Recombinant Measles Virus Vaccine Expressing the Nipah Virus Glycoprotein Protects against Lethal Nipah Virus Challenge

Nipah virus (NiV) is a member of the genus Henipavirus, which emerged in Malaysia in 1998. In pigs, infection resulted in a predominantly non-lethal respiratory disease; however, infection in humans resulted in over 100 deaths. Nipah virus has continued to re-emerge in Bangladesh and India, and person-to-person transmission appeared in the outbreak. Although a number of NiV vaccine studies have been reported, there are currently no vaccines or treatments licensed for human use. In this study, we have developed a recombinant measles virus (rMV) vaccine expressing NiV envelope glycoproteins (rMV-HL-G and rMV-Ed-G). Vaccinated hamsters were completely protected against NiV challenge, while the mortality of unvaccinated control hamsters was 90%. We trialed our vaccine in a non-human primate model, African green monkeys. Upon intraperitoneal infection with NiV, monkeys showed several clinical signs of disease including severe depression, reduced ability to move and decreased food ingestion and died at 7 days post infection (dpi). Intranasal and oral inoculation induced similar clinical illness in monkeys, evident around 9 dpi, and resulted in a moribund stage around 14 dpi. Two monkeys immunized subcutaneously with rMV-Ed-G showed no clinical illness prior to euthanasia after challenge with NiV. Viral RNA was not detected in any organ samples collected from vaccinated monkeys, and no pathological changes were found upon histopathological examination. From our findings, we propose that rMV-NiV-G is an appropriate NiV vaccine candidate for use in humans.     

Beneficial effects of cardiac chymase inhibition during the acute phase of myocardial infarction

Recently, the presence of the chymase-dependent angiotensin (Ang) II-generating system in hamsters, dogs, monkeys, as well as human cardiovascular tissues has been identified. We have reported that the activation of cardiac chymase was more prominent than that of angiotensin converting enzyme (ACE) and that AT1 receptor antagonist treatment rather than ACE inhibitor treatment alone provided significant beneficial effects on cardiac function and survival after MI in hamsters. The aim of the present study was to determine whether this different effects between AT1 receptor antagonist and ACE inhibitor were due to the activation of cardiac chymase after MI in hamsters by using 4-[1-[[bis-(4-methyl-pheny)-methyl]-carbamoyl]-3-(2-ethoxy-benzyl)-4-oxo-azetidine-2-yloxy]-benzoic acid (BCEAB), a novel, orally active and specific chymase inhibitor. The ACE and chymase activities in the infarcted left ventricle were significantly increased 3 days after MI. BCEAB (100 mg/kg/day, p.o.) treatment starting 3 days before MI significantly suppressed the cardiac chymase activity, while it did not affect the plasma and cardiac ACE activities 3 days after MI. A significant improvement in hemodynamics (maximal negative and positive rates of pressure development; left ventricular systolic pressure) was observed for the treatment with BCEAB 3 days after MI. BCEAB (100 mg/kg/day, p.o.) treatment starting 3 days before MI significantly reduced the mortality rate during 14 days of observation following MI (vehicle, 61.1%, n = 18; BCEAB, 27.8%, n = 18; P < 0.05). These findings demonstrated for the first time that cardiac chymase participates directly in the pathophysiologic state after MI in hamsters.     

The mutagenic activity of aflatoxin B1 in the Cricetulus griseus hamster and Macaca mulatta monkey

