Brief occlusion of the main pancreatic duct rapidly initiates signals which lead to increased duct cell proliferation in the rat.

In the course of investigating the signals associated with pancreas regeneration, we have developed a method to initiate pancreatic duct cell proliferation by brief occlusion of the main pancreatic duct. The resulting duct cell proliferation, induced by temporary partial main duct occlusion, was compared to that induced by firmly tying a cellophane strip around the head of the pancreas for longer periods of time. Both methods stimulated a biphasic increase in duct cell proliferation, with proliferation maxima at 3 and 14 days post operation. The short duration of temporary main duct occlusion (60 s) that was needed to stimulate duct cell proliferation, and the similar duct cell proliferation profiles that were observed after both the temporary and the longer term main duct occlusion, led us to conclude that the signals which initiate proliferation occur rapidly at the beginning of each procedure.

Development, differentiation, and regeneration potential of the Vervet monkey endocrine pancreas.

Using immunolabelling techniques, characterization of the Vervet monkey pancreas included a study of both its development and its structure and normal functioning in the adult. We found that PP and somatostatin occurred during development before glucagon. Insulin and all four pancreatic peptides occurred in one of the primordial buds prior to fusion. These finding call into question the suggested contribution of only PP cells by the ventral bud and non-PP cells by the dorsal bud. Co-localization of glucagon and PP was observed extensively with their relative expressions occurring in what appeared to be an organised non-random manner. Cells expressing both glucagon and PP persisted in the adult, together with many other combinations, suggesting an interesting plasticity of endocrine cell differentiation in the adult. Cellophane wrapping of the head of the Vervet monkey pancreas was shown to result in a noticeable increase in duct cell proliferation and endocrine cell volume but no increased replication of endocrine cells. Cells, immunoreactive for pancreatic peptides, were observed to bud from the ducts, suggesting a regeneration of endocrine cell tissue by neogenesis, although it is uncertain whether the duct epithelium contains the only stem cell source of new endocrine tissue. Hopefully, further investigations will elucidate a mechanism by which endocrine cell regenerative capacity can be stimulated in diabetics to overcome their absolute or relative deficiencies of insulin production.

Induction of cell proliferation and differentiation in the pancreas of the adult Vervet monkey (Cercopithecus aethiops): preliminary results.

Cellophane wrapping of the adult Syrian golden hamster pancreas has been found to result in ductular cell proliferation leading to islet regeneration. Injection of cytosol from a cellophane-wrapped pancreas into normal or diabetic hamsters evoked a similar response. In view of the therapeutic potential of the active substance in this cytosol, it was decided to investigate whether a similar response could be achieved in a primate. In normal adult Vervet monkey (Cercopithecus aethiops) pancreas, proliferation is seen only rarely in islet cells and occasionally in duct and acinar cells. Immunohistochemical investigation of normal Vervet monkey pancreas (n = 4) and 14 days (n = 2) and 56 days (n = 1) after cellophane wrapping of the Vervet monkey pancreas revealed a slight increase in proliferation of islet and acinar cells and a larger increase in proliferation of duct cells and in total endocrine cell volume. The results suggest that there is a latent developmental capability in the adult primate pancreas.

Distribution of endocrine cells displaying immunoreactivity for one or more peptides in the pancreas of the adult vervet monkey (Cercopithecus aethiops).

BACKGROUND: Our previous studies on the Chacma baboon revealed that the most striking difference between islets of the ventral and dorsal regions of the pancreas was their content of A and pancreatic polypeptide (PP) cells with A cells predominating in the tail and PP cells in the uncinate and head. Cells displaying dual immunoreactivity for both glucagon and PP were also observed. The objective of this study was to establish baseline parameters of the adult Vervet monkey (Cercopithecus aethiops) pancreas so that it could be used as a primate model to investigate possible therapies for diabetes. METHODS: Vervet-monkey pancreas was divided into uncinate, head, and tail regions, and the tissue processed for immunolabelling for pancreatic peptides using avidin-biotin-peroxidase as marker. Dot-blotting and absorption controls for antibody specificity were included because of the shared amino acid sequences in pancreatic polypeptide (PP), neuropeptide Y (NPY), and peptide YY (PYY). Endocrine cell distributions and the percentages of each cell type per region were calculated for each monkey. RESULTS: A significant difference in the percentages of PP cells (P = 0.02) was observed between uncinate and tail regions, the distribution of NPY cells was similar to that of the PP cells, and all other distributions were similar to those reported in the literature for most animals studied. Cells displaying dual immunoreactivity for glucagon and PP or NPY, PYY and NPY, or PP, PP and somatostatin and glucagon and insulin were identified and mapped throughout the pancreas. Most co-localizations occurred in the uncinate region. Co-localization of glucagon and insulin has not, to our knowledge, been reported previously in the adult pancreas. CONCLUSIONS: Pancreatic endocrine cell distribution in the adult Vervet monkey was found to be very similar to most other animals studied. The occurrence of cells displaying dual immunoreactivity for a number of different combinations of pancreatic peptides suggests an interesting plasticity of endocrine cells even in the adult animal.

