Aged Guinea Pigs Research Articles

Effect of age and sensitivity to cholecystokinin on gallstone formation in the guinea pig

The purpose of this study was to evaluate the effect of age and the role of cholecystokinin therapy on gallstone formation in guinea pigs. Guinea pigs (31 1-mo-old, 31 1-yr-old, and 23 3-yr-old) were placed on a cholelithogenic diet for 2 wk while another 10 guinea pigs of each age group remained on regular chow. Half of each group received a daily injection of cholecystokinin (0.5 nmol/kg). After 2 wk, guinea pigs were killed and the gallbladders were examined for gallstones. The concentrations of bile constituents were determined. The prevalence of gallstones was: 1-mo-old, control 0 out of 16, cholecystokinin 1 out of 15; 1-yr-old, control 3 out of 14, cholecystokinin 5 out of 16; 3-yr-old, control 10 out of 11, cholecystokinin 3 out of 8. Gallstone formation was significantly greater in 3-yr-old controls than in the two younger control groups, and cholecystokinin treatment significantly reduced the incidence of gallstones to near the level seen in younger guinea pigs. In the two younger age groups (but not in the 3-yr-old group), the cholelithogenic diet significantly reduced the concentration of bile salts in bile below that of guinea pigs on a normal diet. The cholelithogenic diet and treatment with cholecystokinin did not alter the relative compositions of bile lipids from that of guinea pigs on a normal diet in any of the three ages studied. In the second experiment we measured gallbladder emptying in response to exogenous infusion of cholecystokinin-8 (100 fmol/kg/h-100 nmol/kg/h) in the same three age groups of guinea pigs in vivo that had been maintained on regular chow. There was no difference in cholecystokinin sensitivity between the two younger age groups, but both were significantly more sensitive to cholecystokinin than the 3-yr-old guinea pigs in rate of gallbladder emptying in the dose range 1 pmol/kg/h-1 nmol/kg/h. We conclude that a major factor in the increased incidence of gallstone formation in the aged guinea pig gallstone model is decreased allbladder emptying due to decreased gallbladder sensitivity to cholecystokinin.

Spontaneous reproductive tract leiomyomas in aged guinea-pigs

Seven of 83 female guinea-pigs were found to have reproductive tract leiomyomas at necropsy. Sixty-three of these guinea-pigs also had cystic rete ovarii. Eleven separate leiomyomas were identified, the most common site of formation being the uterine body or horn. The tumours contained histological evidence of smooth muscle, abundant fibrous connective tissue and occasional foci of fibrocartilage and bone. Mitotic figures were identified in only one tumour. The mean age of guinea-pigs with leiomyomas was 47·6 months, and the mean age of the study population was 33·1 months. Two other reproductive tract tumours identified in the 83 guinea-pigs were an ovarian teratoma and a cavernous haemangioma. These data indicate that leiomyomas are the most common reproductive tract tumour in this colony of aged female guinea-pigs and that they are frequently seen in conjunction with cystic rete ovarii.

Fall in the number of myenteric neurons in aging guinea pigs

The neurons of the myenteric plexus of the entire small intestine were stained in young adult (3–4 mo old) and aging guinea pigs (26–30 mo old). Total length and circumference of the intestine were measured in the same experiments. The small intestine of the aging guinea pigs was longer, and (in the conditions of distention used) had a total serosal surface ~70% greater than in young adult animals. The spatial density of myenteric neurons per unit of serosal surface fell dramatically in aging animals, and the total number of myenteric neurons in the small intestine ranged between 1.1 and 1.6 million, i.e., it was only 40%–60% of the value obtained in young adult guinea pigs (2.75 million). The light microscope appearance of the neurons of the two groups of animals was markedly different and the suggestion is put forward that in aging guinea pigs the substantial reduction in neuron number is accompanied by structural changes and reorganization of the neurons that are left.

Relationship between Dietary Intake and Tissue Levels of Reduced and Total Vitamin C in the Nonscorbutic Guinea Pig

The objective of this study was to determine the effect of a broad range of dietary intake levels of ascorbate on the distribution of both total and reduced ascorbate in guinea pig tissues. Young male Hartley guinea pigs were fed for 2 mo a modified Reid-Briggs purified diet containing five different levels of total ascorbate that provided 0.8-52 mg ascorbate/d. We also fed aged guinea pigs two different levels of ascorbic acid (1.5 or 60 mg/d) for 2 mo. Reduced and total ascorbate was measured in eye lens and aqueous humor, liver, kidney and plasma. The data indicate that it is possible to markedly enhance the level of ascorbate in tissues above that obtained by feeding a diet that contains only enough ascorbate to prevent scurvy. In all tissues, as the level of total ascorbate present in the tissue increased, so did the proportion present in the reduced form. In old guinea pigs, the eye lens was the only tissue in which both reduced and total ascorbate were significantly lower than in the young guinea pigs at both high and low intake levels.