Chromosome aberrations were scored in bone marrow cells of Cricetulus griseus hamsters and Macaca mulatta monkeys given a single i.p. injection of aflatoxin B1 (AFB1). The mutagenic activity of AFB1 was assessed by the percentage of cells bearing aberrations and by the total frequency of chromosome and chromatid breaks. Chinese hamsters were treated with five different doses of AFB1 ranging from 1 microgram to 5 mg/kg (LD50/30 = 12.2 mg/kg) and the aberration yields at each AFB1 dose level tested were determined at 24 h intervals for 5 consecutive days. Compared to controls the increase in the two types of chromosome abnormalities was significant in all tests. At 5 mg/kg of AFB1 the tests were carried out over a period of 92 days to assure the analysis of aberration yields with time. All chromosome aberration assays conducted during this period showed significant increases in the frequencies of aberrant cells and chromosome and chromatid breaks in comparison to controls. Macaque monkeys were treated in the same fashion using 0.1 and 1.0 mg/kg of AFB1 and the dynamics of chromosome aberration yields was analyzed for a period of 730 days. Similarly as in the case of Chinese hamsters the percentage of cells with aberrations and the frequency of chromosome and chromatid breaks were always higher in this period than the control value. Long-term aberration yield data obtained experimentally were expressed in the form of analytical curves which allowed to establish the time when the yields of aberrant cells reached their maxima and when they returned to the control level. In both animal species tested the courses of analytical curves had a similar dynamics. Factors that might be responsible for a long-term persistence and relatively great fluctuations of the chromosome aberration yields encountered after a single injection of AFB1 are discussed in detail.     

Inhaled radon-induced genotoxicity in Wistar rat,Syrian hamster,and Chinese hamster deep-lung fibroblasts in vivo

This study was performed (1) to provide a comparison of the genotoxin effects of inhaled radon and radon progeny, referred to as radon in this paper, among three species of rodents: Wistar rats, Syrian hamsters, and Chinese hamsters; (2) to determine if initial chromosome damage was related to the risk of induction of lung cancer; and (3) to evaluate the tissue repair and long-term presence of cytogenetic damage in respiratory tract cells. These species were selected because Syrian hamsters are very resistant to radon induction of lung cancer and Wistar rats are sensitive; no literature is available on the in vivo effects of radon in the Chinese hamster. Exposure-response relationships were established for the rats and Syrian hamsters while the Chinese hamsters received a single exposure of radon. At 4 h (0.2 days), 15 days, and 30 days after the highest WLM exposure to radon, Wistar rats, Chinese hamsters, and Syrian hamsters were killed, and lung fibroblasts were isolated and grown in culture to determine the frequency of induced micronuclei. Animals at each level of exposure showed an increase in the frequency of micronuclei relative to that in controls (P < 0.05). The exposure-response relationship data for rats and Syrian hamsters killed 0.2 days after the end of exposure were fit to linear equations (micronuclei/1000 binucleated cells = 15.5±14.4+0.53±0.06 WLM and 38.3±15.1+0.80±0.08 WLM, respectively). For the single exposure level used (496 WLM) in Chinese hamsters killed at 0.2 days after exposure, the frequency of micronuclei/1000 binucleated cells/WLM was 1.83±0.02. A comparison of the sensitivity for induction of micronuclei/WLM illustrated that Chinese hamsters were three times more sensitive than rats. The Syrian hamsters also showed a significantly elevated response (P < 0.05) relative to rats. These data suggest that initial chromosome damage is not the major factor responsible for the high rate of radon-induced cancer in rats relative to Syrian hamsters. The frequency of micronuclei in radon-exposed rats, Syrian hamsters, and Chinese hamsters significantly decreased (P < 0.05) as a function of time after the exposure. The rate of loss of damaged cells from the lung was greatest in the Chinese hamsters, followed by Wistar rats and Syrian hamsters, respectively. Our experiments demonstrated that the mammalian lung fibroblast/micronucleus method has the potential to (1) detect species differences in the induction of in vivo genotoxic damage in the lungs by inhaled environmentalal agents; (2) evaluate exposure-response relationships for in vivo induction of genetic damage; and (3) determine the persistence in vivo of preclastogenic and premutagenic lesions in cell populations.     

Timing of testicular recrudescence in siberian hamsters is unaffected by pinealectomy or long-day photoperiod after 9 weeks in short days

