Influence of sex and experimental protocol on the effect of maternal deprivation on rectal sensitivity to distension in the adult rat.

Neonatal maternal separation induces visceral hyperalgesia before and after stress in male rats. This study compares the effects on sensitivity to rectal distension in adult male and female rats, using two protocols of deprivation. Between postnatal days 1 and 14, maternal deprivation was performed for 2 h per day according to a protocol of type M (removal of all pups from home cage) or type P (separation of half of littermates). Visceral sensitivity was assessed at 12 weeks of age by the number of abdominal contractions induced by rectal distension before and after restraint stress. Calcitonin gene-related peptide (CGRP) was identified in the rectal wall by immunohistochemistry. In basal conditions, both separation protocols induced hyperalgesia, that was greater after type M than type P, and in females than in males for type P separation. Acute restraint stress induced hyperalgesia in control females only, and this effect was similarly enhanced by both type P and M separation. No difference was found between controls and deprived rats in rectal CGRP immunoreactivity which was greater in females and increased after rectal distension. These results indicate that long-term visceral hyperalgesia depends upon the type of maternal deprivation and that females are more sensitive than males.

Cholecystokinin fails to promote pancreatic regeneration in diabetic rats following the induction of experimental pancreatitis.

The aim of the present study was to investigate the spontaneous and cholecystokinin-octapeptide (CCK-8)-promoted laboratory changes and morphological alterations in rats with arginine (Arg)-induced pancreatitis in which diabetes had been induced with streptozotocin (STZ). Male Wistar rats were used in our experiments. Pancreatitis was induced by arginine, diabetes by STZ and regeneration was promoted by CCK-8. The serum amylase, glucose and insulin levels, the pancreatic contents of protein, DNA, amylase, trypsinogen and lipase, the pancreatic weight/body- weight ratio (pw/bw) and the plasma glucagon level were examined 1, 3, 7, 14 and 28 days after pancreatitis induction. Pancreatic tissue samples were examined by light microscopy and immunostaining on paraffin-embedded sections. The insulin and glucagon-containing cells were visualized by using monoclonal antibodies. The administration of low doses of CCK-8 accelerated the processes of regeneration following Arg-induced pancreatitis, but in rats that were also diabetic, pancreatic regeneration was not observed. The administration of low doses of CCK-8 seems to reduce the pancreatic beta -cell number and function in diabetic rats. The pancreatic endocrine function was further deteriorated by simultaneous Arg-induced pancreatitis. The diabetic state appeared to shift the normal pancreatic enzyme content (decreased amylase and increased trypsinogen) in this study.

Continuous enteral feeding has an attenuating effect on the exocrine pancreas in rats.

INTRODUCTION: Recent clinical observations suggest that continuous enteral feeding (CEF) may exert a beneficial effect in the management of inflammatory pancreatic diseases. Its effects on the exocrine pancreas, however, remain only partially investigated. AIM: To examine the effects of CEF on the exocrine pancreas in rats. METHODOLOGY: Eight male Wistar rats were intrajejunally cannulated, and CEF was started on postoperative day 6. In 10 control animals, laparotomy was followed by intragastric feeding (GF) with the same nutriment (Osmolite, Abbott) from postoperative day 6. The daily discharge was 24 kcal in both groups. After 5 days of feeding, the pancreas was removed; its weight and its protein, DNA, trypsin, and lipase contents were determined; and the exocrine pancreas was also examined for structural changes. RESULTS: The results revealed no significant difference in body weight loss between the two groups of animals, whereas the pancreas weight/body weight ratio was lower (p < 0.01) in the CEF group. The pancreatic protein, DNA, and enzyme contents were decreased (p < 0.01) after CEF as compared with the values for the GF group. Histologic examinations demonstrated clear decreases in acinar size and in the zymogen content of the pancreas in the CEF animals. CONCLUSION: This study clearly indicates that CEF reduces the enzyme production of the pancreas.

