Age-related changes of the ultrastructure in the cardiomyopathic hamster (UM-X7.1 Syrian hamster) parathyroid gland

We qualitatively and quantitatively investigated parathyroid glands of the UM-X7.1 cardiomyopathic hamster at 1, 2, 6 and 12 months of age to compare them with those of the normal hamster. We found that at 1 month of age in the UM-X7.1 hamster, the Golgi apparatus, lipid droplets and secretory granules decreased. There were no significant differences between the UM-X7.1 hamster and the control hamster at 2 months of age. At 6 months of age, the Golgi apparatus, rER and the secretory granules significantly increased in the UM-X7.1 hamster. At 12 months of age, the Golgi apparatus and lysosomes increased, while the secretory granules decreased. Ultrastructurally, we consider that in the UM-X7.1 hamster, the synthesis and release of the parathyroid at 6 months of age may be activated by an excessive amount of circulating catecholamine, and the functional activity of the parathyroid glands at 12 months of age may be depressed by the increased plasma calcium level. These findings suggest that the activities of the synthesis and release of the parathyroid hormone were the highest at 6 months of age in the UM-X7.1 hamster.     

Effects of dietary selenium on lipid peroxidation, mitochondrial function and protein profiles in the heart of the myopathic Syrian golden hamster (BIO 14.6)

Male, weanling myopathic Syrian Golden Hamsters (BIO 14.6 strain) were fed a selenium-adequate diet (controls) or this diet supplemented with 1.0 ppm selenium (treated) for 30 days. Se-treated animals exhibited a 50% reduction in lipid peroxidation in heart homogenates relative to controls and a 61% increase in mitochondrial glycerophosphate acyltransferase activity. Gel electrophoresis revealed no alterations in cardiac protein profiles from treated or control animals. These data suggest that the selenium prevents peroxidative injury and maintains mitochondrial function in the absence of alterations in cardiac proteins.     

Increased compliance in diaphragm muscle of the cardiomyopathic Syrian hamster

We investigatedthe hypothesis that diaphragm compliance was abnormal incardiomyopathic Syrian hamsters (CSH), an experimental model ofmyopathy. The passive elastic properties of isolated diaphragm muscleswere analyzed at both the muscle and sarcomere levels. We used thefollowing passive exponential relationship between stress () andstrain ():  = (E_o/)(e  1), where E_o is the initialelastic modulus and  is the stiffness constant. Immunocytochemistryprocedures were used to analyze the distribution of two key elasticcomponents of muscle, extracellular collagen and intracellular titinelastic components, as well as the extracellular matrix glycoproteinlaminin. Muscle and sarcomere values of  were nearly twofold lowerin CSH (8.7 ± 1.9 and 8.3 ± 1.4, respectively) than in controlanimals (19.7 ± 1.7 and 16.8 ± 2.1, respectively)(P < 0.01 for each). Compared withcontrols, E_o was higher in CSH.Sarcomere slack length was significantly longer in CSH than in controlanimals (2.1 ± 0.1 vs. 1.9 ± 0.1 µm,P < 0.05). The surface area ofcollagen I was significantly larger in CSH (17.4 ± 1.8%) than incontrol animals (12.4 ± 0.7%, P < 0.05). There was no change in the distribution of titin or lamininlabelings between the groups. These results demonstrate increaseddiaphragm compliance in cardiomyopathic hamsters. The increase in CSHdiaphragm compliance was observed despite an increase in the surfacearea of collagen and was not associated with an abnormal distributionof titin or laminin.

     

Reentrant tachyarrhythmias in right atria of cardiomyopathic versus healthy Syrian hamster

We studied the role of acetylcholine (ACh) and calcium overload in the induction of atrial flutter or atrial fibrillation (AF) in right atria from 34 normal male Syrian hamsters (F1B) and 33 cardiomyopathic Syrian hamsters (BIO 14.6) associated with focal myocardial necrosis. Action potential (AP) was recorded with conventional microelectrode techniques and twitch force by a transducer. ACh (0.1, 1 and 10 µM) induced high-frequency AF (around 33 Hz) along with tension oscillations and contracture in 7 of 12 normal hamster atria. These effects of ACh were abolished by tetrodotoxin or quinidine as well as by atropine. In contrast, ACh induced AF only in 1 of 12 myopathic atria. In both normal and myopathic atria, ACh induced similar changes in AP duration, spontaneous rate and force. The effects of calcium overload were tested by means of a high [Ca²⁺]_o (8.1 mM) low [K⁺]_o (1 mM) solution in another series of experiments. This solution also induced incidence of AF higher in normal (10/12) than in myopathic atria (4/12). The calcium load was also increased by high-frequency pacing (32 Hz for 3 or 30 s): AF occurred in normal atria (5/8), but not in myopathic atria (0/8). Measurement of the refractory period revealed a longer refractory period in myopathic than in control atria. We concluded that the lower incidence of AF in myopathic atria was probably due to their longer refractory period and the associated focal myocardial necrosis which then hindered the establishment of such a reentrant rhythm.     