The effect of diet on the Vervet monkey endocrine pancreas.

Vervet monkeys (Cercopithecus aethiops) used for pancreatic endocrine cell distribution studies were found to have been maintained on different diets. Although the effect of dietary changes on the exocrine pancreas has been described in several animals, little, apart from the effect of malnutrition, has been reported for the endocrine pancreas. Reported here are pancreatic endocrine cell distributions in monkeys on a standard diet (n = 3) compared with monkeys on an atherogenic diet (n = 3). Quantitation of immunolabelled pancreatic endocrine cell types revealed a significant 80% increase in A (glucagon) cell volume in monkeys on an atherogenic diet concomitant with a significant reduction in B (insulin) cell volume to approximately 60% of normal. This reflects a pattern of events that occurs in non-insulin dependent diabetes. An accompanying reduction in PP (pancreatic polypeptide) cell volumes supports our hypothesis that altering A and PP cell volumes could reflect differential gene expression in those cells in the adult in which glucagon and PP are co-localized.

The non-human primate endocrine pancreas: development, regeneration potential and metaplasia.

An investigation into the development of the Vervet monkey endocrine pancreas revealed a sequence of occurrence of pancreatic peptides that differed from previous reports in mice, dog and human with PP and somatostatin occurring before glucagon and insulin. All four pancreatic peptides were identified, immunohistochemically, in only one of the pancreatic primordial buds, before fusion of the two buds to form the pancreas. This questions the hypothesis that the heterogeneous endocrine cell distribution seen in the adult pancreas is due to the contribution of only PP cells by the ventral bud and non-PP cells by the dorsal bud. Co-localization of glucagon and PP was observed extensively in the developing pancreas and the predominant expression of one over the other in an apparently organized non-random manner accounted for the glucagon- and PP-rich areas seen in the developing pancreas. A small number of cells immunoreactive to glucagon and PP were also observed in the adult. Reports of plasticity of differentiation of other pancreatic cells led us to investigate regeneration potential of the adult monkey pancreas. Partial obstruction of the Vervet monkey main pancreatic duct, by cellophane wrapping, resulted in duct cell proliferation and differentiation to form new endocrine tissue in a way that mimics normal organogenesis. Focal areas of hepatocytes were found in the regenerated pancreas of one monkey, illustrating further the latent developmental capabilities of adult pancreas cells. These findings could lead to interesting new therapies for pancreas and liver disease.

Pleural Mesocestoides and cardiac shock in an obese vervet monkey (Cercopithecus aethiops).

Only one case of infection by tetrathyridia larvae of the tapeworm genus Mesocestoides was detected in 416 necropsies of captive vervet monkeys (Cercopithecus aethiops). Two hundred nine larvae were distributed between both pleural cavities. Mass and size ranges of larvae were determined. A plasma cell reaction indicated a humoral immune response to parasite antigens, which may have contributed to acute, lethal cardiac shock. Coagulative myocytolysis was confirmed. The history of this case and associated circumstantial evidence and reports in the literature suggest that infection of primates by tetrathyridia probably occurs after capture rather than before.

Mycotoxic peripheral myelinopathy, myopathy, and hepatitis caused by Diplodia maydis in vervet monkeys.

During recent historical times many Africans changed their diet to one based on maize. The grain is regularly contaminated by fungi which are toxigenic to domestic animals and birds. After one of the fungi, Diplodia maydis, in pure culture on maize, was added to the food of omnivorous primates there was demyelination of nerves, atrophy, degeneration and necrosis of muscle, and hepatitis. These preliminary results are applicable to veterinary and laboratory animal sciences. They may also be medically significant since neuromuscular syndromes of unknown cause are prevalent among Africans. Nerve conduction velocities and organ weights are defined for vervet monkeys.

Atherosclerosis. Chronic effects of fish oil and a therapeutic diet in nonhuman primates.

Prolonged testing of marine fish oil (FO) as a dietary supplement is necessary because of widespread claims that it is antiatherogenic. The basis for such claims is inadequate because atherogenesis is chronic and may not respond to short-term changes induced by dietary treatments. A proven (vervet) model of atherosclerosis promoted by an atherogenic diet (AD) was used to test dietary supplementation with Atlantic pilchard FO for 20 months in 47 omnivorous nonhuman primates. Responses were controlled against known favorable effects of changing from the AD to a therapeutic diet (TD). Compliance was achieved, and tissue responses to the FO dose were confirmed. Compromise of reflex vasoconstriction by atherosclerosis was demonstrated for the first time in the model. Aortic, peripheral, coronary, and cerebral atherosclerosis were assessed by light microscopy and computerized image analysis. No component of atherosclerosis regressed after dietary FO, and several deteriorated. After a change to the TD, stainable lipid was cleared from aortas and there were few lipophages, but advanced atherosclerosis was not reduced. Male vervets developed more severe atherosclerosis than did females, and the association among aortic, peripheral, and coronary atherosclerosis was positive in males. Females were resistant to coronary atherosclerosis. Only mild cerebral atherosclerosis was detected. In conclusion, the FO used was not antiatherogenic in the model, and there is a need for caution. The TD regresses some components of atherosclerosis, but it was not effective against fibrosis, mineralization, and cholesterol crystals within 20 months.

