activity in distinct day scotophase (DS) and night scotophase (NS) bouts. Siberian hamsters displayed significant melatonin increases during each scotophase in LDLD, and in the single daily scotophase of LD20:4. The bimodal melatonin secretion pattern persisted in acutely extended 16 h scotophases. Syrian hamsters, in contrast, showed no significant increases in plasma melatonin during either scotophase of LDLD8:4:8:4 or in LD20:4. In this species, detectable levels were observed only when the DS of LDLD was acutely extended to yield 16 h of darkness. Established species differences in the phase lag of nocturnal melatonin secretion relative to activity onset may underlie the above contrast: In non-bifurcated entrainment to 24 h LD cycles, Siberian hamsters show increased melatonin secretion within ≈ 2 h after activity onset, whereas in Syrian hamsters, detectable melatonin secretion phase lags activity onset and the L/D transition by at least 4 h. The present results provide new evidence indicating multi-oscillator regulation of the waveform of melatonin secretion, specifically, the circadian control of the onset, offset and duration of nocturnal secretion.

Maturation of social reward in adult male Syrian hamsters does not depend on organizational effects of pubertal testosterone.

The rewarding value of female sexual stimuli develops across puberty, as sexually-naïve adult, but not prepubertal, male hamsters show a conditioned place preference (CPP) for both vaginal secretions and a receptive female. Similarly, only adults show an endogenous testosterone surge when they encounter vaginal secretions. Testosterone by itself can condition a place preference in male rodents. Therefore, Experiment 1 assessed whether the endogenous testosterone surge elicited by vaginal secretions is necessary to show a CPP. Both gonad-intact and gonadectomized, testosterone-treated adult males showed a CPP for vaginal secretions, indicating that the rewarding value of this social cue is independent of an endogenous testosterone surge. However, organizational effects of pubertal testosterone could be necessary for adolescent development of social reward, as pubertal testosterone organizes adult-typical expression of sexual behavior. To investigate this possibility, in Experiment 2, sexually-naïve prepubertal and adult male hamsters were gonadectomized and received testosterone-filled capsules four weeks later. Testing began after two weeks of testosterone replacement. Adult males showed a CPP for both vaginal secretions and a receptive female, whether or not they experienced pubertal testosterone. Thus, the acquisition of positive valence of sexual stimuli is not organized by pubertal testosterone. Taken together, the ability of female sexual stimuli to serve as an unconditioned reward to adult male hamsters is independent of the chemosensory-induced endogenous testosterone surge and also organizational effects of pubertal testosterone. Instead, sexual reward may be dependent either on activational effects of testosterone or gonadal hormone-independent mechanisms.

[Continuous blood coagulation in chronic opisthorchiasis].

Animal experiments have shown that chronic Opisthorchis invasion results in accelerated continuous blood coagulation, by inducing hypercoagulation and platelet activation. The state of hemostasis depends on the degree of infection and undergoes the largest changes during maximum invasion. Irrespective of invasion rates, chronic opisthorchiasis is accompanied by hypofibrinogenemia.

Effects of ivermectin on blood-feeding Phlebotomus papatasi, and the promastigote stage of Leishmania major.

Ivermectin (IVM) is a chemically modified macrocyclic lactone of Streptomyces avermitilis that acts as a potent neurotoxin against many nematodes and arthropods. Little is known of IVM's effect against either blood-feeding Phlebotomus sand flies, or the infective promastigote stage of Leishmania transmitted by these flies. We injected hamsters subcutaneously with two standard IVM treatments (200 and 400 µg/kg body weight) and allowed cohorts of Leishmania major-infected Phlebotomus papatasi to blood-feed on these animals at various posttreatment time points (4 h, 1, 2, 6, and 10 days). Infected and uninfected sand flies that bit treated and untreated hamsters served as controls. Serum levels of IVM in low- and high-dose-treated hamsters were determined at the five time points. Sand fly mortality following blood feeding was recorded at 24-h intervals and, in relation to IVM treatment, was time and dose dependent. Mortality was most rapid and greatest among infected flies that fed nearest to time of dosing. Mean survival of infected sand flies after feeding on untreated hamsters was 11.5 days, whereas that of infected sand flies that fed 4 h, 1 day, or 2 days posttreatment on high-dose-treated hamsters (400 µg/kg) was 1.6, 2.1, and 2.7 days, respectively. Infected and uninfected sand flies that blood fed 6 days following low-dose IVM treatment (200 µg/kg) still experienced significantly greater mortality (p < 0.02) than controls. Promastigotes dissected out of surviving flies that fed on IVM-treated hamsters showed typical motility and survival. Moreover, 21.7% of IVM-treated hamsters developed lesions after being fed upon by infected sand flies. L. major promastigotes appeared to be tolerant to ng/mL blood levels of IVM that caused significant mortality for up to 10 days posttreatment in blood-feeding P. papatasi.