[Effect of continuous enteral feeding on pancreas exocrin function in rats]. / Folyamatos enteralis táplálás hatása a hasnyálmirigy exocrin múködésére patkányban.

The aim of this study was to examine the effects of continuous enteral feeding (CEF) on the exocrine pancreas in rats. Eight male Wistar rats were intrajejunally cannulated and CEF was started on postoperative day 6. In 10 control animals, laparotomy was followed by intragastric feeding (GF) with the same nutriment (Osmolite, Abbott, 254 mosm/l) from postoperative day 6. The daily discharge was 24 kcal in both groups. After five days of feeding, the pancreas was removed, its weight and its protein, DNA, trypsin and lipase contents were determined. The results revealed no significant difference in body weight loss between the two groups of animals, whereas the pancreas weight/body weight ratio was lower (p < 0.01) in the CEF group. The pancreatic protein, DNA, trypsin and lipase contents were decreased (p < 0.01) after CEF as compared with the values for the GF group.

Decorin and actin expression and distribution in patients with chronic hepatitis C following interferon-alfa-2b treatment.

BACKGROUND/AIMS: Chronic hepatitis C can lead to cirrhosis and hepatocellular carcinoma. Interferon-alfa therapy may prevent the progression of the disease. The expressions of decorin and alfa-smooth muscle cell actin of the extracellular matrix play a central role in liver fibrosis. We set out to assess the expressions of these proteins in chronic hepatitis C patients, and to evaluate how they can be modified by interferon-alfa therapy. METHODS: Twenty chronic hepatitis C patients received interferon-alfa-2b therapy for 6 months (group I) or 12 months (group II). Liver biopsy samples were taken before and after the therapy. The alfa-smooth muscle actin-positive cells were determined with a monoclonal antibody, and decorin expression was detected with a polyclonal antibody. The cells were evaluated with a semiquantitative scoring method. For statistical analysis, non-parametric methods were used. RESULTS: Before the therapy, alfa-smooth muscle actin-labeled cells and marked decorin expression were present throughout all the acinar zones. Interferon-alfa-2b therapy resulted in significant decreases in both the number of alfa-smooth muscle actin-positive cells and the decorin expression. The alfa-smooth muscle actin-positive cells and decorin expression correlated with the histological activity index (R=0.72, p<0.03, R=0.68, p<0.05). CONCLUSIONS: This study demonstrates that a large number of alfa-smooth muscle actin-positive cells and a marked decorin expression are frequent findings in chronic hepatitis C. Treatment with interferon-alfa-2b for 12 months reduced the number of labeled cells and the decorin expression. The results suggest that interferon-alfa-2b is capable of interfering with fibrogenesis in an early and presumably still reversible phase of chronic hepatitis C.

Histological evaluation of the response to interferon-alpha therapy in chronic hepatitis C.

BACKGROUND AND AIMS: The response rate of interferon-alpha (IFN-alpha), recently introduced in the treatment of chronic hepatitis C, is merely 25-50%. The aims of this follow-up study were to compare the efficacy of 6 and 12-month IFN-alpha treatment via liver biopsy scores and to evaluate the correlation with the biochemical response. PATIENTS AND METHODS: Twenty chronic hepatitis C patients were studied; 10 received IFN-alpha therapy for 6 months and 10 for 12 months. Liver biopsy material was taken before and after therapy. RESULTS: There was a significant serum alanine aminotransferase (ALT) level improvement in both groups, but a significant histological improvement in necroinflammatory activity (grade) only in the 12-month group. The Chevallier stage scores demonstrated a significant progression in both groups. CONCLUSIONS: Twelve-month IFN-alpha treatment affords a better response in the liver histology grade and serum ALT level, but does not influence the staging; a normal ALT does not guarantee hepatitis inactivity. Liver biopsies appear indispensable for monitoring.

[Food allergy in patients with respiratory allergy. Diagnostic possibilities and problems]. / Légúti allergiás betegek étalallergiája. Diagnosztikai lehetöségek és problémák.