In this study, the authors asked whether pinealectomy or temporary exposure to a stimulatory photoperiod affects the timing of spontaneous testicular recrudescence in adult Siberian hamsters chronically exposed to short days (9:15 light:dark). In Experiment 1, hamsters were pinealectomized after 6, 9, or 12 weeks in short days. Pinealectomy after 9 or 12 weeks did not affect the timing of spontaneous gonadal growth (27.7 +/- 1.9 and 25.4 +/- 1.3 weeks, respectively) compared to sham-operated controls (28.6 +/- 0.9 weeks). Enlarged testes occurred earlier in animals that were pinealectomized after 6 weeks in short days (21.8 +/- 2.1 weeks). In Experiment 2, adult hamsters were exposed to short days for 9 weeks, transferred to long days (16:8 light:dark) for 4 weeks, and then returned to short days for 23 additional weeks. Although long-day interruption caused gonadal growth in 15 out of 19 hamsters, the temporary long-day exposure did not affect the timing of spontaneous gonadal growth following return to short days (28.2 +/- 0.9 weeks) in 10 of the 15, relative to the timing observed in control hamsters continuously maintained in short days (28.2 +/- 1.1 weeks). Four out of 19 hamsters did not show gonadal growth following long-day exposure. Spontaneous gonadal growth in these hamsters (28.0 +/- 1.4 weeks) also occurred at the same time as controls. The remaining 5 hamsters exhibited enlarged testes following long-day exposure (12.0 +/- 0.0 weeks) but were refractory to the second short-day exposure. All hamsters exhibited entrainment of wheel-running activity following the change in photoperiod. A final group of 13 animals were pinealectomized before long-day transfer. They exhibited gonadal growth (at 17.2 +/- 0.8 weeks) but failed to regress a second time when returned to short days. The timing of gonadal growth in these animals was delayed relative to the sham-operated hamsters temporarily transferred to long days (Experiment 2) but accelerated relative to the hamsters pinealectomized at 9 weeks, which remained continuously in short days (Experiment 1). The results of both experiments suggest that a pineal-independent process mediates the timing of spontaneous gonadal growth in Siberian hamsters chronically exposed to a short-day photoperiod.     

Architecture of the dorsal and ventral lobes of the prostate of the Syrian hamster, Mesocricetus auratus, after regrowth from short day-induced regression

The structures of the dorsal and ventral lobes of the prostate of 4 groups of Syrian hamsters were studied by a stereological approach. Groups studied were young hamsters (kept in long-day photoperiods for 4 weeks) in their first breeding season, older hamsters (kept in short-day photoperiods for 24 weeks so that their prostates had regressed and regrown) in their second breeding season, and two groups of older hamsters in an extended first breeding season (either because they were kept in long days for 24 weeks or because they were pinealectomized before being put into short-day photoperiods for 24 weeks). There were very few differences between groups, but generally dorsal prostates of older hamsters in their second breeding season closely resembled those of young hamsters in their first breeding season. More differences were noted between either of these two groups and older hamsters in an extended first breeding season than between these two groups. The differences noted generally involved increases in the amount of smooth muscle in the walls of secretory tubules in the dorsal prostates of hamsters in an extended first breeding season. This may be associated with the fact that these glands had not regressed and regrown. Ventral prostates were very similar in all 4 groups, which may reflect the fact that they normally regress very little in short days.     

Active and passive vaccination against hantavirus pulmonary syndrome with Andes virus M genome segment-based DNA vaccine

Hantavirus pulmonary syndrome (HPS) is a rapidly progressing human disease with one of the highest case fatality rates (30 to 50%) of any acute viral disease known. There are no vaccines, effective antiviral drugs, or immunologics to prevent or treat HPS. In an attempt to develop HPS medical countermeasures, we constructed an expression plasmid, pWRG/AND-M, that contains the full-length M genome segment of Andes virus (ANDV), a South American hantavirus. Transfection experiments in cell culture indicated that both the G1 and G2 glycoproteins are expressed from pWRG/AND-M. Rhesus macaques vaccinated by gene gun with pWRG/AND-M developed remarkably high levels of neutralizing antibodies that not only neutralized ANDV but also cross-neutralized other HPS-associated hantaviruses, including Sin Nombre virus. To determine if the antibodies elicited in the monkeys could confer protection, we performed a series of passive-transfer experiments using a recently described lethal HPS animal model (i.e., adult Syrian hamsters develop HPS and die within 10 to 15 days after challenge with ANDV). When injected into hamsters 1 day before challenge, sera from the vaccinated monkeys either provided sterile protection or delayed the onset of HPS and death. When injected on day 4 or 5 after challenge, the monkey sera protected 100% of the hamsters from lethal disease. These data provide a proof of concept for a gene-based HPS vaccine and also demonstrate the potential value of a postexposure immunoprophylactic to treat individuals after exposure, or potential exposure, to these highly lethal hantaviruses.     

