Hamsters Research Articles

Isolation and characterization of myotubes from bio 14.6 hamsters

Isolation and characterization of myotubes from bio 14.6 hamsters

Auditory deprivation modifies biological rhythms in the golden hamster.

To assess to what extent auditory sensory deprivation affects biological rhythmicity, sleep/wakefulness cycle and 24 h rhythm in locomotor activity were examined in golden hamsters after bilateral cochlear lesion. An increase in total sleep time as well as a decrease in wakefulness (W) were associated to an augmented number of W episodes, as well as of slow wave sleep (SWS) and paradoxical sleep (PS) episodes in deaf hamsters. The number of episodes of the three behavioural states and the percent duration of W and SWS increased significantly during the light phase of daily photoperiod only. Lower amplitudes of locomotor activity rhythm and a different phase angle as far as light off were found in deaf hamsters kept either under light-dark photoperiod or in constant darkness. Period of locomotor activity remained unchanged after cochlear lesions. The results indicate that auditory deprivation disturbs photic synchronization of rhythms with little effect on the clock timing mechanism itself.

Effect of ovarian stimulation with or without GnRH agonist on hamster endometrial secretion

The present study was undertaken to evaluate the endometrial secretion and synthesis of proteins in hamsters that were subjected to ovarian stimulation with or without GnRH agonist (Leuprolide Acetate, LA). The results of protein resolution revealed that the molecular weight of the proteins increased from 31D to 66D, while the intensities of photographed protein bands in the hamsters treated with LA and pregnant mare’ s serum gonadotropin (PMSG) were less than that in those treated with PMSG alone. The amounts of low and medium weights (31kD and 45kD) proteins newly synthesized in LA+PMSG group and saline group (control) were significantly higher than that in PMSG group. The synthesized and secreted proteins in groups LA and control were similar. The data suggested that a physiologic endometrial protein secretory and synthetic change with GnRH agonist regarcded as a possible cause of the higher pregnancy rate in in vitro fertilization. The degree of endometrial secretion and synthesis varied considerably with the type of ovarian stimulation used.

Modulation of cytochrome P450-dependent monooxygenases in streptozotocin-induced diabetic hamster: II. Reverse role of insulin in P450 activity and defluorination.

Metabolic activities of cytochrome (cyt) P450-dependent monooxygenase could be modulated by diabetic state in experimental diabetic animals. The purpose of this study is to validate the effect of insulin on the modulation of the metabolic activity of cyt P450 and the defluorination ability to inhalational anesthetics in diabetic animals. Diabetic state in golden Syrian hamsters was achieved by intraperitoneal injection of streptozotocin 40 mg/kg once a day for 4 days. After stabilization of diabetic state for 6 weeks, a regimen of insulin treatment given subcutaneously was carried out. Metabolic activities of cyt P450 were assessed by the reaction with benzo(a) pyrene, pentoxyresorufin, aniline and erythromycin (specific substrates). The metabolic activities of cyt 1A1, 2B1, 2E1 and 3A4 respectively in a NADPH-generating system in microsomal preparations of the diabetic hamsters were observed before and after insulin treatment, and were compared with the control group. The ability of defluorination was evaluated by measuring the free fluoride metabolites after incubating the microsomes with enflurane in diabetic and insulin-treated hamsters. Contents of cyt P450 isozymes were measured by electrophoresis and immunoblotting before and after insulin treatment. Pathological features of hepatocytes in diabetic hamsters were evaluated microscopically before and after insulin treatment. The defluorination of enflurane and activity of aniline hydroxylase (cyt 2E1) were successfully induced by diabetic state (P < 0.01). The pentoxyresorufin O-dealkylase (cyt 2B1) was inhibited nearly 50% in the diabetic hamster liver when compared with that of control (P < 0.01). While the activities of benzo(a)pyrene hydroxylase (cyt 1A1) and the erythromycin N-demethylase (cyt 3A4) were basically unaffected by diabetes, alterations in content of cyt P450 were parallel to the alterations in enzyme activities. Microscopically, diabetes induced vacuolization with fatty droplets in the hepatocytes. After treatment with insulin injection, the enzyme activities, protein content and pathologic features returned to the baseline similar to the control. Our data demonstrated that under diabetic state, metabolic activities of cyt P450 and its extent of defluorination would be polymorphically modulated. After administration of insulin, the activities of cyt P450 and defluorination of enflurane returned to baseline as the blood sugar level had been normalized. This could remind the clinicians of the importance of insulin treatment in the potential drug-to-drug interactions in the diabetic patients.