UNLABELLED: In the past two years the authors examined 28 patients with abdominal complaints and allergic respiratory symptoms. Detailed internal, gastroenterological, allergological examinations were made. METHODS: 1 skin Prick-test (SPT) with inhalative and nutritive panel 2. measuring of food-specific (gliadin, alpha-lactalbumin beta-lactoglobulin, ovalbumin) IgG-antibody level detecting with ELISA method, 3. leukocyte migration inhibition (LMI) test against the same foodstuffs, 4. histological examination of the stomach and the duodenum especially for mucosal mastocytes (MMCs). RESULTS: 1. SPT was positive in 23/28 patients for inhalative, but in the 5 cases we did not identify any inhalative allergen. The SPT for the main foodstuffs were positive in 18 patients while in 3 other patients there was urtica only for the other antigens. 2. The food-specific IgG-antibody level was increased in 18/27 patients against one or more antigens. The SPTs and the antibody determination showed identity in 8/18 cases. 3. The LMI tests were positive against one or more main food-products in 23/27 cases. There was common positivity in respect of antigens (between LMI test and antibody identification) in 17 cases. Pathological immunological reactions were presented against the same main foodstuffs with at least two methods for flour in 11, for egg in 10 and for milk in 12 patients. Endoscopic examinations were performed in 27 cases. The number of the MMCs were increased in 22/27 patients. After a specific elimination diet open-food challenges were performed and they confirmed the results of the in vitro and in vivo examinations. CONCLUSION: It is common that the respiratory allergic symptoms in atopic patients accompanied with food allergy for the main foodstuffs caused not only more severe respiratory symptoms, but abdominal complaints too. In respect to the many positive LMI tests the late-type hypersensitivity have important pathogenetical role in it. This three methods together define well the main food-products, which can be antigens as well. The examination of the MMCs supports the local disturbance in the immunoregulatory system.

[Histological characteristics of chronic hepatitis C in biopsy material]. / Krónikus C vírus hepatitis szövettani jellemzöi biopsziás anyagunkban.

BACKGROUND/AIMS: Hepatitis C virus (HCV) infection is one of the most important diseases with high chronicity rate (50-80%) leading to end-stag cirrhosis and hepatocellular carcinoma. Hepatic histology shows a characteristic but not diagnostic picture. The aim of this study was to evaluate the characteristic histological findings in correlation with epidemiological features in our liver biopsy material. PATIENTS/METHODS: 106 liver biopsies were studid between 1993-1996. All patients (60 males, 46 females, age between 11-81 years, mean age: 43 years) were found to be positive for HCV antibody by a second-generation ELISA method. The biopsy materials were fixed in buffered formalin and having embedded in paraffin, stained with hematoxylin and eosin, periodic acid-Schiff after diastase digestion, Gömöri's reticulin stain and picrosirius red for collagen. The histological evaluation was based upon the new classification of chronic hepatitis proposed by Desmet et al. The statistical analysis was performed by the Chi square test. RESULTS: Minimal chronic hepatitis (HAI: 1-3) was found in 14 (13.2%), mild chronic hepatitis (HAI: 4-8) in 69 (65.09%) and moderate chronic hepatitis (HAI: 9-12) in 23 (21.69%) cases, while assessment of fibrosis (staging) resulted fibrosis 0/1 in 44 (41.5%), fibrosis 2 in 14 (13.2%), fibrosis 3 in 37 (34.9%) and cirrhosis (fibrosis 4) in 11 (10.37%) cases. Among histological features of chronic hepatitis C, the frequency of steatosis (70.75%), lymphoid F/A (63.2%), and bile duct lesions (12.26%) have paralelly increased with activity (grade) of hepatitis and these changes were more pronounced in moderate chronic hepatitis (p < 0.001). CONCLUSIONS: More than half of chronic hepatitis C patients presented mild histological lesions with stage 1 fibrosis. Lymphoid F/A, bile duct damage and steatosis are important diagnostic features that show a strong correlation with the activity of chronic hepatitis. The assessment of fibrosis (stage: 3 and stage: 4) in mild chronic hepatitis cases does alert the hepatologist to perform the liver biopsy to detect the fibrotic changes in chronic hepatitis C.

