A scanning electron microscopic morphological and semi-quantitative evaluation of rat stomach treated with colloidal bismuth subcitrate and alcohol.

Scanning electron microscopy was utilised to study the effect of absolute alcohol on the normal morphology of the rat stomach, together with the gastroprotective actions of colloidal bismuth subcitrate. Studies on normal gastric morphology revealed that the major portion of the stomach was covered by a protective coating of mucus. However, there was considerable variation in the integrity of the mucosal surface of the control animals, with the loss of surface epithelial cells in some regions which may account for the variation in response to necrotising agents. The long-term administration of the gastrocytoprotective agent colloidal bismuth subcitrate resulted in a marked improvement in normal gastric integrity, compared with control tissue samples. The administration of absolute alcohol was associated with an excessive production of mucus and caused extensive damage to the gastric mucosa of control animals, resulting in destruction of the surface epithelial cells and exposure of the reticular framework. However, there was evidence that repair of this damage was underway by four hours after ethanol treatment, with a significant degree of recovery from damage occurring by 24 hours after treatment. In contrast, treatment with colloidal bismuth subcitrate prior to the administration of alcohol resulted in a significant reduction in the degree of damage induced by alcohol administration, suggesting that colloidal bismuth subcitrate has the ability to protect the stomach from the erosive action of alcohol.

Effect of colloidal bismuth subcitrate on age related gastric lesions in the rat.

The purpose of this study was to determine the changes in rat gastric functional morphology that take place with age and to study the action of colloidal bismuth subcitrate on the age related degeneration of the stomach. At 95 weeks of age erosions were apparent over 80% of the gastric mucosa and this was associated with a significant decline in the numbers and mucus content of the mucosal epithelial cells. The rate of stem cell proliferation in the neck region was also significantly lower than that found in 9 week old animals. The administration of 50 mg/kg colloidal bismuth subcitrate for 14 days to 9 week old animals resulted in slight hypertrophy of the mucosal epithelial cells. When 95 week animals were placed on the same regimen there was a decline in the number of deep erosions in the mucosa and an increase in the number and mucin content of the mucosal epithelial cells. A significant increase in the proliferation of the stem cell population was also observed after colloidal bismuth subcitrate administration. It is suggested that colloidal bismuth subcitrate may ameliorate the increased susceptibility to harmful agents that occurs with age.

Effect of repeated colloidal bismuth subcitrate treatment on the response of the rat gastric mucosa to the presence of luminal ethanol.

The purpose of this study was to determine the effects of repeated colloidal bismuth subcitrate administration on the cellular populations of the fundic region of the rat stomach and to investigate the effect of such treatment, after initial ethanol damage, on the gastric response to a second challenge by ethanol. The administration of 240 mg of colloidal bismuth subcitrate per kilogram body weight, at 12 hour intervals, for 14 days, resulted in an increase in the density of the mucosal epithelial cells, but a decreased rate of epithelial cell division in the neck region. Comparison with placebo treated animals showed that the repeated administration of colloidal bismuth subcitrate after an initial ethanol challenge, decreased the degree of damage induced by a second ethanol challenge, enhanced the rate of tissue repair and prevented the establishment of persistent erosions.

Determination of extracellular pH and tissue temperature in transplantable rat tumors by use of inductive loop telemetry.

Radiotelemetry was used to determine changes in extracellular pH and tissue temperature during tumor development in rats of an inbred WAB substrain. A progressive decrease in the pH of the tumor tissue compared with the pH level in control tissue was observed, so that by 4 days after tumor implantation the tumor tissue was about 0.4 pH units lower than control values. Thereafter, tumor pH rose progressively to reach a value comparable with control levels at 8 days, when the experiment was terminated. No significant difference was detected between the temperature in the tumor tissue and the temperature in the control tissue. Therefore, the observed changes in pH appeared to be independent of temperature. Studies on the rate of tumor cell proliferation during the experiments demonstrated a significant inverse relationship between tumor cell mitotic rate and pH, with the highest rates of cell proliferation occurring at the time of lowest pH values.

The effect of dietary restriction on thymus autonomy.

Fifty percent dietary restriction allows for continued body growth in young animals, whereas in older animals this dietary regime resulted in a 25% drop in body weight over a 10-wk period. This resulted in a relatively low rate of mitosis in the thymus tissue from young animals so that thymus size was maintained in proportion with body weight. There was no evidence to suggest that the thymus glands from dietary restricted young animals could not maintain their role in immune function. In the older animals dietary restriction resulted in depletion of thymic lymphocytes, despite a relatively high rate of cell division. It is postulated that this may be a result of stress caused by the dietary regime.

An accurate, long-term, pH-sensitive radio pill for ingestion and implantation.