DISTURBANCES OF ACID-BASE BALANCE FOLLOWING DISCORDANT GUINEA PIG??? RAT LIVER XENOTRANSPLANTATION

190 The physiological incongruity that may be associated with orthotopically transplanted livers across discordant but not concordant species is being widely debated. Of primary concern is the different methods employed by various species for bile secretion. While in both rats and hamsters (HAM) this phenomenon is bile acid-dependent; in guinea pigs (GP) on the contrary, it is driven largely by osmosis established by a HCO3- concentration gradient. Additionally, bile flow is also appreciably higher (×4) in GP as compared to that in rats. In the light of heretofore raised arguments, we proceeded to ascertain the effect of these anomalies on the HCO3- and pH of rat recipients of GP livers (Group VI). Recipients of liver transplantation (LTX) across syngeneic (syn; Group IV) and concordant (con; HAM→ rat; Group V) strain combinations were used as controls. Recipients in Group IV, V and VI received cobra venom factor (80µg/kg) on d-1 as well as tacrolimus (1mg/kg/d) and CellCept (10mg/kg/d) from d-1 onwards. Arterial blood samples were collected on d1 and 2 post-Tx for analysis, the results are as follows: While the use of immunosuppression completely prevented the rejection of xenografts in Group V animals, it failed to prolong survival in Group VI recipients beyond d3 post-Tx. However, for the first two post-operative days except for slight hyperventilation, animals in Group VI were active and with normal behavior. As is depicted in the table, blood pH, pCO2 and HCO3- levels remained stable in animals in Group IV and V. However within 24 hours post-Tx, the HCO3- levels in Group VI animals were significantly reduced with an accompanying decrease in pH. Additionally, respiratory compensation in these recipients also markedly reduced the pCO2 levels. While, HCO3- levels in the bile of naive rats and HAM were found to be similar (37.1±2.7 and 31.6±3.6 mmol/L, respectively), they were nevertheless, 3× higher (103.8±5.0 mmol/L) in the bile of GP. This phenotype was preserved in Group VI recipients where bile HCO3- levels increased 3-fold to around 100 mmol/L on dl and 2 post-Tx. In conclusion, the higher concentration of HCO3- in the bile of GP livers along with a higher flow rate results in rapid loss of HCO3- buffer from the plasma of GP→ rat liver transplant recipients who exhibit a propensity towards developing metabolic acidosis. Immunological discordancy should not be viewed as a separate entity, for it is coupled with physiological and metabolic incompatibilities observed especially after Tx of a multifunctional organ such as a liver across genetically disparate species.Table

Sperm motion predicts fertility in male hamsters treated with alpha-chlorohydrin.

An understanding of the relationship between altered sperm motion and sperm function (fertility) is important when interpreting the biological significance of toxicant-induced changes in sperm velocity in rodent test species. Previous studies showed that a brief (4-day) exposure of male hamsters to the model chemical alpha-chlorohydrin (ACH) results in significant deficits in epididymal and uterine sperm velocity, which are associated with both a delay and a failure of fertilization in vivo. To characterize this effect in terms of fertility, similarly treated male hamsters were bred to untreated females and pups were counted the day before parturition. ACH treatment resulted in a dose-dependent decline in the percentage of sperm-positive females that were pregnant at the end of gestation (100, 78, 67, 22, and 0 where males were treated with 0, 33, 49, 66, and 83 mg ACH/kg/day, respectively). Cauda epididymal sperm from the same males were assayed for motion characteristics using computer-assisted sperm analysis (CASA), and for fertilizing ability in vitro. While the percentage of motile sperm was unaffected by ACH treatment, sperm velocity declined in a dose-dependent manner at all ACH treatment levels. Furthermore, the velocity of sperm from infertile males was shifted downward consistently across the entire velocity distribution. Since treated males tended to either be infertile (no pups) or have near normal litter size, the correlation between sperm velocity and litter size was nonlinear. Therefore, logistic regression models using velocity cut-off values were the most useful models for predicting fertility. These results support the contention that fertility relies on there being a sufficient number of sperm that exceed a velocity threshold. Sperm from treated males were also less likely to support in vitro fertilization (IVF), providing further evidence of impaired sperm function associated with acute exposure to ACH.