[Drug therapy of gastroesophageal reflux (a prospective controlled clinical trial)]. / A gastrooesophagealis reflux betegség gyógyszeres kezeléséröl (prospektív kontrollált klinikai vizsgálat).

One year follow up(1.5, 3, 6, 12 months) study was established to examine the role of several classes of drugs in the treatment of reflux disease in 40 patients on the basis of objective control parameters (pH-metry, endoscopy, histology). The therapy was initiated, respectively, the different stage of severity (Savary-Miller): in stage 0 sucralfate + domperidone, in stage I and II: ranitidine + domperidone and in stage III-IV omeprazole was introduced. Our results proved that sucralfate + domperidone is curative on reflux oesophagitis in stage 0 cases. In stage I sucralfate and domperidone were effective in 3 of 9 cases, ranitidine + domperidone was optimal in 5 of 9, and omeprazole was required in 1 of 9 patients. In stage II, ranitidine + domperidone was effective only in 4 of 11 patients, and the initial therapy was modified to omeprazole in 7 of 11 patients to find the optimal drug in this stage. In stage III and IV only omeprazole showed curative effect and the doses required were 20 mg in 8 of 13 and 40 mg in 5 of 13 patients. The complaints improved in 34 of 40 patients after 6 weeks treatment, while histological healing of reflux oesophagitis was observed in 12 of 40 cases. After 3 months the endoscopic healing rate was 28/40, but histological healing could be reached after 6 months of optimal treatment in 30 of 40 cases. We can conclude, that the optimal drug selection may result a rapid improvement of complaints, but endoscopic and histological regeneration of the oesophageal mucosa is more graduated with time. The healing process of the reflux oesophagitis requires 3 months. Proton pump inhibitor drugs have an enhanced role in the treatment of gastrooesophageal reflux disease, and our results proved that the efficient and safety treatment of mild form (stage II) of disease requires the administration of proton pump inhibitors.

[Histo-pathological evaluation of response to 6 and 12 months of interferon alpha therapy]. / Krónikus C hepatitis klinikopatológiai képének alakulása 6 és 12 hónapos interferon-alfa kezelést követóen.

BACKGROUND AND AIMS: Interferon-alfa (IFN-alfa) has recently been introduced for chronic C hepatitis treatment; however, the response rate is merely 25-50%. The aims of this follow-up study were to compare the efficacy of 6 and 12-month IFN-alfa treatment via liver biopsy scores and to evaluate the correlation with the biochemical response. PATIENTS AND METHODS: 20 chronic C hepatitis patients were studied. 10 patients received IFN-alfa therapy for 6 months, and 10 for 12 months (3 million units three times a week). Liver biopsy material was taken before and after therapy. RESULTS: There was a significant serum alanine aminotransferase (ALT) level improvement in both groups, but a significant histological improvement in necroinflammatory activity (grade) occurred only in the 12-month group. The Chevallier stage scores demonstrated a significant progression in both groups. CONCLUSIONS: 12-month IFN-alfa treatment affords a better response in the liver histology grade and serum ALT level, but not the stage; a normal ALT does not guarantee hepatitis inactivity. Liver biopsies appear indispensable for monitoring the fibrotic changes in chronic C hepatitis.

Beneficial effects of pentoxifylline treatment of experimental acute pancreatitis in rats.

