Dose-dependent pancreatotrophic effect of cholecystokinin-octapeptide in the rat: the influence of starvation.

Cholecystokinin (CCK) and its analogues are known to exert trophic effects on the exocrine pancreas, whereas at high doses, they produce pancreatic injury. This study was carried out to study the effect of starvation on the dose-dependent pancreatotrophic effect of CCK-8 in rats. Normal or fasted rats were treated with CCK-8 doses ranging from 0.5 to 32 and 0.5 to 8 micrograms kg-1, respectively, twice daily for 5 days. Pancreatic size, protein, DNA, secretory enzyme and trypsin inhibitor (PSTI) contents as well as histology were examined. In normal rats, CCK-8 increased the pancreatic content of protein, amylase, serine proteases and PSTI with maximum values between doses of 2 and 16 micrograms kg-1. The dose of 32 micrograms kg-1, however, yielded less trophic responses. Given to fasted rats, CCK-8 increased the weight as well as protein and secretory enzyme contents of the pancreas with maximum values between doses of 1 and 4 micrograms kg-1. The first dose supramaximum for the trophic responses was as low as 8 micrograms kg-1. Histology revealed necroinflammatory damage (acinar cell vacuolization, focal cell necrosis) in the exocrine pancreas at supramaximum doses of CCK-8 in both groups. Cell necroses and vacuolization were less but present even at doses optimum for trophism and exhibited dependence on both the dose of CCK-8 and nutrition. In either the normal or fasted animals, the periinsular acini were relatively less affected by the toxic effects of CCK-8 than the teleinsular ones. The results indicate that starvation makes the exocrine pancreas more sensitive to necroinflammatory effects of CCK-8. The relative protection seen in periinsular acini suggests a modulatory influence of islet hormones on development of CCK-induced acinar cell injury.

One-year treatment with cholecystokinin-octapeptide and secretin: effects on pancreatic trophism in the rat.

The effects of long-term administration of cholecystokinin octapeptide (CCK-8) with or without secretin on the pancreas were examined in groups of rats treated with: (1) CCK-8 (1 microgram kg-1); (2) secretin + CCK-8 (1 microgram kg-1 of each); or (3) saline, administered subcutaneously twice daily for 5 out of 7 days for 6 or 12 months. A number of rats from all groups were studied for: (1) pancreatic size and biochemical composition (n = 6 for each group); (2) pancreatic secretion in the anesthetized state (n = 5 for each group); and (3) pancreatic histology (n = 6 for each group) after a 6-month treatment period. The rest of the animals treated for an additional 6-month period (n = 13 for each group) were examined for pancreatic size and histology. CCK-8 increased the weight of the pancreas and its contents of DNA, protein, trypsinogen, chymotrypsinogen, proelastase, secretory trypsin inhibitor and amylase, but not that of lipase when given for 6 months, whereas administration of secretin + CCK-8 doubled the pancreatic content of lipase and increased all trophic parameters (except the amylase content) over those of CCK-8-treated rats. Maximum pancreatic volume and protein outputs in response to CCK-8 were higher in both of the hormone-treated groups than in the control; the sensitivity to the secretory action of CCK-8 was not altered. Pancreatic mass increased in response to either treatment after 12 months as well. Histological examination did not reveal pancreatic neoplasia in either group. The results indicate that long-term administration of CCK-8 or secretin + CCK-8 in rats results in sustained pancreatic hypertrophy and hyperplasia with secretory hyperfunction with no evidence of neoplastic alterations.

Pancreatic trophism in experimental liver cirrhosis.