Blood collection from the sublingual vein in mice and hamsters: a suitable alternative to retrobulbar technique that provides large volumes and minimizes tissue damage.

Blood examination is a key element in studies of laboratory animals. In rodents, retrobulbar venous plexus puncture is a commonly used method for obtaining a blood sample. Although this technique yields large volumes of blood, the disadvantage is that it can lead to severe tissue damage. The aim of the present study was to develop the puncture of V. sublingualis as a suitable alternative technique for drawing blood in mice and other rodents. In rats, this method has been established for collecting large blood volumes. During the first part of the study, the sublingual bleeding technique was developed for use in mice and hamsters. Guinea pigs, however, do not have a sublingual vein; therefore, in this species the method is not possible. In the second part of the study, retrobulbar and sublingual methods were compared using male CD-1 mice. When compared with the retrobulbar method, sublingual venepuncture showed less tissue destruction in mice, with a decreased mean severity in the histological examination. In conclusion, sublingual venepuncture can be recommended as a suitable, alternative blood collection technique, because of the reduced risk of tissue damage in mice and hamsters.

The duration of capture and restraint during anesthesia and euthanasia influences glucocorticoid levels in male golden hamsters.

Deep litter has been shown to decrease stereotypic wire-gnawing in male golden hamsters, suggesting that increased litter depth may be associated with decreased chronic stress levels. To determine the relationship between litter depth and stress levels in hamsters, the authors measured serum levels of corticosterone, cortisol, and ACTH in male golden hamsters kept in cages with three different depths of litter. The duration of handling the hamsters significantly increased the concentrations of corticosterone, cortisol, and the ratio of cortisol/corticosterone. It took longer to catch hamsters housed in cages with deep litter and the ACTH levels were higher in these hamsters. The positive effect of the enrichment (deep litter) was diminished by methodological problems during handling/anesthesia.

High-density lipoproteins (HDL) inhibit endotoxin-induced leukocyte adhesion on endothelial cells in rats: effect of the acute-phase HDL.

High-density lipoprotein (HDL) plays an important role not only in protecting against atherosclerosis but also in innate immunity. Several lines of evidence showed that HDL could ameliorate the toxic effects of endotoxin or lipopolysaccharide (LPS). In this study, we examined whether HDL could inhibit LPS-induced leukocyte adhesion on endothelial cells in rats. Normal HDL and acute-phase HDL (AP-HDL) were purified from plasma of hamsters that received normal saline and LPS injection, respectively. Wistar rats were given LPS injection and the number of leukocytes adhering to endothelial cells of the mesenteric venules was determined using intravital fluorescence videomicroscopy. Intravenous injection of LPS enhanced leukocyte adhesion to the mesenteric venules. However, when LPS was preincubated with normal HDL, leukocyte adhesion on endothelial cells in response to LPS was significantly attenuated in a dose-dependent manner. AP-HDL was also able to significantly decrease LPS-induced leukocyte adhesion on endothelial cells. It appeared to be more effective than normal HDL since lower concentrations were required. This inhibitory effect of HDL was not due to HDL itself but it requires preincubation of HDL with LPS. When HDL was separated into protein and lipid fractions, it was found that lipid-free apoHDL was able to significantly inhibit LPS-induced leukocyte adhesion, whereas lipid component of HDL had no effect. In conclusion, HDL, both normal and acute-phase, could inhibit an inflammatory effect of LPS on endothelial cells in vivo. AP-HDL was more potent than normal HDL in inhibiting LPS-induced leukocyte adhesion, and this effect was attributed to the protein component of HDL.

Activated clotting time and heparin administration in Sprague-Dawley rats and Syrian golden hamsters.