Identification and partial characterization of a myosin-like protein from cysticerci and adults of Taenia solium using a monoclonal antibody.

The host-parasite relationship in taeniosis due to Taenia solium is practically unknown. Monoclonal antibodies were prepared against whole extracts of adult T. solium parasites and evaluated with tapeworms recovered from experimentally infected hamsters and with cysticerci from naturally infected pigs. With one antibody, mAb 4B3, it was possible to identify, purify and partially characterize a T. solium myosin. Some findings indicate that it corresponds to conventional myosin or myosin type II such as: purification with KCl, high molecular weight, size, structure (dimeric protein with globular and long tail portions), reaction with commercial anti-myosin antibodies, distribution in muscle fibres of parasites and cross-reactivity with antibodies against paramyosin from T. solium cysticerci. The reaction of the mAb was only with taeniids and not with other parasites. Also myosin was detected in faeces of infected animals and in supernatants of parasite cultures. Its presence in biological fluids may be useful for diagnosis of infected hosts.

DEXAMETHASONE PROTECTS HAMSTERS FROM FIBROSIS BUT NOT INFLAMMATION INDUCED BY INTRATRACHEAL AMIODARONE

The antiarrhythmic drug amiodarone (AD) m ay cause severe lung damage in human patients. Often these patients are treated with corticosteroids; the usefulness of steroids in alleviating AD-induced lung disease has never been adequately studied, however. Intratracheal instillation of AD to hamsters causes pulmonary inflammation and fibrosis. The objective of this study was to examine whether corticosteroid treatment protects hamsters from AD-induced pulm onary inflammation and fibrosis. Male Syrian ham sters were treated with dexamethasone or saline and then instilled with AD or saline. Dexam ethasone treatm ent blocked the AD-induced increase in lung hydroxyproline content, an index of fibrosis. Analysis of bronchoalveolar lavage fluid showed that dexamethasone partially blocked AD-induced increases in total cells, m acrophages, and eosinophils. Dexam ethasone did not protect against the increase in neutrophils associated with AD treatm ent; neutrophil influx is widely utilized as a marker of inflamm ation. Dexam ethasone also failed to block the increase in lavage fluid albumin resulting from AD treatment; albumin in lavage fluid is considered an index of alveolar-capillary permeability. This study demonstrates that dexamethasone prevents AD-induced pulmonary fibrosis in hamsters while having m inim al effects on inflam mation.

Two distinct retinal projections to the hamster suprachiasmatic nucleus.

Electrical stimulation of the intergeniculate leaflet (IGL) region in hamsters can induce expression of Fos-like immunoreactivity (lir) in a restricted portion of the dorsolateral suprachiasmatic nucleus (SCN). The authors investigated whether the mechanisms by which stimulation affects SCN cells involves orthodromic activation of IGL cells projecting to the SCN or antidromic activation of retinal ganglion cells that send bifurcating axonal projections to both the IGL and the SCN. Bilateral optic enucleation strongly reduced induction of Fos-lir in SCN cells in response to electrical stimulation of the IGL region, implicating antidromic activation of retinal ganglion cells as the mechanism. This result implies that a class of retinal ganglion cells that project to the IGL also project selectively to the dorsolateral SCN. Earlier pharmacological studies suggest that this anatomically distinct retinal projection to the SCN is also neurochemically different from that innervating the rest of the nucleus.

Synchronous assessment of sperm motility and fertilizing ability in the hamster following treatment with alpha-chlorohydrin.

