Maternal entrainment of the developing circadian system in the Siberian hamster (Phodopus sungorus)

The aim of these studies was to investigate maternal entrainment of developing circadian locomotor activity rhythms in the Siberian hamster. In Experiment 1, mothers were transferred from a 16:8 LD cycle into constant dim red light (DD) from the day of parturition, and wheel-running activity of the mother and pups was individually monitored from the time of weaning. The phases of the individual pups' rhythms were found to be synchronized both to the phase of the mother and to the phase of lights off (ZT 12) of the photo cycle that the mother was exposed to until the day of parturition. To investigate whether this synchrony might reflect direct effects of light acting upon the fetal circadian system in late gestation, the experiment was repeated but with mothers placed into DD early in pregnancy (< or = day 7 of gestation). The results were similar to the first study, suggesting that the mother rather than the photo cycle during the latter part of gestation entrains the developing circadian system. The third experiment investigated whether this entrainment occurred during the postnatal period. Breeding pairs were maintained on alternative light-dark cycles, LD and DL, that were 12 h out of phase. Litters born to mothers on one light-dark cycle were exchanged on the day of birth with foster mothers from the reversed light-dark cycle, then raised in DD. Control litters exchanged between mothers from the same light-dark cycle had similar litter synchrony as shown by nonfostered litters of Experiment 1. However, pups cross-fostered with mothers on reversed LD cycles showed a very different distribution of pup phases. Pups were not synchronized to their natural mother but to their foster mother. Moreover, pups were more scattered over the 24-h period and were found to be significantly synchronized to the phase of the reversed LD cycle. These results demonstrate the occurrence of postnatal entrainment in the Siberian hamster. The increased scatter produced by the cross-fostering paradigm results from some litters being completely entrained to the phase of the foster mother, some with an intermediate distribution between the phase of the natural and foster mothers, and a minority being associated with the phase of the natural mother. These results suggest that Siberian hamster pups are initially synchronized either prenatally or at birth but that the mother continues to provide entrainment signals during the postnatal period.     

Tyrosine hydroxylase- and/or aromatic L-amino acid decarboxylase-containing cells in the suprachiasmatic nucleus of the Syrian hamster (Mesocricetus auratus)

We assessed forearm vascular and blood pressure responses to dynamic leg exercise in patients 7 and 28 days postmyocardial infarction. To determine a possible association between abnormal exercise vascular responses and baroreflex dysfunction, integrated and carotid baroreflex sensitivity and forearm vascular responses (during application of subhypotensive lower body negative pressure) were assessed. On day 7, 42 patients were compared with 21 age- and sex-matched controls. All subjects were assessed for (1) forearm vascular resistance during semierect exercise, (2) blood pressure measurements during erect treadmill exercise, and (3) integrated, cardiopulmonary, and carotid baroreceptor sensitivity. These studies were repeated in 13 patients on day 28. Forearm vascular resistance increased during exercise by 36% +/- 63% in patients versus 121% +/- 105% in controls (P = 0.0001), and fell in 15 patients, a response seen in none of the controls. Exercise hypotension was demonstrated in 5 patients, all of whom had abnormal vasodilator vascular responses. Those patients with vasodilator responses had a lower left ventricular ejection fraction (52% +/- 12% vs 62% +/- 9%; P = 0.007), and lower cardiopulmonary mechanoreceptor sensitivity (-6.6 +/- 3.9 units vs +6.4 +/- 10.4 units, P = 0.02) than those with constrictor responses, respectively. In the 13 patients studied on day 28, the change in forearm vascular resistance was similar to that observed on day 7 (36% +/- 63% vs 46% +/- 73%). Paradoxical vasodilation of forearm vessels during leg exercise is common in patients studied 7 and 28 days postmyocardial infarction, and is associated with lower left ventricular ejection fraction and abnormal vascular responses during subhypotensive lower body negative pressure.     

Modulation of serotonin binding sites in the brain of the Djungarian hamster, Phodopus sungorus, during adaptation to a short photoperiod

During the physiological adaptation of the Djungarian hamster, Phodopus sungorus, to a short photoperiod in autumn the modulation of specific serotonin (5-HT) binding sites of synaptic membranes was investigated in two brain regions, i.e. cerebral cortex and basal brain (CNS without cerebral cortex, cerebellum, pineal gland, and spinal cord). The radioligands [3H]5-HT and [3H]ketanserin were used to characterize total 5-HT1 and 5-HT2 binding sites, respectively. An increase of 5-HT1 and 5-HT2 binding sites was observed in both brain regions within 14 days after reduction of the photoperiod from a 14:10 h light/dark (l/d) cycle to an 8:16 h l/d cycle. The increase was still present after 56 days of the short photoperiod. Binding kinetics assayed after 4 days of the short photoperiod show that maximal specific binding of [3H]5-HT and [3H]ketanserin was increased, while dissociation constants (KD) were not changed. The membrane anisotropy of synaptic membranes, measured by fluorescence polarization, was reduced transiently during the early part of the adaptation. Neither the phospholipids nor the mole ratio of cholesterol to phospholipids were significantly affected by adaptation to short photoperiod. The results suggest an important role of the central nervous 5-HT system in the physiological adaptation of the Djungarian hamster to a short photoperiod.     