UNLABELLED: The purposes of this study were to determine the tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels after the induction of acute necrotizing pancreatitis, and to establish the effects of pentoxifylline on cytokine production. METHODS: acute pancreatitis was induced by the retrograde injection of 200 microliters taurocholic acid into the pancreatic duct in male Wistar rats. The serum amylase activity, the wet pancreatic weight/body weight ratio, and the TNF and IL-6 levels were measured. Seven mg/kg pentoxifylline were administered intraperitoneally at the time of operation 6, 12 or 24 h later. Rats were killed 6, 24, 48 or 72 h after the operation. RESULTS: the TNF bioassay revealed high levels of TNF (30.2 +/- 5.4 U/ml, 35.0 +/- 5.0 U/ml and 36.6 +/- 6.0 U/ml) in the control group at 6, 24 and 48 h and (54.1 +/- 20 U/ml and 10.9 +/- 4.2 U/ml) in the pentoxifylline-treated group at 6 and 24 h, respectively, whereas the level had decreased to zero in the pentoxifylline-treated group at 48 h. The IL-6 bioassay likewise demonstrated high levels of IL-6 in the control group at 48 h and in the pentoxifylline-treated group at 6 and 24 h, and markedly decreased levels in the pentoxifylline-treated group at 48 h (7083 +/- 2844 pg/ml, 6463 +/- 1307 pg/ml, 10,329 +/- 5571 pg/ml vs 137.5 +/- 85.5 pg/ml, respectively, P < 0.05). The high mortality observed in the pancreatitis group (43%) was decreased by pentoxifylline administration to 11%. CONCLUSION: these results demonstrate that pentoxifylline very effectively inhibits cytokine production in acute pancreatitis.

Beneficial effect of octreotide treatment in acute pancreatitis in rats.

CONCLUSIONS: Octreotide treatment contributes to the regulation of tumor necrosis factor (TNF) production in sodium taurocholate-induced acute necrotizing pancreatitis in rats. Owing to its complex effect, octreotide can partially ameliorate the deleterious consequences of acute necrotizing pancreatitis. Elevated TNF and interleukin-6 (IL-6) levels in the peritoneal fluid may be considered a consequence of the activation of peritoneal macrophages. BACKGROUND: The effects of octreotide on exocrine pancreatic function have been investigated in numerous studies, but little attention has been paid to its influence on cytokine production in acute pancreatitis. METHODS: Acute pancreatitis was induced by the retrograde injection of taurocholic acid into the pancreatic duct in male Wistar rats. Serum amylase activity, wet pancreatic weight/body weight (pw/bw) ratio, and TNF and IL-6 levels were measured. Four micrograms/kg of octreotide was administered subcutaneously at the time of induction of pancreatitis and 24 or 48 h later. Rats were sacrificed 6, 24, 48, or 72 h after the operation. RESULTS: The serum amylase level and pancreatic weight to body weight ratio were decreased significantly in the octreotide-treated group. The serum TNF level was decreased significantly in the octreotide-treated group as compared with the control group at 6, 24, and 48 h (0.6 +/- 1.5, 2.0 +/- 3.3, and 0 vs 50 +/- 15.5, 37.5 +/- 18.4, and 13.1 +/- 12.5 U/mL, respectively). The ascites TNF level was decreased to 0 in the octreotide-treated group and was elevated in the control group at 72 h (28.0 +/- 49.0 U/mL). IL-6 production in ascites was extremely high in both groups at 6 h (80,000 +/- 43,817 pg/mL and 58,500 +/- 33,335 pg/mL), but the difference was not significant.

[Pathology and pathogenesis of viral hepatitis]. / A vírushepatitisek patológiája és patogenezise.

Several factors viral genotype, mutations, vírus-host interaction, expression of viral proteins and host immune-reaction are very important in the pathogenesis of hepatotrop viral infections. Activation of Fas/Fas ligand system occurs during hepatitis which is responsible for the apoptosis of vírus infected hepatocytes. The histological features in chronic hepatitis can be classified based on the activity of near inflammatory alterations ("grade"). Stage of chronic hepatitis describes the degree of fibrosis and architectural alterations.

[Cytokines in experimental acute pancreatitis]. / Citokinek kísérletes akut pancreatitisben.