To determine the activated clotting time (ACT) in rats and hamsters from our colony and to evaluate the response of this parameter to different heparin doses in these species, ACTs were measured using a Medtronic HemoTec ACT measurement system in samples obtained by intracardiac puncture from normal, nonanticoagulated, anesthetized rats and hamsters. Another groups of animals received different intravenous boluses of heparin to determine the dose needed to maintain ACT values > 480 sec for at least 30 min. The ACT (mean +/- SEM) was 48.0 +/- 2.17 sec for the 50 rats sampled and 42.5 +/- 2.35 sec for the 48 hamsters. Rats required a bolus of 1200 IU/kg intravenous heparin to maintain an ACT > 480 sec for 30 min; hamsters required 1000 IU/kg heparin for the same effect. We concluded that compared with humans, rats and hamsters from our colony have short ACTs and low sensitivity to heparin, in terms of the dose needed to reach a target ACT as well as the time required to sustain it. Further the ACT values in these animals showed great variability.

Comparative analysis of normal prion protein expression on human, rodent, and ruminant blood cells by using a panel of prion antibodies.

BACKGROUND: It is not known whether variant CJD can be transmitted within the human population by blood transfusion. The expression of normal cellular prion protein (PrPC) by different blood cell types may permit selective uptake and dissemination of infectivity. STUDY DESIGN AND METHODS: The normal distribution of PrPC on the major blood cell types of species known to be susceptible to natural or experimental transmissible spongiform encephalopathies was studied. Blood from healthy humans, mice, hamsters, cattle, and sheep was examined by flow cytometry by using a large panel of antibodies with different prion protein (PrP) epitope specificities to maximize the detection of PrP variants across species and cell type. RESULTS: PrP was detected on all major human blood cells types except eosinophils, but was not detected as ubiquitously or uniformly on major blood cell types of different animal species. CONCLUSION: Different animal species have unique patterns of expression of PrPC on blood cell types, with none equivalent to the human pattern. This needs to be considered when extrapolating from animal models of blood-borne transmissible spongiform encephalopathy infectivity, particularly in regard to the risk assessment of potential variant CJD spread within the human population. The relationship between PrP distribution and infectivity distribution in blood needs further investigation.

Daily rhythm in serum melatonin and leptin levels in the Syrian hamster (Mesocricetus auratus).

Melatonin is produced and secreted by the pineal gland in a rhythmic manner; circulating levels are high at night and low in the day. Leptin is a hormone secreted by adipocytes as a product of the obese gene and plays an important role in regulating body energy homeostasis and reproductive function in rodents and humans. The present study was conducted to examine daily fluctuations in serum levels of melatonin and leptin in Syrian hamster. We measured serum leptin and melatonin levels by ELISA in (a) intact and pinealectomized (pinx) male hamsters kept under long daylight conditions [14 h of light (14L)]; (b) intact and pinx hamsters under short daylight (10L); and (c) intact hamsters in constant light (24L). Blood samples were obtained every 2 h throughout a 24-h period. Statistically significant circadian variations were found in both melatonin and leptin profiles. Their relationship was inverse, i.e. when melatonin was high in the serum, leptin was comparably low. These results suggest that there is a rhythm in leptin levels in the adult male Syrian hamster and this rhythm is pineal gland (melatonin) and/or photoperiod dependent.

Immunisation with DNA encoding Leishmania infantum protein papLe22 decreases the frequency of parasitemic episodes in infected hamsters.

We tested in outbred golden hamsters the protective potential of highly immunogenic Leishmania infantum protein papLe22 which we recently identified. Immunisation was performed using papLe22 cDNA, administered as a single intramuscular injection. The level of antibodies directed against total leishmanial antigens was significantly decreased in the vaccinated hamsters as compared with the controls, indicating that the administration of papLe22 cDNA downregulated the Th2 type response and suggesting that the immune response was reoriented toward the cell-mediated type. The presence of the parasite kDNA in the peripheral blood was systematically detected as early as 3 weeks post infection in all mock-vaccinated hamsters. By contrast, in the vaccinated animals the occurrence of the episodes of Leishmania circulation was reduced by 50%. The immunisation presenting efficacy in this highly susceptible species which develop VL similar in gravity to human and canine disease should prove also efficient in naturally infected hosts. The marked decrease of the frequency of parasite circulation induced by papLe22 cDNA immunisation appears therefore important and potentially able to reduce transmission and thus to control the spread of the disease.