A metabolic approach to the treatment of dilated cardiomyopathy in BIO T0-2 cardiomyopathic Syrian hamsters

Mechanisms underlying dilated cardiomyopathy (DCM) are poorly understood and effective therapy is still unavailable. The aim of this study was to examine the heart ultrastructure and dynamic of BIO T0-2 cardiomyopathic hamsters, an animal model of DCM, and to study in these animals, the effects of a co-formulation (HS12607) of propionyl-L-carnitine, coenzyme Q(10) and omega-3 fatty acids on cardiac mechanical parameters. Sarcomere length, Frank-Starling mechanism and force-frequency relations were studied on isolated ventricular papillary muscle from age-matched BIO F1B normal Syrian hamsters, BIO T0-2 control and BIO T0-2 HS12607-treated cardiomyopathic Syrian hamsters. At the optimum length to maximum active force, electron microscopy of left ventricular papillary muscle revealed that seven out of ten muscles studied showed shorter sarcomeres (1.20 +/- 0.29 microm), and the remaining three showed longer sarcomeres (2.80 +/- 0.13 microm), compared to those of normal hamsters (2.05 +/- 0.06 microm, n = 10). Severe alterations of the Frank-Starling mechanism, force-frequency relations and derivative parameters of contractile waves were also observed in vitro in the BIO T0-2 control hamsters. Long-term (8 weeks) treatment with HS12607 prevented alterations in sarcomere length in the BIO T0-2 cardiomyopathic hamsters; the Frank-Starling mechanism and force-frequency relations were also significantly (P < 0.05) improved in these hamsters. Therefore results of the present study strongly suggest the need for clinical studies on metabolic therapeutic intervention in the effort to stop the progression of dilated cardiomyopathy.     

Age- and myopathy-dependent changes in connexins of normal and cardiomyopathic Syrian hamster ventricular myocardium

The conduction of cardiac action potentials depends on the flow of excitation through gap junctions, which are hexameric protein associations of connexins (Cxs). The major Cx reported in the heart is Cx43, although some Cx40 and Cx45 are also present. There is some evidence for altered Cx content in heart failure. In heart failure, conduction is depressed and slowed conduction may contribute to arrhythmogenesis and (or) the maintenance of arrhythmia. Cx content and distribution were determined in ventricular tissues from normal and cardiomyopathic Syrian hamsters, an animal model of heart failure which has reproducible age-specific cardiomyopathy resulting in heart failure and age-matched controls in three groups: young (3-5 weeks), adult (13-18 weeks), and old (>45 weeks). Frozen, unfixed sections of ventricular tissues were immunofluorescently stained using antibodies against Cx43, Cx40, and Cx45. Cx43 was the predominant Cx detected in all samples. In normal hamsters, Cx43 was localized predominantly at the intercalated disc region, while in myopathic myocytes, it was scattered. In Western blots, Cx43 content of normal hamster hearts was highest in the adult hearts compared with young and old hamster hearts. In contrast, Cx43 content was significantly lower in adult cardiomyopathic hamster hearts compared with all other groups. The alterations of content and distribution of gap junction Cx43 may contribute to diminished conduction, pump function, and arrhythmogenesis in heart failure.     

Growth in the myopathic Syrian hamster (Cricetus auratus)

The objective was to assess the effect of the hereditary myopathic disease (muscular dystrophy) on 4 growth parameters: body-weight, head-body length, skull weight and cranial length in the Syrian hamster over a 4-13 month period. A control colony of 34 males and 32 females was compared to a muscular dystrophy colony consisting of 37 males and 27 females. The monthly means of the 4 growth parameters were computed and full data were used for computations of analysis of variance with regression of each group, sex and growth parameter. Intersex and intergroup comparisons of the same parameters were made using analysis of covariance. In the controls, the male bodies were heavier and longer than the female bodies; males grew over the total period. In dystrophic hamsters, males were heavier than females, but females were longer. In both control and dystrophic hamsters, female skulls were longer and heavier. In all parameters the means of the control colony were greater than those of the dystrophic colony relative to age. The disease factor in the muscular dystrophy colony adversely influenced all 4 growth parameters.     

Estrogen carcinogenesis in Syrian hamster tissues: role of metabolism

Evidence for a role of estrogen metabolism in hormonal carcinogenesis was obtained with the Syrian hamster as an in vivo model system. Both natural and synthetic estrogens are capable of inducing a high incidence of renal carcinomas in this species. A high incidence of hepatocellular carcinomas can also be induced in the hamster with synthetic estrogens such as ethinyl estradiol or diethylstilbestrol, provided alpha-naphthoflavone (ANF) is present in the diet. Although steroid receptor-mediated hormonal events appear to be intimately involved in the process of in vivo cell transformation of both tissues, certain observations strongly suggest that nonhormonal events are also important. Despite their potent estrogenic activity at the doses used, ethinyl estradiol and alpha-zearalanol induce relatively low renal tumor incidences after 9.0 and 10.0 months of continuous treatment, respectively. A role for the metabolism of estrogens to reactive intermediates is also suggested by studies showing estrogen-induced renal tumorigenesis can be partially inhibited by concomitant administration of ANF or ascorbic acid. Consistent with this is the general correlation between the amount of catechol estrogen formed by a compound, as mediated by estrogen 2-/4-hydroxylase, and renal carcinogenicity data. Recently, additional supporting evidence has been obtained from studies involving the irreversible binding of reactive metabolites of steroidal or stilbene estrogens to hamster liver microsomal proteins.     