The effect of aging on cutaneous lipid peroxide levels and superoxide dismutase activity in guinea pigs and patients with burns

Cutaneous lipid peroxide levels and superoxide dismutase (SOD) activity in non-aged and aged guinea pigs were measured between 15 min and 7 days after experimental infliction of burns. Skin burns on non-aged and aged patients were also subjected to these assays. In non-aged guinea pig skin burns, lipid peroxide levels increased from 24 hr to the fourth day after the burn infliction, shile SOD activity did not increase but showed a slight decrease 12 hr and 24 hr post-burn. On the other hand, while the aged group showed a more increase in skin lipid peroxide levels compared to that seen in non-aged mice, skin SOD activity began to decrease from 30 min post-burn, the maximum decrease being reached on the second day. The activity did not return to normal by the 7rh day. In non-aged patients skin burns showed increases in both lipid peroxide levels and SOD activity, while in aged patients, though they showed a marked increase in lipid peroxide levels, SOD activity remained unchanged. The present study indicated that, although in our recent study, skin SOD activity of healthy elderly people was found to be comparable to that in non-aged individuals, the capacity for induction of SOD activity under oxygen stress differed with age in both guinea pig and human burn sufferers. Furthermore, this induction capacity seemed to vary from species to species.

Age associated increase of C cell follicles in guinea pig thyroid glands.

The effect of aging on the formation of C cell follicles was examined in the thyroid gland of guinea pigs at various ages ranging from 1 to 29 months. The C cell follicles were demonstrated with the immunoperoxidase methods by using anticalcitonin and antisomatostatin antisera and with PAS reaction. They were already detected in 1-month-old guinea pigs but in low number. Thyroid glands from 1- to 14-month-old animals contained only a small number of C cell follicles and did not reveal the age-related increase. In aged guinea pigs (20- to 29-month-old), a dramatic increase of C cell follicles was found, about 13 times as high as the number of other age groups. The C cell follicles through all age groups were present in large clusters of C cells. In the aged guinea pigs, nodular large aggregates of C cells regarded as C cell hyperplasia occurred and numerous C cell follicles were formed in the large cell aggregates. Thus, the conspicuous increase of C cell follicles in aged animals was associated with a proliferative abnormality of C cells. The C cells forming follicles showed moderate to weak immunoreactivity for calcitonin, whereas they showed very intense immunoreactivity for somatostatin. In addition, the colloidlike and flocculent materials stored in the follicular lumina, which were consistently PAS-positive, were weakly immunoreactive to somatostatin but nonreactive to calcitonin.

Impaired T-cell functions in aged guinea-pigs restored by Thymostimulin (TS)

The age-related changes of different T-cell activities in guinea pigs and the effect of Thymostimulin (TS), a thymus extract, on the immunocompetence of these cells was studied. Mitogen-induced proliferation of peripheral blood lymphocytes was increased by TS in vitro. The intraperitoneal administration of TS (5 mg/kg) to aged animals restored the helper function of T lymphocytes and enhanced the reactivity to mitogens of both peripheral blood lymphocytes and spleen lymphocytes. The data obtained suggest that as in other species, there is an age-associated decline of immunological response, in guinea pigs too, probably due to a deficiency of thymic hormone(s) and that TS could correct this deficiency.

Serous cysts of the aging guinea pig ovary. III. Permeability of the cyst epithelium to lanthanum and horseradish peroxidase.

The permeability of the epithelium lining serous cysts of the guinea pig ovary was examined using lanthanum and horseradish peroxidase (HRP). Both lanthanum and HRP introduced at the luminal surface of the cyst penetrated to the basal region filling caveolae in both lateral and basal cell surfaces. Within three minutes of vascular infusion of HRP, the tracer was detected between epithelial cells and in caveolae on their lateral and basal surfaces but not associated with intracellular organelles. There was no change in the intracellular distribution of HRP after ten minutes. It was concluded that the epithelium was permeable to the tracers within this time period but that pinocytosis and transport of these tracers through the epithelial cell were not demonstrated.