Pancreatic trophism and pancreatic enzyme composition, and plasma levels of cholecystokinin, insulin, glucagon, and glucose in liver cirrhosis induced by chronic thioacetamide administration (0.02% in the drinking water for 12 mo) were studied in rats. Advanced liver cirrhosis was evident in all thioacetamide-treated rats. The weight of the pancreas and its contents of DNA, protein, trypsinogen, chymotrypsinogen, proelastase, secretory trypsin inhibitor, and amylase were significantly increased as compared to the controls. The pancreatic secretory enzyme content changes showed a nonparallelism, characteristic of a cholecystokinin effect. Light and electron microscopy revealed a normal pancreatic architecture. Bioassayed plasma cholecystokinin levels in both fed and 24-h-fasted cirrhotic rats were significantly higher than in the corresponding controls. The plasma glucose, insulin, and glucagon levels demonstrated hypoglycemic tendencies with a glucagon predominance. These findings indicate that advanced liver cirrhosis in the rat is accompanied by pancreatic hypertrophy and hyperplasia, which might be attributed, at least in part, to elevated circulating cholecystokinin levels.

Proteinuria in the bovine serum albumin loaded rats is aggravated by genetically determined hypertension.

The effects of bovine serum albumin (BSA) loading on urinary protein excretion rate (PU) were investigated in spontaneously hypertensive (Okamoto) and normotensive Wistar-Kyoto and Wistar rats. Baseline PU was greater in spontaneously hypertensive rats of both sexes than in the corresponding normotensive groups. Male rats excreted more protein than females. A significant direct correlation could be demonstrated between blood pressure and PU induced by BSA. Glomerular epithelial cell foot process fusion rate was significantly greater in female spontaneously hypertensive rats than in all other groups and correlated with PU increase, especially in female spontaneously hypertensive rats. This study therefore indicates that hypertension which is acquired independently of the glomerular lesion induced by BSA administration accentuates proteinuria in this model of disease.

[Simultaneous occurrence of persistent hematuria (thin basement membrane nephropathy) and light-chain proteinuria (benign monoclonal gammopathy) in a middle-aged male]. / Persistáló haematuria (vékony-basalis-membran-nephropathia) és könnyülánc-proteinuria (benignus monoclonalis gammopathia) együttes elöfordulása egy középkorú férfiban.

IgG lambda type of monoclonal gammopathy and thin basement membrane nephropathy were established in a middle-aged man examined because of persistent haematuria, lambda light-chain proteinuria and moderately diminished renal function. A 10% level of plasmocytosis was verified by bone-marrow aspiration. The more than 6-year follow-up showed the gammopathy to be benign. The thin basement membrane nephropathy was verified by electronmicroscopic analysis of renal tissue obtained by percutaneous renal biopsy: lamina densa of the glomerular capillaries thinned to 30-100 nm. In spite of the usually good outcome of thin basement membrane nephropathy, in this case it was accompanied by glomerular sclerosis, subsequent destruction of nephrons, hypertensive vascular alterations and a clinical deterioration of the renal function after 4 years. A rebiopsy excluded the possible complications (amyloidosis, non-amyloid immunoglobulin nephropathy, cylinder nephropathy, etc) of light-chain proteinuria.

[The effect of chronic alcohol consumption on blood pressure]. / A tartós alkoholfogyasztás hatása a vérnyomásra.

In 1984, a hypertension screening programme was carried out on 13,772 adult subjects in conjunction with a radiological tuberculosis project in the Hungarian town of Csongrád. Among other factors, the effects of a long-lasting and heavy alcohol intake on blood pressure levels were investigated. 21.4% of the men and 2.3% of women admitted to being regular alcohol consumers. Direct and significant relationships were found between the quantity of alcohol consumed and both the systolic (p less than 0.001) and diastolic (p less than 0.05) blood pressures. The prevalence of hypertension (WHO criteria) was higher in heavy drinkers (29.9%) than in abstinent subjects (20.5%, p less than 0.001). When participants were subgrouped according to age groups only the men provided sufficient data. The systolic blood pressure of heavy drinkers was elevated as compared with that of non-drinkers.

[Secondary membranous glomerulonephritis]. / Secunder membranosus glomerulonephritis.