To investigate the relationship between sperm motion parameters and fertilizing ability, a model was developed to assess both of these endpoints synchronously using a toxicant that inhibits sperm motion. alpha-Chlorohydrin (ACH) was administered daily for 4 days to male hamsters at 0, 33, 49, 66, and 83 mg/kg body weight. These males were then allowed a 45-minute breeding period with untreated estrus females on the morning of day 5. One hour after breeding, sperm samples were surgically recovered from the uteri of the females for motility analysis. Six hours later, eggs were flushed from the oviducts and evaluated for fertilization. Cauda epididymal sperm were also collected from the males shortly after breeding. Proportions of motile and progressively motile sperm were manually quantified, and overall sperm velocity and the velocity of representative vigorously swimming sperm in both the uterine and epididymal samples were measured by computer-aided sperm analysis. Significant decreases in in vivo fertilization rates and epididymal sperm motion parameters were observed at 66 and 83 mg/kg ACH, whereas uterine sperm motion was adversely affected at all ACH dosages used. All sperm motion parameters except the percentage of motile sperm in the epididymis were significantly correlated with fertilization rates by both linear and logistic regression. Overall, uterine and epididymal sperm endpoints predicted fertilizing ability comparably well. Stepwise multiple linear regression gave a model containing epididymal sperm velocity (EVCL) and uterine sperm percent motility (UMOT) with an R2 value of 0.649. Stepwise multiple logistic regression gave models containing EVCL alone and EVCL and UMOT in binary (fertile/infertile) and quantal models, respectively.

CP-148,623 reverses pre-established hypercholesterolemia in hamsters

CP-148,623 reverses pre-established hypercholesterolemia in hamsters

Hamsters?? drinking problems controlled by ancient Chinese cure

Hamsters?? drinking problems controlled by ancient Chinese cure

Viscosity and fermentability as attributes of dietary fiber responsible for the hypocholesterolemic effect in hamsters.

The attribute(s) of soluble dietary fibers responsible for cholesterol lowering is currently uncertain. A series of experiments were conducted in which viscosity and fermentability was assessed independently for their effect on plasma and liver cholesterol concentration. Hamsters were divided into four dietary groups and fed diets containing 0.12% cholesterol and 5% fiber as high viscosity hydroxypropyl methylcellulose (HV-HPMC group), low viscosity hydroxypropyl methylcellulose (LV-HPMC group), high viscosity guar gum (HV-GG group) or low viscosity guar gum (LV-GG group). Hydroxypropyl methylcellulose is essentially nonfermentable, whereas guar gum is highly fermentable. Plasma cholesterol concentrations at 3, 6 and 11 wk and liver cholesterol concentrations at 6 and 11 wk were significantly lower in the HV-HPMC group relative to the LV-HPMC group (P < 0.05). Intestinal content viscosities of the LV-HPMC and HV-GG groups were similar; consequently, these two groups were compared to examine the independent effect of fermentation. Plasma and liver cholesterol were significantly lower in the HV-GG group compared with the LV-HPMC group at 6 wk (P < 0.05), but not at 3 or 11 wk. Hepatic sterol synthesis rates were not affected by any of the diets. This study shows that greater viscosity of intestinal contents is strongly associated with cholesterol reduction, but that the contribution of fiber fermentation remains uncertain.

Characteristics of cadmium-induced nephrotoxicity in Syrian hamsters.

Male Syrian hamsters were used to evaluate cadmium (Cd)-induced nephrotoxicity. Furthermore, they were treated with polyaspartic acid (PAA) in an attempt to prevent renal damage due to Cd. To induce renal proximal tubular damage, the hamsters were administered a single subcutaneous injection of cadmium chloride (CdCl2) at the dose of 3 mg/kg body weight. Within 24 hours, they exhibited significant proteinuria and an increased urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG). Renal histological changes consisted of degenerative changes in renal tubule cells, irregularly shaped nuclei with marginated chromatin and rounded mitochondria. The administration of PAA did not improve creatinine clearance or urinary protein excretion. The concentration of Cd in the renal tissue showed a gradual increase on day 3 following cadmium exposure. Cadmium nephrotoxicity appears to be more severe in Syrian hamsters than in rats or mice. Thus, this animal model appears to be excellent for studying Cd-induced nephrotoxicity.