Effect of a thymic factor (TS') on the immune response of aged guinea pigs

Effect of a thymic factor (TS') on the immune response of aged guinea pigs

MORPHOLOGICAL CHANGES OF THE MUSCLES AND MOTOR END-PLATES OF CENTROPHENOXINETREATED AGED GUINEA PIGS

Centrophenoxine, 80 mg/kg/day, was administered to 25-month old guinea pigs intraperitoneally for 90 or 127 days and the muscles and motor end-plates were examined histochemically. The results showed some improvement of muscle atrophy and deformity of the motor end-plates in the aged guinea pigs. However, it is not clear whether these changes result from the central action or the peripheral action of centrophenoxine.

Serous cysts of the aging guinea pig ovary. II. Scanning and transmission electron microscopy

Ovarian cysts which developed spontaneously from the rete ovarii in the ovaries of guinea pigs have been examined in 1- and 2-year-old animals by scanning and transmission electron microscopy. Two cell types have been described, a tufted cell with numerous motile cilia and a non-tufted cell with a solitary cilium. While the non-tufted cell exhibited numerous smooth coated vesicles in its lateral and basal regions, no signs of secretion to the lumen of the cyst have been seen and occluding junctions have not been observed.

Serous cysts of the aging guinea pig ovary. I. Light microscopy and origin.

Ovaries from guinea pigs of different ages have been examined by light microscopy. Serous cysts measuring between 1 mm and 2.5 cm are present in all animals over one year of age. The cysts are fewer in number and size at six months, are least developed at ten weeks and are not apparent in the near-term fetus. The cysts arise from the rete ovarii. They are lined with a simple cuboidal to columnar epithelium composed of cells bearing solitary cilia or tufts of cilia. The structure and origin of these cysts is discussed and compared with what is known of the human serous cystadenoma.

Macrophage Heterogeneity in Receptor Activity: The Activation of Macrophage Fc Receptor Function in Vivo and in Vitro

The Fc receptor activity of single macrophages and of distinct macrophage populations was examined in terms of cellular avidity for IgG antibody by using a rosette assay which permits characterization of receptor activity at the cellular level and quantitation of any changes in such receptor activity. Marked heterogeneity was shown to exist within normal populations of macrophages. Both normal peritoneal and alveolar macrophage populations exhibit a normal or logistic distribution of cellular avidities for IgG antibody. The mean avidity of the peritoneal population, however, was found to be approximately 3 times greater than that of the alveolar population. Moreover, alveolar macrophages possess a range of cellular avidities 3 times greater than that of peritoneal macrophages. Comparison of normal unstimulated peritoneal macrophages and induced inflammatory exudate macrophages revealed a 6-fold increase in the proportion of high avidity cells in the latter population. Normal peritoneal and normal alveolar macrophages were shown to undergo a striking increase in Fc receptor activity in vitro. Under certain conditions of culture these cells acquire the antibody-binding capacity characteristic of high avidity cells in the inflammatory exudate population. Fresh guinea pig serum was shown to prevent this activation of Fc receptor function in vitro. Aged guinea pig serum was somewhat less effective. The serum factor(s) responsible appears to be consumed or exhausted in some way by macrophages. It is heat stable and has a molecular weight of less than 100,000 daltons. Serum IgF was found not to be involved in the effects of fresh serum on receptor activation in vitro. The activation of Fc receptor function described here may facilitate both the presentation of antigen to specific T lymphocytes and the antibody dependent killing of tumor cells by macrophages. Changes in receptor activity of the kind described may thus play an important regulatory role in the induction of an immune response and in the effector mechanisms of immunologic surveillance.

Direct hemadsorption by cell cultures infected with rubella virus.

SINCE the demonstration by Shelokov et al1of hemadsorption of myxovirus infected cell cultures, this phenomenon has been used for the isolation and study of a variety of hemagglutinating viruses. Although rubella virus has been shown to possess hemagglutinating activity,2the adherence of erythrocytes to cell cultures infected by rubella virus has not been previously described. In contrast, there have been reports suggesting the opposite. Infection by rubella virus has been shown to inhibit nonspecific tissue hemadsorption of aged guinea pig erythrocytes on a continuous cell culture of rabbit kidney,3and the interference of rubella virus with superinfection by Newcastle disease virus has been demonstrated by hemadsorption-negative areas on the cell culture.4While the exact classification of rubella virus is still being debated, notable similarities exist between the growth characteristics, morphology, and hemagglutinating properties of rubella virus and various arboviruses.5The finding of virus-specific hemadsorption