Following 689 percutaneous renal biopsies, membranous glomerulonephritis was proved in 68 patients. In 16 (23.5%) an underlying primary disease was verified, and thus the glomerulonephritis the secondary form. The primary disease was SLE in 5 cases, diabetes mellitus in 5 cases, rheumatoid arthritis in 3 cases, chronic active hepatitis in 2 cases, an ulcerative colitis and eosinophilic angiolymphoid hyperplasia in 1 patient. As initial sign, nephrotic syndrome emerged in 87.5% of the 16 cases. Microscopic haematuria was observed in half of the patients, as was hypertension, while acute renal failure presented in only 1 case. Histologically, in 13 cases the predominance of early glomerular alterations was characteristic, while in 9 cases the picture proved to be equivocal and accompanied by some degree of interstitial alterations. During combined treatment, remission was achieved in 75%. Two patients with SLE died, but not as a consequence of renal failure. Transient side-effects of the treatment were registered in 5 cases. The principal pathogenetic and clinical differences between the individual secondary nephritis forms, and the difficulty of their differentiation from the idiopathic cases, even on repeated examination, are emphasized. In 3 patients the possibility of secondary renal processes was suggested by the histological picture, and this was proved by the detailed clinical findings.

Effects of nephrectomy on hypertension, renin activity and total renal function in patients with chronic renal artery occlusion.

Eight hypertensive patients (5 men and 3 women, aged between 31 and 64 years) with chronic total occlusion of one renal artery were observed for the past ten years. The peripheral plasma renin activity (PRA) and the renal vein PRA ratio (mean 3.18) were abnormally high in all cases. Because of the small size of the affected kidney (less than 9 cm in length), nephrectomy was the chosen treatment. Postoperative investigations revealed decreases in blood pressure (from 202/118 to 147/93 mmHg), peripheral PRA (from 6.05 to 1.05 ng/ml/h; P less than 0.001), serum creatinine (from 188.8 to 145.1 mumol/100 ml) urine volume (from 1937.5 to 1214.3 ml) and increases in endogenous creatinine clearance (from 36.57 to 53.0 ml/min). The results suggest that, apart from the decrease in blood pressure, the nephrectomy led to the disappearance of a factor which depresses the renal function in cases of chronic renal artery occlusion and which may be related to the renin-angiotensin system.

Primary Sjögren's syndrome with secondary hyperparathyroidism.

The case history of a 43-year-old woman with primary Sjögren's syndrome is presented: in 1970, xerostomia and keratoconjunctivitis sicca; in 1980, arthritis; in 1982, chronic tubulointerstitial nephritis with renal tubular acidosis and vasopressin-resistant hyposthenuria. The renal function gradually deteriorated. Chronic atrophic gastritis with vitamin B12 deficiency and chronic duodenitis with diminished disaccharidase activity in the mucosa were also diagnosed. From 1985, repeated multiple fractures of the ribs occurred, with secondary hyperparathyroidism in the background. The renal and intestinal involvement suggests that, besides the elevated parathyroid hormone level, an acquired vitamin D deficiency plays a pathogenetic role in severe osteopenia. The patient is being treated at present by haemodialysis, and subtotal parathyroidectomy and renal transplantation are planned.

[Pheochromocytoma in Recklinghausen neurofibromatosis]. / Pheochromocytoma Recklinghausen neurofibromatosisban.

The authors describe the case of a 38-year-old hypertensive woman who suffered from neurofibromatosis, pheochromocytoma, scoliosis and diabetes mellitus. Because of the residual pheochromocytoma surgical intervention was repeated. According to the available literature this is the first case in Hungary where pheochromocytoma was associated with neurofibromatosis.

Intersalt in Newfoundland and Labrador.

In Intersalt, positive relations between 24-hour urinary sodium and potassium excretion and blood pressure were observed in over 10,000 men and women in 52 centers around the world. Body mass index (BMI), alcohol intake and smoking showed different associations with blood pressure in various population groups. We investigated these variables in the 2 Canadian centers and could not confirm the sodium-potassium relationship. In a multiple stepwise regression analysis, BMI and alcohol had the strongest relation with blood pressure in men. Among the female participants, BMI and sodium were the most influential factors on systolic blood pressure. For diastolic blood pressure, BMI and smoking showed the strongest significance. Neither in men nor in women could the influence of high sodium and low potassium excretion on blood pressure be discerned.