DNA vaccination with the Hantaan virus M gene protects Hamsters against three of four HFRS hantaviruses and elicits a high-titer neutralizing antibody response in Rhesus monkeys

Four hantaviruses-Hantaan virus (HTNV), Seoul virus (SEOV), Dobrava virus (DOBV) and Puumala virus-are known to cause hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia. HTNV causes the most severe form of HFRS (5 to 15% case-fatality rate) and afflicts tens of thousands of people annually. Previously, we demonstrated that DNA vaccination with a plasmid expressing the SEOV M gene elicited neutralizing antibodies and protected hamsters against infection with SEOV and HTNV. Here, we report the construction and evaluation of a DNA vaccine that expresses the HTNV M gene products, G1 and G2. DNA vaccination of hamsters with the HTNV M gene conferred sterile protection against infection with HTNV, SEOV, and DOBV. DNA vaccination of rhesus monkeys with either the SEOV or HTNV M gene elicited high levels of neutralizing antibodies. These are the first immunogenicity data for hantavirus DNA vaccines in nonhuman primates. Because a neutralizing antibody response is considered a surrogate marker for protective immunity in humans, our protection data in hamsters combined with the immunogenicity data in monkeys suggest that hantavirus M gene-based DNA vaccines could protect humans against the most severe forms of HFRS.     

Activity of quinfamide against natural infections of Entamoeba criceti in hamsters: a new potent agent for intestinal amoebiasis

A novel tetrahydroquinolinyl ester, quinfamide, administered orally in multiple doses for 3 days had an ED50 of 0.25 mg/kg/day (total dose 0.75 mg/kg) for eradicating Entamoeba criceti in hamsters in several tests. It was significantly more active by direct comparison than 3 commercially available amoebicides and at least as active as 2 other esters of the parent compound, 1-(dichloroacety)-1,2,3,4-tetrahydro-6-quinolinol. After administration of a single dose, ED50 calculations for quinfamide averaged 0.9 mg/kg. Quinfamide was considerably more active than the other tetrahydroquinolinols, diloxanide furoate and teclozan, and it was approximately 1.5 times more active than etofamide; a statistical significance between the latter 2 drugs could be demonstrated in one of 4 tests. Administered prophylactically, quinfamide was shown to protect hamsters from re-infection with E. criceti. It also inhibited propagation of E. histolytica in vitro at a concentration of 20 microgram/ml. No adverse effects were noted in rodents after a single dose as high as 10 g/kg. Daily administration to monkeys of doses up to 500 mg/kg for as long as 37 days produced no pharmacological aberrations during or after medication; haematological studies and urine analyses were normal and no gross or microscopical tissue changes attributable to quinfamide were observed. No toxicity was revealed following acute (2 g/kg) and chronic (500 mg/kg/day x 31 days) administration of the drug to dogs and rats, respectively.     

Use of ATP to characterize biomass viability in freely suspended and immobilized cell bioreactors

This work describes investigations into the viability of cells growing on 3,4-dichloroaniline (34DCA). Two bioreactors are employed for microbial growth, a continuous stirred tank (CST) bioreactor with a 2-L working volume, and a three-phase air lift (TPAL) bioreactor with a 3-L working volume. Experiments have been performed at several dilution rates between 0.027 and 0.115 h(-1) in the CST bioreactor and between 0.111 and 0.500 h(-1) in the TPAL bioreactor. The specific ATP concentration was calculated at each dilution rate in the suspended biomass in both bioreactors as well as in the immobilized biomass in the TPAL bioreactor. The ATP was extracted from the cells using boiling tris-EDTA buffer (pH 7.75), and the quantity determined using a firefly (bioluminescence) technique. The cultures were inspected under an electron microscope to monitor compositional changes. Results from the CST bioreactor showed that the biomass-specific ATP concentration increases from 0.44 to 1.86 mg ATP g(-1) dry weight (dw) as dilution rate increases from 0.027 to 0.115 h(-1). At this upper dilution rate the cells were washed out. The specific ATP concentration reached a limiting average value of 1.73 mg ATP g(-1) dw, which is assumed to be the quantity of ATP in 100% viable biomass. In the TPAL bioreactor, the ATP level increased with dilution rate in both the immobilized and suspended biomass. The specific ATP concentration in the immobilized biomass increased from approximately 0.051 mg ATP g(-1) dw at dilution rates between 0.111 and 0.200 h(-1) to approximately 0.119 mg ATP g(-1) dw at dilution rates between 0.300 and 0.500 h(-1). This indicates that the immobilized biomass contained a viable cell fraction of around 5%. Based on these results, kinetic data for freely suspended cells should not be applied to the modeling of immobilized cell systems on the assumption that immobilized biomass is 100% viable. (c) 1993 John Wiley & Sons, Inc.     