Direct effects of the pineal hormone melatonin on testosterone synthesis of Leydig cells in Djungarian hamsters (Phodopus sungorus) in vitro

Leydig cells of adult Djungarian hamsters, stimulated with luteinizing hormone (LH), were co-incubated with melatonin at various concentrations in a primary culture system. Testosterone secretion was only affected by melatonin when cells were stimulated with LH. Maximal suppression was observed at low doses of LH (0.5 ng/ml). These effects are at least partially mediated through the adenylate cyclase system, since melatonin was able to reduce forskolin-stimulated testosterone secretion. These results indicate that the time between pulses of LH can be considered to be most highly effective for tonic melatonin actions.     

Daily and photoperiodic 2-125I-melatonin binding changes in the pars tuberalis of the Syrian hamster (Mesocricetus auratus): effect of constant light exposure and pinealectomy

To clarify the relationship between neural crest cells and various developmental eye abnormalities, pregnant mice were administered an intraperitoneal injection of 12.5 mg/kg retinoic acid (RA) suspended in corn oil on day 7 of pregnancy (RA group). Control mice received an equal volume of corn oil only (control group). The fetuses were removed by laparotomy on day 18 of gestation. The fetal mortality was 46.3% in the RA group and 2.2% in the control group. The live fetuses in both groups were observed grossly, and the eyes were examined histologically in serial sections. In the RA group, gross malformations were observed, including microphthalmos (95.5%), cleft lip and palate (36.4%), and central nervous system anomalies (31.8%). In the control group, these malformations were seen in only 6.7%, 0%, and 2.2%, respectively. Histologic examinations in the RA group revealed microphthalmos (47.7%), anophthalmos (38.6%), faulty closure of the embryonic fissure (36.4%), developmental abnormalities of the vitreous (34.1%), aphakia (22.7%), goniodysgenesis (18.2%), and faulty separation of the lens vesicle (15.9%). They were detected in only 3.3%, 1.1%, 3.3%, 8.9%, 1.l%, 2.2%, and 2.2%, respectively, of the control group. These developmental eye abnormalities arose from abnormal migration of neural crest cells.     

Dietary protein restriction and selective preference for a protein-containing diet in the golden hamster (Mesocricetus auratus)

The corrected midparental height method was introduced by Tanner in 1970 (Tanner method) and is commonly used to estimate target height in children to evaluate the effectiveness of growth-promoting therapies. It has not been established if the equation used to compute target height should be the same for children with short, normal, or tall parents. In this study, we examined the predicted target height values by parental heights in a large population-based study (n = 2402). A simple linear function of midparental height (x) was proposed to estimate target height (y): y = 45.99 + 0.78x (boys), y = 37.85+0.75x (girls), with a 95% predicted interval of about +/-10 cm. The prediction model was similar for boys and girls in SD scores (SDS), and was not affected by assortative mating or difference in parental heights. The model may underestimate the potential stature by about 2 cm for children with midparental height below -2 SDS, or 163 cm. In comparison, the Tanner method may lead to a 6-cm error in underestimating target height for these children. The function would be a better choice than the Tanner method for estimating target height in the clinical evaluation of growth promotion treatments because it is common that short children also have short parents. Children with very short parents will usually be much taller than their parents in adult stature, and we believe that a different function should be developed. The results support the proposed nondominant, non-sex-linked, polygenic inheritance in stature. The estimated heritability values were 0.75-0.78 in cm or 0.55-0.60 in SDS.     