The authors induced acute necrotizing pancreatitis in Wistar rat by intraductal injection of taurocholic acid (150 microliters or 200 microliters 6%). Plasma values of amylase, TNF, IL-6 levels and wet pancreas weight/body weight ratio have been determined. Histologic analysis of pancreas proved severe acute necrotizing pancreatitis with microabscess formation and beginning respiratory distress syndrome was observed in the lungs, TNF and IL-6 levels increased significantly after administration of 200 microliters 6% taurocholic acid. The authors emphasise the importance of cytokines in the development of acute necrotizing pancreatitis.

Spontaneous and cholecystokinin-octapeptide-promoted regeneration of the pancreas following L-arginine-induced pancreatitis in rat.

CONCLUSION: In L-arginine (Arg)-induced pancreatitis, evidence of acute inflammation was observed on d 1-3. Continuous tissue atrophy became visible at the sites of previous pancreatic necrosis, with simultaneous regeneration of the pancreas, mainly around the Langerhans islets. Administration of low doses of cholecystokinin-octapeptide (CCK-8) increased the inflammatory signs of pancreatitis in the early phase, but subsequently diminished the level of atrophy and accelerated the processes of regeneration in this model of pancreatitis. BACKGROUND: The aim of this work was to study the regenerative processes following Arg-induced pancreatitis in rats. Besides the spontaneous regeneration, the effects of low doses of CCK-8 on the laboratory and morphologic parameters in this type of experimental pancreatitis were investigated. METHODS: Male Wistar rats were divided into three groups. In group I, the rats received 200 mg/100 g body weight of Arg i.p. twice, at an interval of 1 h, and 0.5 mL saline was administered s.c. twice daily. In group II, besides the same amount of Arg, the rats received 1 microgram/kg of CCK-8 s.c. in 0.5-mL saline twice daily (7 AM and 7 PM). In the control animals (group III), an identical amount of glycine was administered i.p. instead of Arg at the same times. The rats were examined on d 1, 3, 7, 14, and 28 after pancreatitis induction. The pancreatic weight/body weight ratio (pw/bw) was calculated in each case. The serum levels of amylase, and glucose and the pancreatic contents of soluble protein, trypsin, amylase and DNA were determined, and histologic examinations were performed. RESULTS: In groups I and II, both pw/bw (3.5 +/- 0.2 mg/g and 4.1 +/- 0.28 mg/g, respectively) and the serum amylase level (8900 +/- 560 IU/L and 11100 +/- 1390 IU/L, respectively) were significantly elevated on d 1 vs group III (2.1 +/- 0.06 mg/g and 5562 +/- 373 IU/L, respectively). Pw/bw was significantly decreased in groups I (0.96 +/- 0.12 mg/g, 0.8 +/- 0.1 mg/g, and 1.8 +/- 0.1 mg/g, respectively) and II (1.4 +/- 0.15 mg/g, 1.7 +/- 0.2 mg/g, and 1.95 +/- 0.1 mg/g, respectively) on d 7, 14, and 28 vs group III (2.6 +/- 0.3 mg/g, 3.1 +/- 0.15 mg/g, and 2.7 +/- 0.1 mg/g, respectively), whereas in group II it was significantly elevated vs. group I on d 7 and 14. The pancreatic contents of soluble protein, DNA, trypsin and amylase were significantly decreased on d 3-14 in groups I and II vs group III. The pancreatic DNA level was significantly elevated in group II (1.23 +/- 0.2 mg/pancreas) vs group I (0.7 +/- 0.1 mg/pancreas) on d 7. In group II, the soluble protein (73.1 +/- 15.5 mg/pancreas) and amylase (1104 +/- 160 IU/pancreas) levels were significantly elevated on d 14 as was that of trypsin (27.2 +/- 3.1 IU/pancreas) on d 28, vs group I (26.4 +/- 5.3 mg/p, 525 +/- 111 IU/pancreas, and 16.3 +/- 1.1 IU/pancreas, respectively). On histologic sections, the signs of acute inflammation of the pancreas were more pronounced in group II than in group I on d 1-3. After that time, in spite of the progressive atrophy of the pancreas, the signs of tissue repair were more expressed in group II.