Short day lengths alter stress and depressive-like responses,and hippocampal morphology in Siberian hamsters

Many psychological disorders comprise a seasonal component. For instance, seasonal affective disorder (SAD) is characterized by depression during autumn and winter. Because hippocampal atrophy may underlie the symptoms of depression and depressive-like behaviors, one goal of this study was to determine whether short days also induce structural changes in the hippocampus using photoperiod responsive rodents — Siberian hamsters. Exposure to short days increases depressive-like responses (increased immobility in the forced swim test) in hamsters. Male hamsters were housed in either short (LD 8:16) or long days (LD 16:8) for 10 weeks and tested in the forced swim test. Brains were removed and processed for Golgi impregnation. HPA axis function may account for photoperiod-related changes in depressive-like responses. Thus, stress reactivity was assessed in another cohort of photoperiod-manipulated animals. Short days reduced soma size and dendritic complexity in the CA1 region. Photoperiod did not induce gross changes in stress reactivity, but an acute stressor disrupted the typical nocturnal peak in cortisol concentrations. These data reveal that immobility induced by exposure to short days is correlated with reduced CA1 cell complexity (and perhaps connectivity). This study is the first to investigate hippocampal changes in the context of short-day induced immobility and may be relevant for understanding psychological disorders with a seasonal component.     

Reentrainment in Golden Hamsters: Effect of Melatonin, Age and Neonatal Clomipramine Treatment

Golden hamsters (young: 3 month-old; old: more than 12 month-old; or neonatally treated with clomipramine - a serotonin/noradrenaline re-uptake inhibitor antidepressant) were initially entrained to a 14:10 light:dark cycle, and their reentrainment rate after a 6 h phase advance in the photoperiod was determined. Animals took between 6 and 9 days to reentrain. Melatonin (1 mg/kg, i.p.) accelerated reentrainment to the LD cycle in all groups, except for the clomipramine-treated hamsters. These results support an important accelerating effect of the pineal hormone melatonin on resynchronization, no longer observed in clomipramine-treated hamsters.     

Short day lengths alter stress and depressive-like responses, and hippocampal morphology in Siberian hamsters

Many psychological disorders comprise a seasonal component. For instance, seasonal affective disorder (SAD) is characterized by depression during autumn and winter. Because hippocampal atrophy may underlie the symptoms of depression and depressive-like behaviors, one goal of this study was to determine whether short days also induce structural changes in the hippocampus using photoperiod responsive rodents — Siberian hamsters. Exposure to short days increases depressive-like responses (increased immobility in the forced swim test) in hamsters. Male hamsters were housed in either short (LD 8:16) or long days (LD 16:8) for 10 weeks and tested in the forced swim test. Brains were removed and processed for Golgi impregnation. HPA axis function may account for photoperiod-related changes in depressive-like responses. Thus, stress reactivity was assessed in another cohort of photoperiod-manipulated animals. Short days reduced soma size and dendritic complexity in the CA1 region. Photoperiod did not induce gross changes in stress reactivity, but an acute stressor disrupted the typical nocturnal peak in cortisol concentrations. These data reveal that immobility induced by exposure to short days is correlated with reduced CA1 cell complexity (and perhaps connectivity). This study is the first to investigate hippocampal changes in the context of short-day induced immobility and may be relevant for understanding psychological disorders with a seasonal component.     