Localization by immunoelectron microscopy of Schistosoma mansoni antigens in the glomerulus of the hamster (Mesocricetus auratus) kidney

Gene therapy has the potential to provide cancer treatments based on novel mechanisms of action with potentially low toxicities. This therapy may provide more effective control of loco-regional recurrence in diseases such as non-small cell lung cancer (NSCLC), as well as systemic control of micrometastases. Despite current limitations, retroviral and adenoviral vectors can in certain circumstances provide an effective means of delivering therapeutic genes to tumour cells. Although multiple genes are involved in the process of carcinogenesis, mutations of the p53 gene are the most frequent abnormality identified in human tumours. Pre-clinical studies both in vitro and in vivo have shown that restoration of p53 function can induce apoptosis in cancer cells. Phase I clinical trials now show that p53 gene replacement therapy is feasible and safe using both retroviral and adenoviral vectors, and that it induces tumour regression in patients with advanced NSCLC and recurrent head and neck cancer. Other pre-clinical studies indicate that gene therapy may have useful synergy with cytotoxic and radiation therapy. This paper describes the different gene therapy strategies under investigation and the pre-clinical data that provides a rationale for the gene replacement approach, reviews clinical trial data and presents novel ideas for improving current vectors and gene delivery to tumours.     

The development of the cerebellar cortex of the Syrian hamster, Mesocricetus auratus. Foliation, cytoarchitectonic, Golgi, and electron microscopic studies

Although a number of investigations of abnormalities of cerebellar development have been carried out in the hamster, no detailed Golgi or ultrastructural studies of cerebellar development in this species have been reported. This report describes the development of the hamster cerebellar cortex from birth (day 0) through postnatal day 78, as studied by light, Golgi, and electron microscopic methods. Foliation patterns correlate with the expansion of the cerebellar layers and of total cerebellar area. Cytologic and morphologic development of the major cerebellar cell types--Purkinje, Golgi, basket, stellate, granule, and Bergmann glial cells--correlate with those of other species, such as the rat and mouse. Electron microscopic observations at selected developmental ages allow identification and classification of synapses in the early postnatal hamster. Parallel fiber and climbing fiber synapses are already present at birth. Although synaptogenesis probably continues through the first two postnatal months, all major cell types have developed initial synapses by postnatal day 6, at a time when little cellular maturation has occurred. By using gestational rather than natal age, close developmental correlations between hamsters and rat and mouse are possible. Since the gestational period of the hamster is only 16 days, the hamster cerebellum is less mature at birth than that of either the rat or mouse. Thus, the hamster is a convenient animal in which to investigate the effects of various procedures on early cerebellar development.     

Monoclonal antibody-based immunohistochemical demonstration of Entamoeba histolytica in liver tissues of experimentally infected hamster (Mesocricetus auratus)

Histopathological changes and the presence of Entamoeba histolytica trophozoites was sequentially followed after intrahepatic inoculation of the parasites in 42 hamsters, 35 of which received no treatment whereas the remaining seven were treated with metronidazole. The liver tissues were examined for amoebic trophozoites by a monoclonal antibody (mAb)-based immunofluorescence assay (IFA), a mAb-based immunoperoxidase (IPx) and H & E staining. The number of hamsters developing abscesses was increased with time and was highest on day 30. Cellular infiltration with inflammatory cells and glycogen depletion were observed as early as day 5, followed thereafter by more intense inflammation of portal canals, periportal fibrosis, bile duct proliferation and hepatocyte degeneration. In 7 metronidazole-treated hamsters, no obvious pathological damage was seen. In a group of seven hamsters each, both IPx and IFA were positive in 3, 3, 4, 5 and 4 hamsters and in 3, 4, 3, 3 and 5 hamsters on days 5, 10, 15, 20 and 30, respectively. In 18 control hamsters, IPx, IFA and H & E were all negative. If the result from H & E was used as a gold standard, agreement between H & E and IFA and H & E and IPx were 91.4%, and 88.6%, respectively. Sensitivity and specificity were 93.8% and 89.5%, respectively for IFA, and 93.8% and 84.2%, respectively for IPx.     

Circadian rhythms of locomotor activity in the golden hamster (Mesocricetus auratus) measured with two different techniques.

Compared running wheels and spring-suspended cages as measurement devices for evaluating circadian locomotor activity rhythm. 12 golden hamsters were tested individually in a spring-suspended cage; 6 also had access to running wheels. Ss were exposed to 5 different levels of constant illumination, each condition lasting for several wks, and to a light-dark cycle. The onset of activity in the spring-suspended cage preceded the onset of activity in the running wheel by an amount which is a function of the circadian period. The increment by which the period changes in response to changes in light intensity equals, approximately, the changes of the interval between the 2 onsets. Animals with access to a running wheel show a tendency towards longer circadian periods. (16 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ultrastructure of proliferative ileitis in hamsters (Mesocricetus auratus)

The ileum of affected hamsters bore microvilli which were much shorter, less regularly arranged and less densely packed than those from control animals. Organelle derangements such as atrophy of mitochondria, degranulation and dilated cisterna of endoplasmic reticulum, were observed. Some hyperplastic epithelial cells contained multiple intracytoplasmic inclusion bodies and amyloid deposits were present extracellularly.     