[Glomerulonephritis in diabetics]. / Glomerulonephritis diabeteses betegekben.

Diagnosis of glomerulonephritis (GN) is rare among diabetics and few data relevant to this issue can be found in literature. In Institute of Pathology of "Szent-Györgyi Albert" University of Medicine the presence of GN was found in cases during the examination of renal biopsy material of 36 diabetics. All patients have suffered from diabetes mellitus of 2nd type and of less than 10 year existence, requiring no insulin treatment. In 2 cases diffuse diabetic glomerulosclerosis associated with GN. It is emphasized that kidney biopsy and its complex--light and electronmicroscopic and immunhistological--examination are essential to the diagnosis of GN of diabetics.

Hypertension screening in a Hungarian town.

In conjunction with a radiological tuberculosis project, a hypertension screening programme was carried out in 1984 on 13,772 people (74% of the eligible adult population) in the Hungarian town of Csongrád. In the younger age groups the blood pressure was found to be higher amongst men, whilst in older groups the women had higher blood pressures. By the WHO criteria, systolic hypertension was detected in one-third of the population and diastolic hypertension in one-sixth. Of the hypertensive patients detected, 34% were previously unaware of their diagnosis. The prevalence of hypertension was elevated particularly amongst obese persons and in the sub-group of physical (blue collar) workers aged over 60 years. There was a significant correlation between alcohol consumption and both systolic and diastolic blood pressures. Hypertension was found in 29.9% of heavy drinkers but in only 20.5% of moderate drinkers or total abstainers.

[Three cases of mycobacteriosis with gastrointestinal localization]. / Gastrointestinalis lokalizációjú mycobakteriosis három esete.

The authors present three patients having primary microbacterial infections which involved the gastrointestinal tract. A short survey of the clinical features and the difficulties arriving at definitive diagnosis is given. They discuss the differential diagnostic problems in each case--without an unequivocal bacterial findings--on the basis of histologyc data and of therapeutic response which ultimately proved the mycobacterial nature of the infection.

Bilateral renal malacoplakia in systemic lupus erythematosus and adrenogenital syndrome.

We report a case of an 8-year-old girl with adrenogenital syndrome secondary to adrenocortical hyperplasia. Thirteen years later systemic lupus erythematosus developed with lupus nephritis. In spite of complex continuous immunosuppressive therapy, she died from terminal renal failure. At autopsy, extensive bilateral renal malacoplakia was discovered. The role of recurrent urinary tract infections and of immunological disturbances in the pathogenesis of malacoplakia is discussed.

Comparison of BAY e 5009 (nitrendipine) with dihydralazine in Wistar rats with experimentally induced nephritis.

Chronic administration of nitrendipine (N) prevented the development of serious renal damage in Wistar rats with experimental glomerulonephritis. This effect is in sharp contrast with the action of dihydralazine (D). In the two treated groups, the blood pressure levels were in the same range and had returned to values of about 140 mm Hg. The heart rate and the increase in body weight were identical. Daily urinary protein excretion was significantly lower in the N-treated rats (p less than 0.001). During the experiment, 4 of the 12 D-treated and 6 of the 12 untreated animals died. In contrast, all of the N-treated rats survived. Their blood urea nitrogen and serum creatinine levels were significantly lower (p less than 0.01). Histologically, all untreated nephritic animals and three of eight D-treated rats revealed severe arteriopathy in the large vessels of the kidney and focal calcification of the glomerular and tubular basement membranes. Neither vascular changes nor basement membrane calcification were found in the kidneys of the N-treated group. These results suggest the direct renal prophylactic effect of N by prevention of the cellular calcium overload and the extracellular deposition of calcium.