Experimental iron deficiency in Syrian hamsters (Mesocricetus auratus)

An animal model was developed in which the effect of iron deficiency on the oral mucosa could be studied. Iron deficiency was induced by feeding hamsters a low-iron powdered diet together with withdrawal of 0.5 ml of blood weekly, for a period of 9 weeks. At the end of this period the mean haematological values for control animals were, Hb 15.9 g/dl, plasma iron 40.3 mumol/l, TIBC 90.5 mumol/l and transferrin saturation 44.5%, compared with 7.4, 7.2, 111.4 and 6.5 respectively for experimental animals. These results were reproducible in successive groups of animals and indicate that this is a useful model for the study of iron deficiency anaemia.     

Cytological sub-division of S-phase in the Syrian hamster (Mesocricetus auratus)

Using BrdU/Hoechst 33258/Giemsa methods for detecting replicating chromosome bands, a method is described by which the DNA synthesis phase may be sub-divided on the basis of distinctive patterns displayed by certain chromosomes. — Applied to asynchronous populations successively sampled through one cell cycle, cells in S can be unscrambled and replaced in their correct time sequence. — This helps to overcome the sampling-time variable inherent in such populations, and allows a clearer picture of the progression of events both qualitatively and quantitatively.     

Chromosome replication in fibroblasts of the Syrian hamster (Mesocricetus auratus)

The BrdU/Hoechst 33258/Giemsa method for sub-dividing S-phase in asynchronous cell populations has been re-evaluated and modified to give better definition and more even distribution of sub-phases. A reference pattern of early-relicating euchromatic bands is given for all chromosomes at Sk2 in primary cultures of skin fibroblasts. The overall band patterns at each sub-phase have allowed more objective definitions of early and late replication for these cells, and show that in both classes of chromatin light G-bands preceed dark G-bands. Asynchrony between homologous bands is observed at all stages of S, albeit with a variable frequency. The observed in vitro replication patterns and programme for the chromosomes of skin fibroblasts does not appear to be affected by the age or sex of the source.     

Variation in the growth of the preweaning Syrian hamster (Cricetus auratus)

An assessment of the growth rate spectrum based on a longitudinal weight study of golden hamsters was undertaken over the preweaning period. The period covered 23 days with data probes at 24-hourly intervals and encompassed 16 litters providing a birth number of 120 young and a weaning survival number of 82. Subsequent analysis directed initially at the pooled or averaged data showed sex differences with males gaining weight faster than females. Further analysis showed the total period to have three definitive break-points and therefore four phases of growth activity. The segmented linear regression line calculations showed that the phasic duration of males in the second and third phases were two days later than the females. Following data-analysis adjustments and taken into account aberrations of the sample, final indications pointed to the preweaning hamster growth spectrum as quadrophasic, exhibiting a stable first phase, a second and third phase terminating earlier in females and a final weaning weight being heavier in males. The growth curves demonstrated a 'U' shaped outline and formed an integral part of hamster preweaning precocity.     

Photoperiodic control of meiosis in the male Syrian hamster (Mesocricetus auratus)

Male Syrian hamsters exposed to short photoperiods of 6 h light/day (6L:18D) show regression of the testes within 12 weeks. Chromosome preparations of the meiotic stages (pachytene, metaphase I (MI) and metaphase II (MII)), testicular weights relative to body weights, sperm counts, seminiferous tubule diameter and histological appearance were examined at intervals during regression and subsequent recovery in a long photoperiod (14L:10D). The fall of testicular weight was associated with the decrease in tubule diameter. Spermatogenesis and sperm count were reduced rapidly and finally ceased after 10 weeks in short days. The numbers of MI and MII cells relative to 100 pachytene cells progressively decreased during the short-day treatment, although the ratio of MI:MII stayed constant whenever there was meiotic activity (except in the first week of the recovery phase). This suggests that an increasing proportion of pachytene cells did not progress to MI with increased time in short days, but cells which did reach MI progressed to MII in the same proportions as in the control testes. Meiosis ceased after 10 weeks in short days. Recovery in the long days was marked by a peak in the number of MI and MII cells/100 pachytene cells soon after the return to long days. This preceded the return (to control values) of the sperm count by 10 weeks. Initial recovery in the first 3 weeks was very rapid in all the determined values.