1,25(OH)2 vitamin D3 binding sites in male sex organs of the Siberian hamster (Phodopus sungorus). An autoradiographic study

Using autoradiography, binding sites for 1,25(OH)2 vitamin D3 are found in certain genital organs of male Siberian hamsters (Phodopus sungorus), in particular in basal epithelial cells and fibroblasts of the lamina propria of prostate glands. Scattered labeled cells are also present in the epithelium of coagulation and urethral glands. In contrast to the findings in mice, under the conditions of the experiment, 1,25(OH)2 vitamin D3 binding sites are not recognizable in other accessory sex glands and gonads. The frequency of basal epithelial cells with [3H]1,25(OH)2 vitamin D3 nuclear binding is higher in regressed dorsal prostate glands of animals living in short photoperiods. The data suggest that 1,25(OH)2 vitamin D3 may promote proliferation and differentiation in basal epithelial cells, modulated by the seasonal and functional status of the animal.     

In vitro analysis of oocyte cumulus complex pickup rate in the hamster Mesocricetus auratus

In mammals, the oocyte and its surrounding cumulus cells constitute on oocyte cumulus complex (OCC). During ovulation, OCCs are extruded into the peritoneal or bursal cavity, depending on the species, and are then rapidly picked up by the fimbria on the outer surface of the oviductal infundibulum and transported to the ampulla, where fertilization occurs. We developed a method to measure OCC pickup rates quantitatively in vitro, and we used this method to evaluate the effects of viscosity and temperature on pickup rates. Hamster infundibula are placed in a holding pipette in a chamber modified to study OCC pickup. Ciliary beat frequencies (CBF) can be measured in the same preparation. Pickup rates vary depending on the pathway on which the OCC travels over the surface of the infundibulum; however, rates for a given pathway are very consistent. The average pickup rate at room temperature calculated from three different pathways/infundibulum was 55.2 +/- 10.6 microns/sec. Both rates between infundibula from the same female and rates among infundibula from different females were in most cases similar. Preparations preincubated in vitro for 2.75 hr produced rates similar to nonpreincubated samples, while longer preincubation resulted in decreased rates. Inclusion of Ficoll in culture medium to increase viscosity caused a concentration-dependent decrease in both OCC pickup rate and in CBF. However, a significant decrease in OCC pickup rate was only observed at viscosities higher than those found in bursal fluid. When trials were run at physiological temperature (36.4 degrees C) rather ambient temperature, rates increased to 136.7 +/- 29.9 (SD) microns/sec. Linear regression analysis demonstrated a strong positive correlation (r = 0.94) between OCC pickup rate and temperature. The OCC pickup rate assay can be used experimentally, and should be valuable in evaluating factors that affect rate and in studies dealing with the mechanism of OCC pickup.     

Neuronal projections from the mesencephalic raphe nuclear complex to the suprachiasmatic nucleus and the deep pineal gland of the golden hamster (Mesocricetus auratus)

Neuronal projections from the mesencephalic raphe system to the suprachiasmatic nucleus and the pineal complex were mapped in this study of the golden hamster, by use of the anterograde tracer Phaseolus vulgaris-leucoagglutinin and the retrograde tracer cholera toxin subunit B. From the median raphe nucleus, a rostral projection ascended in the ventral part of the mesencephalon to continue in the medial forebrain bundle of the forebrain. Nerve fibres from this bundle innervated the ventral and medial parts of the suprachiasmatic nucleus. At the level of the interpeduncular nucleus of the mesencephalon, fibres of the ventral bundle bent dorsally to reach the epithalamic area and to continue in the forebrain in a periventricular position. Some of these fibres innervated the dorsal tip of the suprachiasmatic nucleus. The dorsal raphe nucleus was the origin of a nerve fibre bundle, located in the periaqueductal gray of the mesencephalon, innervating the deep pineal gland and pineal stalk. Injection of cholera toxin B into the suprachiasmatic nucleus labelled cells in the median raphe. Combination of the retrograde tracing from the suprachiasmatic nucleus and serotonin transmitter immunohistochemistry showed that some of the cholera toxin B-immunoreactive nerve cells also contained serotonin. Thus, this study of the golden hamster shows a serotonergic projection from the median raphe nucleus to the suprachiasmatic nucleus and a projection from the dorsal raphe nucleus to the deep pineal gland supporting physiological indications of an influence of serotonin on the photoreceptive circadian system of the brain.     