Influence of short days on diurnal patterns of serum gonadotrophins and prolactin concentrations in the male Djungarian hamster, Phodopus sungorus

Exposure to short days for 8 weeks suppressed mean serum concentrations of FSH, LH and prolactin compared to hamsters kept in long days. Hamsters in short days exhibited a small afternoon rise in serum FSH, but serum LH and prolactin did not exhibit 24-h variations. In hamsters under long days, a late afternoon-early evening increase was evident for circulating prolactin but none was detected for the gonadotrophins. A fall in testes weights rapidly occurred by 14-28 days after transfer to short days. This was accompanied or preceded by a decrease in serum gonadotrophins and prolactin. Reductions in serum FSH and LH occurred in short days in blood samples taken at 09:00 h or 15:00 h. However, the nadir in serum prolactin was first achieved (at 09:00 h), at least 7 days before that at 15:00 h (i.e. Day 14 versus Day 21 of short photoperiod, respectively). The ability to secrete gonadotrophins was further tested in hamsters that had undergone gonadal regression. Castration of hamsters exposed to short days or injected with melatonin in the afternoon, a treatment known to mimic short day effects, induced a 3- to 5-fold increase in serum gonadotrophins. However, this rise in FSH and LH was significantly attenuated compared to the 10-fold response in controls in long days. The results indicate that gonadal involution induced by short days may be mediated by the decline in mean gonadotrophin secretion which, in turn, is regulated by responsiveness to steroids, as well as a mechanism independent of the negative feedback action of gonadal steroids.     

Reentrainment in Golden Hamsters: Effect of Melatonin,Age and Neonatal Clomipramine Treatment

Golden hamsters (young: 3 month-old; old: more than 12 month-old; or neonatally treated with clomipramine – a serotonin/noradrenaline re-uptake inhibitor antidepressant) were initially entrained to a 14:10 light:dark cycle, and their reentrainment rate after a 6 h phase advance in the photoperiod was determined. Animals took between 6 and 9 days to reentrain. Melatonin (1 mg/kg, i.p.) accelerated reentrainment to the LD cycle in all groups, except for the clomipramine-treated hamsters. These results support an important accelerating effect of the pineal hormone melatonin on resynchronization, no longer observed in clomipramine-treated hamsters.     

Infectivity, growth, development and pathology of Echinostoma caproni (Trematoda) in the golden hamster

Laboratory hamsters (Mesocricetus auratus) were experimentally infected with 75 ± 15 metacercarial cysts of Echinostoma caproni. Worms were recovered from days 7 to 89 post-infection with eight to 90 (average 37) parasites in the small intestine. Worm wet weights averaged 0.85 mg at 10 days, 1.8 mg at 17 days, 3.4 mg at 45 days, and 7.7 mg at 89 days; average dry weights for the identical days were, 0.15, 0.30, 0.70 and 2.2 mg, respectively. The average body area of worms fixed in hot (80°C) alcohol-formalin-acetic acid was 0.21 mm² on day 3, 4.9 mm² on day 10, and 17.7 mm² on day 42. Clinical signs in some hamsters included progressive unthriftiness and watery diarrhea. Gross examination revealed enlarged lymphatic nodules along the length of the small intestine. The histopathological responses of hamsters to the parasite showed erosion of the intestinal villi with lymphocytic infiltration being the primary response; hemorrhagic areas were also observed in the villi.     

Viremia and serum antibodies in Macacus rhesus monkey after inapparent infection with European tick-borne encephalitis virus.

1. Inapparent infection was called forth in M. rhesus monkeys by means of subcutaneous inoculation of ETBE virus. 2. Viremia was found in 18 (86 per cent) of 21 monkeys. In all the 18 monkeys, specific virus-neutralizing antibodies were found; in 17 of them complement-fixing antibodies developed in addition. 3. Neutralizing antibodies (N greater than or equal to 1.7 log10) were first recorded on 10th day with a peak on 32nd day, retaining, after a small decrease, a relatively high level in all reacting animals. 4. Complement-fixing antibodies were first found on 18th day, showing a peak on 22nd day whereafter they dropped considerably or even disappeared so that on 150th day they were present in a low titre in only 35 per cent of the originally reacting monkeys. 5. The findings were compared with the situation in naturally infected humans and in hamsters infected inapparently (experimentally) with ETBE virus.     