Time-course changes in serum cytokine levels in two experimental acute pancreatitis models in rats.

Activated leukocytes and cytokines have important roles in the multi-system involvement during acute pancreatitis. The changes in the serum level of tumor necrosis factor-a (TNF-alpha) and interleukin-6 (IL-6) over time were investigated in two experimental acute pancreatitis models in rats. Mild edematous pancreatitis was induced with an overdose of cholecystokinin octapeptide (CCK-8), while a severe hemorrhagic form of pancreatitis was induced by ligation of the common bilio-pancreatic duct. The rats were examined 2, 4, 8, 16, 24 and 48 h after pancreatitis induction. The severity of the inflammation was assessed by measurement of the serum amylase activity, quantification of the edema, and histological examination. Serum TNF-alpha and IL-6 were determined by bioassay, using the TNF-sensitive WEHI 164 and the IL-6-dependent B9 cell lines, respectively. In CCK-8-induced acute pancreatitis, the pancreatic weight/body weight ratio (pw/bw) and amylase level were significantly elevated at 2 h, and the maximum levels were observed at 4 h (8.19 +/- 1.13 mg/g and 69.4 +/- 12.8 x 10(3) U/ml, respectively). Both parameters subsequently decreased continuously during the observation period. The serum IL-6 level was significantly increased at 4 h relative to the controls (123.3 +/- 5.8 vs 37.5 +/- 15 pg/ml), and then decreased continuously. In this model, only a moderate level of serum TNF-alpha was observed at 2 h. In the biliary type of acute pancreatitis, the ratio pw/bw increased continuously during the study and reached the maximum level at 48 h relative to the sham-operated control (8.8 +/- 1.4 vs 5.3 +/- 0.8 mg/g). The serum amylase level was significantly elevated at 2 h (43.2 +/- 13 x 10(3) U/ml), but then decreased continuously. The serum IL-6 reached its maximum level at 16 h (3800 +/- 447 pg/ml). In this model, increased TNF-alpha levels (75-300 U/ml) were measured 8, 16 and 24 h after pancreatitis induction. The results led to correlations between the serum IL-6 levels and the biochemical and morphological severity of acute pancreatitis in both experimental models. The data suggest that IL-6 and TNF-alpha may participate in the pathogenesis of these types of acute pancreatitis.

Cytokine level changes in L-arginine-induced acute pancreatitis in rat.

The role of different cytokines in the pathogenesis of L-arginine (Arg)-induced acute pancreatitis in rat, and the ability of KSG-504, a novel cholecystokinin receptor antagonist, to exert protection in this type of acute pancreatitis was evaluated. Male Wistar rats received 250 mg/100 g body weight of Arg intraperitoneally twice, at an interval of 1 h. Control rats received instead the same amount of glycine at the same times. Fifty mg/kg KSG-504 was injected subcutaneously 0.5 h before and 6, 18 and 36 h after the first Arg administration. Rats were examined 12, 24 and 48 h after pancreatitis induction. To assess the severity of inflammation, the edema was quantified, the serum amylase level was measured, and histologic examinations were performed. Serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels were determined by bioassay, using the TNF-sensitive WEHI 164 and the IL-6-dependent B9 cell lines, respectively. In Arg-induced acute pancreatitis, the amylase level was increased significantly at 12 h (48.600 +/- 3.980 U/l) and 24 h (30.800 +/- 3.813 U/l) vs. the control group (6.382 +/- 184 U/l). No significant alteration in the ratio pancreatic weight/body weight was found in the different groups. However, in Arg-induced acute pancreatitis, both the TNF-alpha (15.1 +/- 6.9 U/ml) and the IL-6 (39.6 +/- 19.2 pg/ml) levels were already elevated significantly at 12 h vs. the controls (3.1 +/- 0.8 U/ml and 15.2 +/- 3.1 pg/ml, respectively) and remained elevated at 24 and 48 h. Simultaneous KSG-504 administration did not modify the measured cytokine levels. No significant changes in plasma CCK levels were observed. In Arg-induced acute pancreatitis, histological evaluation revealed diffuse but microfocal necrobiotic alterations. No marked protective effects of KSG-504 were observed on histological sections. These results suggest that excessive doses of Arg induce severe acute pancreatitis in rat, with a simultaneous cytokine level elevation. Endogenous CCK does not seem to play an essential role in the pathogenesis of Arg-induced acute pancreatitis.