Immunomodulatory effects of pretransplant donor blood transfusion on T-cell-independent xenoreactive immunity.

BACKGROUND: Pretransplant blood transfusions have beneficial effects on both clinical and experimental allograft survival. In the present study, we examined whether pretransplant hamster blood transfusions (pHBT) alone or together with peritransfusion immunosuppressive strategies designed to target B cells and/or natural killer (NK) cells, could modulate T cell-independent (T-I) xenoreactivity in athymic nude rats. METHODS: Hamster or mouse hearts were heterotopically xenotransplanted into untreated or treated athymic nude rats receiving either pHBT, anti-B cell or anti-NK cell therapy alone or their combinations. Xenoreactive antibodies (xAbs) and the percentage of NK cells were analyzed by FACScan analysis. NK cytotoxicity was measured by a standard 4 hr 51Cr release assay. Xenografts (Xgs) were examined by hematoxylin-eosin (H&E), by light microscopic method with Masson's trichrome and orcein staining, by immunofluorescent staining for immunoglobulin M and C3 deposition, and by immunohistochemical staining for infiltration of NK cells and macrophages (Mphis). RESULTS: In 1 of 6 rats given pHBT alone 2 weeks before receiving hamster xenografts, Xg survival was prolonged to 55 days compared with 3.0+/-1.2 days in the other 5 animals and with 3.0+/-0.6 days in untreated animals. In the 55 days, surviving Xg infiltration of Mphis and NK cells was seen together with severe signs of chronic rejection, such as fibrosis and obliterative vasculopathy. The addition of the anti-B cell immunosuppressant MNA715 (malononitriloamide x920715, 20 mg/kg/day) from day -14 to day +14 or of 100 microL of rabbit anti-asialo GM1 serum ([anti-ASGM1] an NK cell depleting antibody) on day -14 resulted in a significant and species-specific prolongation of the survival of hamster Xgs, respectively 59.8+/-9.6 days and 58.2+/-14.7 days (P<0.001 vs. control group), but not of mouse heart Xgs that were rejected in a normal tempo. All prolonged hamster Xgs were infiltrated with Mphis and NK cells and developed severe lesions of chronic rejection, such as fibrosis and obliterative vasculopathy. In contrast, MNA715 or anti-ASGM1 alone had no effect on Xg survival (4.8+/-1.7 days and 2.7+/-0.6 days, respectively). Combined MNA715/anti-ASGM1 treatment only moderately promoted Xg survival (10+/-5.0 days; P<0.001). A simultaneous administration of pHBT, MNA715, and anti-ASGM1 induced indefinite and species-specific Xg survival in all recipients. In vivo and in vitro studies demonstrated that both T-I B cell and NK cell species-specific xenotolerance were achieved. CONCLUSIONS: Pretransplant blood transfusion may have a species-specific immunomodulatory effect on T-I xenoreactivity. This effect is further enhanced by a temporary co-administration of MNA715 or by a single injection of anti-ASGM1. A combination of pHBT, MNA715, and anti-ASGM1 induces species-specific T-I xenotolerance.

Effects of cholestyramine on hepatic cholesterol 7alpha-hydroxylase and serum 7alpha-hydroxycholesterol in the hamster.

Cholestyramine increases activities of hepatic cholesterol 7alpha-hydroxylase and serum levels of 7alpha-hydroxycholesterol. To examine if serum 7alpha-hydroxycholesterol levels parallel with enzyme activity, 0, 0.5, 1, 2, 4, and 10% of cholestyramine was administered to female golden Syrian hamsters for 28 d in the dose-dependent study, and 2% cholestyramine for 0, 1, 3, 7, 14, 21, and 28 d in the time-dependent study. In the dose-dependent study, hepatic and serum cholesterol levels were significantly decreased dose-dependently when more than 0.5% of cholestyramine was fed for 28 d. Cholestyramine increased the cholesterol 7alpha-hydroxylase activity in a dose-dependent manner, while the serum 7alpha-hydroxycholesterol level was essentially unchanged. No correlation was found between the serum level and the hepatic enzyme activity. In the time-dependent study, hepatic and serum cholesterol levels markedly decreased when 2% cholestyramine was fed for longer than 3 d. The serum triglyceride level increased significantly for the first 7 d and then decreased. Cholesterol 7alpha-hydroxylase activity increased significantly as early as day 1, reached maximum activity level on day 7, and then kept the significantly high values until day 28. The serum 7alpha-hydroxycholesterol level significantly increased for the first 7 d and decreased to the pretreatment level thereafter. 7Alpha-hydroxycholesterol levels significantly correlated with serum cholesterol and triglyceride levels. We conclude that the serum 7alpha-hydroxycholesterol level does not always reflect the activity of hepatic cholesterol 7alpha-hydroxylase, when cholesterol metabolism is severely disturbed by cholestyramine.