Novel patterns of progesterone and prolactin in plasma during the estrous cycle in the Djungarian hamster (Phodopus campbelli) as determined by repeated sampling of individual females

In contrast to results from previous research, a surge of progesterone (P4) on the afternoon of proestrus was consistently detected in Djungarian hamster females. However, the timing of maximal P4 levels varied from 1200 to 1900 h across females; this impeded detection of the surge in earlier studies. No role for P4 in the induction of behavioral receptivity was found. Behavioral receptivity was induced in ovariectomized females with physiological levels of estradiol typical of an estrous cycle (60-180 pg/ml). P4 did, however, terminate receptive behavior within 48 h. Prolactin (PRL) was present as surge levels on each day of the cycle except diestrus 1, during which PRL remained at basal levels in all females. This pattern distinguishes the Djungarian hamster from the rat and mouse, which have PRL surges only on the afternoon of proestrus, and the golden hamster, which has a PRL surge on each of the 4 days of the estrous cycle. Diestrus 1, with P4 high and PRL low, was clearly distinct from Day 2 of Djungarian hamster pregnancy, during which P4 is low and PRL is surging. Therefore, postcoital P4 levels change within 34 h and before rescue of the corpus luteum. As Day 2 of pregnancy is also the most sensitive time for a mate-removal pregnancy-blocking response in P. campbelli, this hormonal profile may be associated with sensitivity to those stimuli.     

Permeability of the pineal organ of the golden hamster (Mesocricetus auratus) to HRP with special reference to different types of blood capillaries

The pineal organ of the golden hamster consists of deep and superficial portions which are connected to each other by a stalk. The permeability of capillaries for horseradish peroxidase (HRP) injected intravenously was examined in sections of entire portions of the gland that cut either along coronal or sagittal planes. Two distinct portions of the parenchyma, i.e., dorsal major and ventral minor ones, were found in the superficial gland. Most of the capillaries in the dorsal portion were of the continuous type of endothelium, whereas those in the ventral portion were fenestrated. In the dorsal portion, HRP readily crossed the endothelium, permeated the basal lamina, flowed into the perivascular connective tissue space and intruded into the intercellular clefts of the parenchyma. In contrast, HRP was not found to penetrate through the endothelium of the capillaries in the ventral portion to reach the perivascular area, thereby leaving the intercellular clefts of the parenchyma free of HRP. In the deep gland the capillaries were exclusively of the nonfenestrated type. Intravenously injected HRP was prevented from crossing the endothelium by the tight junction. In some areas, HRP penetrated through the capillaries in the pia mater, and crossed the outer limiting membrane to reach the intercellular clefts of the parenchyma and the basal lamina of the capillaries in the peripheral region of the deep pineal gland. The junctions between endothelial cells were not penetrated by HRP. The observations indicate that the type of capillary, absence of perivascular spaces, and permeability in the deep pineal are all similar to these factors in the general brain tissue; they differ from these in the superficial pineal gland, in which the dorsal portion shows characteristics found in other endocrine glands, but the ventral zone exhibits a unique situations: the presence of a blood-pineal barrier with a pericapillary connective tissue area.     

Corticotropin-releasing factor type II (CRF?) receptors in the bed nucleus of the stria terminalis modulate conditioned defeat in Syrian hamsters (Mesocricetus auratus).

In Syrian hamsters (Mesocricetus auratus), social defeat produces a subsequent increase in submissive and defensive behavior and a loss of normal territorial aggression, which the authors have called conditioned defeat. In this study, the authors investigated the effect of blocking corticotropin-releasing factor (CRF) Type I and Type II receptors on conditioned defeat. Intracerebroventricular infusion of the CRF? receptor antagonist antisauvagine-30 prior to testing significantly reduced conditioned defeat compared with vehicle controls, whereas the CRF? receptor antagonist CP-154,526 had no effect. Also, infusion of antisauvagine-30 into the bed nucleus of the stria terminalis (BNST) 15 min, but not immediately, prior to testing reduced conditioned defeat in a dose-dependent manner. The authors' results provide evidence that CRF? receptors in the BNST, but not CRF? receptors, are an important component in the neural circuitry regulating conditioned defeat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Improvements in the silver-staining technique for nucleolar organizer regions (AgNOR)

The silver-staining technique for nucleolar organizer regions (AgNOR) of Ploton et al., as popularized by Crocker, is being widely used for evaluation of nucleolar function, especially in neoplasia. It suffers from limited reliability, background staining, precipitates, and fading of the sections. Factors were identified that affect these problems. The oxidation-reduction level and gelatin used are particularly important. An improved procedure is presented which incorporates pre-reduction of the sections, selection of an optimal gelatin, and post-treatment of the sections to produce a permanent preparation. It is compatible with many fixatives and with other stains used before or after the silver stain.