Oesophageal mucosal pathology in a population at risk for gastric and oesophageal carcinoma.

Statistical studies of oesophageal and gastric carcinoma at Groote Schuur Hospital during a 4 year period and a detailed pathological assessment of oesophageal mucosal biopsies of 526 rural outpatients are reported. A statistically suggested high incidence of oesophageal carcinoma was confirmed by endoscopical studies. Oesophageal carcinoma was detected endoscopically in 1.14% of patients with dyspepsia. Oesophagitis and glycogenic acanthosis were common findings which were related to smoking and alcohol intake, but were not related to cancer risk. Precursor lesions for oesophageal carcinoma are discussed.

The association of Campylobacter pylori with mucosal pathological changes in a population at risk for gastric cancer.

In the study of a group of 178 unselected patients (105 men, 73 women, mean age 44.5 years), from a population at high risk for gastric carcinoma, who presented with chronic dyspepsia, a minimum of 8 gastric and oesophageal biopsy specimens were taken during upper gastro-intestinal endoscopy, and examined histologically and histochemically for the presence of Campylobacter pylori and other pathological lesions. Gastric colonisation by C. pylori was found in 75% of men and 68.4% of women. In 90% of patients with duodenal or gastric ulcer and in 71.6% of patients with non-ulcer and non-cancer dyspepsia there was a moderate or severe degree of bacterial colonisation. Association between C. pylori colonisation and microscopic evidence of type B gastritis, gastric or duodenal ulcer, gastric cancer, oesophagitis and oesophageal glycogenic acanthosis was found.

Promotion and regression of atherosclerosis in vervet monkeys by diets realistic for westernized people.

We have described and measured aortic and arterial atherosclerosis in adult female Vervet monkeys (n = 61) after application of dietary treatments for 47 months. The diets were compounded entirely of normal food items for westernized people, with no extra cholesterol added. A 'Western' diet (WD), known to induce hypercholesterolaemia, was found to be atherogenic in aortas and some arteries. A more 'prudent' diet (PD) induced much less lipid infiltration into aortic intimas and was not associated with serious atherosclerotic changes. However, when this PD was used as a treatment for 27 months, following 20 months of nutrition by the WD, minimal regression of cholesterol crystals and non-lipid components of atherosclerotic plaque was detected. There was no significant coronary artery or myocardial disease in these adult females after 47 months of feeding on the WD whereas males do develop coronary atherosclerosis and myocardial fibrosis. For this model the PD would be more effective in preventing atherosclerosis than treating advanced lesions. We believe this is the first time that the pathology of atherosclerosis promoted by realistic diets has been modelled in adult females of this species.

The histology and carbohydrate histochemistry of the lingual glands in vervet monkeys.

The lingual salivary glands of the vervet monkey were examined for the first time to establish their histological appearance and mucosubstance histochemistry. Sero-mucous and mucous glands are present. The mucin content of the serous glands is a neutral mucin, that of the mucus glands a carboxylated or sulphated sialomucin. The reason for the variation between cells was not established. Anterior lingual glands were not detected in any of the tongues examined.

The influence of diet and dimethylhydrazine on the small and large intestine of vervet monkeys.

The morphological features of the intestine in monkeys on various diets with and without carcinogen were studied. Seventy adult female vervet monkeys were divided into seven treatment groups. Four groups received a Western high-fat low fibre diet (WD); two a Prudent low-fat higher fibre diet (PD) and one a control low-fat high fibre diet (CD). Three groups (2 WD, I PD) received dimethylhydrazine 10 mg/kg intramuscularly at 14 days intervals. After 18 months, monkeys of two groups on the WD were transferred to the PD and 30 months later all were terminated. Small and large intestine were examined macroscopically, histologically with morphometry, histochemically for acid and neutral, sialo- and sulphomucins and enzyme-histochemically for mucosal gamma-glutamyltranspeptidase (GGT) activity. Large intestines in all other than CD, particularly in WD-treated animals were dilated, thin walled, less corrugated and contained more residual contents. Diverticulosis was found to be mostly associated with WD. Apparently histologically normal colonic mucosa showed changed mucin secretion, predominantly in WD groups, and also GGT activity in all but CD groups. Changes which could be associated with pre-malignancy occurred predominantly but not exclusively in carcinogen treated animals. Within 4 years of feeding to monkeys, diets used by affluent western man caused distinct changes suggestive of the development of intestinal diseases such as megacolon, diverticulosis and cancer. Feeding a prudent diet resulted in only a mild reduction of these signs, whereas they were absent in a usual monkey diet that was much lower in animal products and refined carbohydrates.