Time-course changes in pancreatic laboratory and morphologic parameters in two different acute pancreatitis models in rats.

The aim of this work was to study in rats the temporal course of laboratory parameters and morphologic features in acute pancreatitis induced by cholecystokinin octapeptide (CCK-8) or by a closed duodenal loop. Pancreatitis was induced either with an overdose of CCK-8 (3 x 75 micrograms/kg at 1 h intervals) or by ligation of the duodenum on both sides of the bilio-pancreatic duct. The animals were examined at 0, 2, 4, 8, 16 and 24 h after AP induction. In CCK-8-induced acute pancreatitis, the pancreatic weight/body weight ratio (8.2 +/- 1.1 mg/g) and the amylase level (44.8 +/- 7.5 x 10(3) U/ml) were significantly increased vs. the controls (4.5 +/- 0.8 mg/g and 3.3 +/- 0.2 x 10(3) U/ml, respectively) 2 h after the intervention. The plasma CCK was significantly increased at 4 h (4.55 +/- 1.7 pM) and remained elevated thereafter. The tissue malonyldialdehyde concentration was significantly elevated at 8 h (0.28 +/- 0.07 mumol/mg pancreas) vs. the controls (0.20 +/- 0.02 mumol/mg pancreas). In closed duodenal loop-induced acute pancreatitis, the ratio pancreatic weight/body weight steadily increased during the study; it reached its maximum level at 24 h (7.1 +/- 0.5 mg/g) vs. the sham-operated control (4.8 +/- 0.9 mg/g). The serum amylase level was significantly elevated at 2 h (47.1 +/- 9.3 x 10(3) U/ml), and then decreased steadily. Plasma CCK values were significantly higher than the controls throughout the study. A significant increase in the tissue malonyldialdehyde concentration (0.94 +/- 0.15 mumol/mg vs. 0.20 +/- 0.01 mumol/mg pancreas) appeared at 4 h. Our data indicate that in CCK-8-induced acute pancreatitis the laboratory signs of pancreatitis are most expressed at 4 h, whereas the morphologic changes culminate 8 h, following the last CCK injection. In closed duodenal loop-induced acute pancreatitis, the histologic findings showed a progressive deterioration. Endogenous CCK and oxygen-derived free radicals seem to play a role in the pathogenesis of both types of acute pancreatitis.

[Collagenous sprue--a rare form of celiac disease in adulthood]. / Die kollagene Sprue--eine seltene Form der Zöliakie im Erwachsenenalter.

The authors report a case of collagenous sprue. This condition is characterized by coeliac type small bowel malabsorption, resistant to gluten free diet and other therapeutic efforts, associated with poor prognosis. The diagnosis depends on the histological demonstration of extensive collagenization of the lamina propria in the flat jejunal mucosa. This disease must be kept in mind at differential diagnosis of chronic diarrhea with progressive malabsorption, especially if it is resistant to gluten withdrawal in contrast to conventional coeliac disease.

[Collagen sprue--a rare form of adult celiac disease]. / Kollagén sprue--a felnöttkori coeliakia ritka formája.

The authors report the first case of collagenous sprue in Hungary. This condition is characterized by coeliac type small bowel malabsorption, resistant to gluten free diet and other therapeutic efforts, associated with poor prognosis. The diagnosis depends on the histological demonstration of extensive collagenization of the lamina propria in the flat jejunal mucosa. This disease must be kept in mind at differential diagnosis of chronic diarrhoea with progressive malabsorption, especially if it is resistant to gluten withdrawal than conventional coeliac disease.