Pituitary-testicular axis in cardiomyopathic Syrian hamsters.

Testicular function and other endocrine parameters were studied in cardiomyopathic hamsters. In these animals, the major defect is an intracellular calcium overload, which is due to defective voltage-sensitive calcium channels. Basal circulating gonadotropin, prolactin, and triiodothyronine levels were lower in cardiomyopathic hamsters than in normal hamsters, but thyroxine, progesterone, and testosterone levels were not. In cardiomyopathic hamsters, the luteinizing hormone receptor (LHR) positive autoregulation by human chorionic gonadotropin (hCG) reached a maximum faster and at a lower dose than in normal hamsters. Similar results were observed for the response of circulating testosterone to hCG administration. The data indicate that, in spite of deficient pituitary function, cardiomyopathic hamsters have a normal or more efficient testicular function. This is probably the result of the cellular calcium overload, which would stimulate Leydig cell gene transcription, specifically that for LHR.

Experimental studies on the late effects of female sex hormones.

Inj. Hydroxyprogesterone Co. (EP) was injected i.m. into female Wistar rats, different strains of mice of both sex and Syrian golden hamsters with doses of 5-100 times the human contraceptive dose once or twice a month for 10-32 times. In some experiments EP was combined with whole-body 3 Gy gamma ray radiation once or twice. Results show that EP has obvious carcinogenicity and can enhance the gamma ray carcinogenicity, thereby increasing the tumor incidence or the ratio of malignant to benign tumours. Carcinogenic mechanisms of EP have also been studied.

Toxicity and Metabolism of Trimethylarsine in Mice and Hamsters

Toxicity and Metabolism of Trimethylarsine in Mice and Hamsters

Tubulovesicular structures in experimental Creutzfeldt-Jakob disease and scrapie.

Tubulovesicular structures, measuring 20-50 nm in diameter, were found in dilated neuronal processes in brains from mice infected with the Fujisaki strain of Creutzfeldt-Jakob disease virus. These particles were similar to those observed in brains from hamsters infected with scrapie. These structures are consistently present in naturally occurring and experimentally induced spongiform encephalopathies, irrespective of the host species or virus strain. Their role in pathogenesis is undetermined.

Analysis of Tastes in Mixtures by Hamstersa

Analysis of Tastes in Mixtures by Hamsters^a

Production of a growth factor(s) by fibroblasts from the lungs of ventilated premature baboons and oxygen-exposed adult hamsters.

Among the pathologic findings in infants succumbing to bronchopulmonary dysplasia are peribronchiolar and alveolar fibrosis. We examined the possibility that endogenously produced growth factors might contribute to these fibrotic changes through stimulation of fibroblast replication, with a resulting increase in collagen synthesis. We cultured fibroblasts from the lungs of prematurely delivered baboons and adult hamsters exposed to 100% oxygen and tested the media from these cells to see if they produced a factor(s) that was mitogenic to normal fibroblasts. We found that lung fibroblasts from baboons delivered prematurely at 140 days of gestation and ventilated for 6 days with 100% oxygen produced a factor(s) that supported fibroblast growth. A similar factor was also secreted by fibroblasts from normal term newborn baboon lungs and from the lungs of adult hamsters exposed to 100% oxygen for 4 to 8 days. Growth factor was not secreted by lung fibroblasts from 140-day non-breathing or 24-h-ventilated premature baboons, adult baboons, or hamsters not exposed oxygen. The growth-promoting substance is apparently a progression factor that is heat labile and inactivated by exposure to trypsin. These findings indicate that exposure of both the premature and adult lung to high concentrations of oxygen causes the elaboration of a growth factor that may induce fibroblast hyperplasia. This action may result in an increased production of connective tissue proteins and thereby contribute to the development of the fibrosis seen in bronchopulmonary dysplasia.