Hamsters and guinea pigs differ in their plasma lipoprotein cholesterol distribution when fed diets varying in animal protein, soluble fiber, or cholesterol content.

There were two objectives to these studies: 1) to compare the lipoprotein cholesterol distribution in two animal models in response to different dietary treatments and 2) to assess whether the hypercholesterolemia induced by high cholesterol intake could be reversed by consumption of vegetable-protein and/or dietary fiber. Guinea pigs, which carry the majority of plasma cholesterol in LDL, and hamsters, with a higher distribution of cholesterol in HDL, were evaluated in three different studies. In Study 1, animals were fed semi-purified diets for 4 wk with proportions of 60:40, 20:80 or 0:100 (w/w) of casein/ soybean protein. Hamsters and guinea pigs that consumed 100% soybean protein had lower plasma total cholesterol (TC) than those fed diets containing casein (P < 0.01). In Study 2, three doses of dietary pectin (2.7, 5.4, or 10.7 g/100g) added in place of cellulose were tested. Intake of 10.7 g/100 g pectin resulted in the lowest plasma TC concentrations for both species (P < 0.01). Although the TC lowering was similar in studies 1 and 2, the lipoprotein cholesterol distribution differed. Whereas the differences in plasma cholesterol were in LDL in guinea pigs, hamsters exhibited differences in both non-HDL and HDL cholesterol. In study 3, animals were fed 100% soybean protein, 10.7 g/100 g pectin, and three doses of dietary cholesterol: 0.04, 0.08, or 0.16 g/100 g, which is equivalent to 300, 600, or 1,200 mg/d in humans. Guinea pigs and hamsters had the highest plasma LDL and hepatic cholesterol concentrations when they consumed 0.16 g/100 g of cholesterol (P < 0.01). However, intake of 0.08 g/100 g of cholesterol resulted in lower plasma LDL cholesterol concentrations than did consuming high animal protein (60:40 casein/ soy) or low soluble fiber (2.7 g/100 g). Relatively high levels of dietary cholesterol combined with vegetable protein and soluble fiber resulted in desirable lipoprotein profiles in animal models that significantly differ in their lipoprotein cholesterol distribution.

Effects of immobilization restraint on Syrian golden hamsters.

Rodent nose-only inhalation toxicology systems comprise whole-body immobilization in plastic restraint tubes. This method of restraint is known to have a variety of effects on animals. In the studies reported here, two independent toxicology laboratories examined the effects of inhalation tube restraint in Syrian golden hamsters, a species that has recently gained importance in inhalation studies of fibrous particulates. Body weight, food and water consumption, core body temperature, and plasma cortisol and corticosterone concentrations were assessed in animals immobilized in nose-only inhalation tubes, and the results were compared with those from unrestrained cage-control animals. Animals were immobilized for either 6 h/ day, 5 days/week for 13 weeks (subchronic), or 4 h/day for 14 consecutive days (subacute), mimicking exposure conditions commonly used in nose-only inhalation studies. Tube restraint was found to induce a marked decrease in body weight, which increased in response to cessation of restraint. The body weight decrement was associated with significant differences in food and water consumption between the restrained and control groups in the subacute study and only food consumption in the subchronic study. During the restraint period, core body temperature in the immobilized animals increased slightly but not above the normal range for this species. Plasma cortisol and corticosterone concentrations were not significantly increased with use of restraint, compared with values in controls. Immobilization-associated body weight depression in Syrian golden hamsters is important for the evaluation of nose-only inhalation study results because many normal physiologic parameters, as well as toxicant-induced effects, are associated with body weight status.