Expression of the preproenkephalin A gene in the heart of cardiomyopathic hamsters.

The expression of the preproenkephalin A gene (Enk gene), which codes for the precursor of enkephalins, was investigated in the heart of hamsters with a hereditary cardiomyopathy at four different stages of the disease: the prenecrotic stage (30 days), the necrotic stage (60 days), the hypertrophic stage (120 days), and the final stage (200 days). In control atria and ventricles, the relative abundance of the Enk mRNA, as assessed by Northern blot analysis, did not change upon ageing. In the ventricles of cardiomyopathic hamsters, however, it increased about two- to three-fold at the necrotic stage, but was unaltered at the other time points studied; whereas in the atria, it progressively decreased to reach about half that of control hamsters at the final stage. Enkephalin levels, as measured by radioimmunoassay, decreased at 60 days in both the atria and ventricles of control hamsters, and also in the atria of cardiomyopathic hamsters, and remained stable thereafter, corresponding to one-third to one-half of those at 30 days. However, in the ventricles of cardiomyopathic hamsters, the peptide level decreased only slightly, the consequence being that at 60, 120, and 200 days, it was about two- to three-fold that of control hamsters. The lack of correlation between peptide levels and the relative abundance of the Enk mRNA suggests that translational and (or) post-translational mechanisms are important in the control of the expression of the Enk gene in the heart of hamsters.     

Elimination of short-day melatonin signaling accelerates gonadal recrudescence but does not break refractoriness in male Turkish hamsters

Long days stimulate and short days (SDs) inhibit the reproductive axis of photoperiodic rodents. In long-day Turkish hamsters, unlike most other rodents, elimination of pineal melatonin secretion by constant light or pinealectomy initiates a cycle of gonadal involution and recrudescence outwardly similar to that induced by short days. The present study assessed whether short days and constant light induce the seasonal reproductive cycle via common or different interval timing mechanisms. Male hamsters that had undergone gonadal involution in SDs for 8 or 14 weeks were treated with LL for 14 and 8 weeks, respectively. If SDs and LL act via independent mechanisms, then gonadal quiescence of SD-regressed males, which normally lasts 10 weeks, might be extended by LL treatment; alternatively, if SDs and LL act on the same timer, or the timer cannot be retriggered, then LL will not extend the duration of reproductive quiescence. Neither of these outcomes materialized. Instead, male hamsters exposed to LL while reproductively quiescent exhibited accelerated gonadal recrudescence. Extended LL treatment did not restore responsiveness to SDs in photorefractory hamsters. In Turkish hamsters, photoperiodic history determines whether constant light inhibits or stimulates the hypothalamic-pituitary-testicular axis.     

Termination of gonadal refractoriness in Turkish hamsters, Mesocricetus brandti

The Turkish hamster (Mesocricetus brandti) is a photoperiodic species. In this investigation, we characterized the photoperiodic requirements for termination of gonadal refractoriness, defined as the inability of the animal to respond to short-day treatment with gonadal regression. Paired testes weights were reduced to less than 20% of their original weight by 10 wk of 12L:12D treatment. This was followed by spontaneous testicular recrudescence (completed by Week 25 of 12L:12D treatment), the overt indication of refractoriness to short photoperiods. Next, the period of long-day exposure sufficient for termination of refractoriness was determined. Refractory males were exposed to 16L:8D for 5 to 20 wk. Ten weeks of 16L:8D treatment was enough for the animals to regain the sensitivity to a second challenge of 12L:12D treatment. Fifteen weeks of 20L:4D or 16L:8D terminated refractoriness in female Turkish hamsters; 20L:4D therefore was not interpreted as a short day by refractory hamsters. This was unexpected because in photosensitive animals this photoperiod acts like a short day, causing gonadal regression. These results suggest that Turkish hamsters are similar to Syrian hamsters in that both species require two or more months of long days in summer to recover sensitivity to the short days of the following fall.