The design of a new radiotelemetry capsule (26 mm long X 7.6 mm diameter), with an in vivo life of 1 month is described in the context of previous work in this field. In vitro evaluation of the capsule indicates an accuracy and performance comparable with a conventional pH meter. Several clinical applications are described, including measurements of gastrointestinal pH in humans and the measurement of extracellular pH in laboratory animals.

Influence of lodgement site on the proliferation of metastases of Walker 256 carcinoma in the rat.

The growth of s.c. Walker 256 carcinoma was found to be independent of secondary growths induced by i.v. injection. Tumour cells injected i.v. lodged mainly in the lungs, with small clusters of cells in the lymph nodes. The rate of cellular proliferation of these secondary growths of Walker carcinoma was significantly higher than that observed in the s.c. tumour. In addition, host lung tissue was found to inhibit the development of metastases, and it is postulated that the host tissue may produce a diffusible inhibitor and that differences in the effectiveness of these humoral factors may account, in part, for locational differences in tumour growth patterns.

Density-dependent cell division after cortisol treatment of rat thymus in relation to age involution.

Cellular proliferation, in relation to cell density was investigated in the thymus of control and cortisol treated animals at 6 and 18 weeks of age. It was found that there was very little difference in the response of the two age groups to cortisol treatment. Cell density and cellular proliferation were markedly reduced 2 days after cortisol administration. From 4 days there was a rapid increase in cellular proliferation to triple the control rate. The mitotic index remained above normal until 12days then decreased to control values at 14 days. During this time the cell density of the thymus was being progressively restored. At all stages of regeneration, the mitotic index at first increased to a maximum at the mean cell density then decreased at the highest cell concentrations. A model system is discussed to account for this density dependent control of cellular proliferation in the thymus.

Spontaneous thymoma in an inbred strain of rat.

Thymomas that appear with high frequency in inbred WAB rats living into old age were examined. The spontaneous thymomas described were discrete, encapsulated bodies composed of lymphocytes and epithelial cells, with a predominance of lymphocytes. The rat neoplasms resembled the human thymomas, and their rate of incidence in older animals may suggest their use as models for the human condition.

A quantitative histological assessment of cellular death, in relation to mitosis, in rat thymus during growth and age involution.

The rates of cellular proliferation and cellular death were investigated in the rat thymus during growth and involution. It was found that the percentage of dead cells gradually increased with age, whilst the rate of cell proliferation declined, indicating that a substantial proportion of lymphocytes that divide in the thymus also die there. It was also found that there exists a density-dependent distribution pattern of mitotic and dead cells and that this distribution pattern changed with age. It is suggested that this mechanism of density-dependent control of the thymus may be an important factor in the age involution of the thymus.

Factors controlling growth and age involution of the rat thymus.

Thymic development and somatic growth were investigated in three strains of rat. The well established influence of sex and age on somatic growth was confirmed. It was also found that the rate of thymic growth was not influenced by the sex of the animal until four weeks of age, but thereafter, the thymus grew faster in males compared with females of the same strain. Gonadectomy had a marked effect on the thymus, resulting in a higher rate of growth than in normal animals; but a slower initial rate of involution. The maximum thymus weights attained in gonadectomized animals were found to be independent of the age at which the animals were gonadectomized or of the sex of the animal. Gonadectomy did not influence the point at which involution began. Thymic mitotic indices of gonadectomized animals were found to be higher than those of normal animals. The influence of sex hormones on somatic growth and the development of the thymus is discussed, and it is concluded that cell loss is the regulator of thumus growth and involution.

On the role of the reticular-epithelial complex in transplantation of the thymus.

Transplantation of the neonatal thymus, into young, adult hosts, resulted in massive cell death of graft cortical lymphoid tissue with apparent selective survival of the reticular-epithelial cells. The central area of the graft was progressively cleared of cell debris and the characteristic thymic architecture restored within fourteen days of grafting. Evidence obtained from the regeneration of different-sized transplants suggested that the size and shape attained by the regenerated graft was closely related to the size and shape of the donor tissue. When donor rat thymuses were transplanted in Millipore chambers, the lymphocyte population did not reappear and after seven days only reticular-epithelial cells remained, retaining their normal appearance. However, when these thymic remnants were removed from the chambers and transplanted into secondary hosts, the thymus regenerated normally, suggesting that the lymphocytes in the regenerated gland were derived from the host. Thymic remnants after cortisol treatment of donors also formed distinct organs after grafting despite the fact that they contained few donor lymphocytes. From the differential effects of cortisol on host and transplanted thymus and the different growth characteristics of transplants it appears that transplants differ in their growth/involution control system from the host thymus.