Effects of treatment with melatonin and tryptophan on liver enzymes, parameters of fat metabolism and plasma levels of cytokines in patients with non-alcoholic fatty liver disease--14 months follow up.

Non-alcoholic fatty liver disease (NAFLD), most common chronic hepatic pathology, that occurs in the developed countries is estimated at 1/3 of the population. Amongst the numerous pathogenetic factors, oxidative stress and apoptosis of hepatocytes initiate many inflammatory processes and are involved in the progression of disease, particularly in transformation of non-alcoholic steatohepatitis (NASH) to cirrhosis. The aim of our study was to determine the effects of tryptophan and melatonin on the selected biochemical parameters in patients with NAFLD, and additionally, to evaluate the effects of tryptophan and melatonin in improvement of liver tissue in selected NAFLD patients. Seventy four patients with NAFLD confirmed by histopathological examination of liver biopsy samples, were admitted to the study. They were randomly assigned to three groups. Group I received the preparation Essentiale forte in the dose of 3 x 1 tablet per day and tryptophan 2 x 500 mg/day over the period of 14 months, group II received Essentiale forte and melatonin 2 x 5 mg/day over 14 months and group III received only Essentiale over the period of 14 months. In nine patients of groups I, II, and III, the liver biopsy was performed after 14-months of treatment period. Out of nine patients whom biopsy was performed, three of them were from group I, four from group II and two of them were from group III, respectively. After the 14-month treatment period, gamma-glutamyl transferase (GGPT) activity and levels of triglycerides and LDL-cholesterol were found to be significantly reduced in group I and II. The level of melatonin after the therapy was significantly elevated in group I and II and did not change in group III. Statistically significantly lower levels of IL-1, IL-6 and TNF-α were observed in patients receiving melatonin and tryptophan, comparing with group III treated with Essentiale forte only. These study findings demonstrate that melatonin and tryptophan substantially reduce the levels of pro-inflammatory cytokines and improve some parameters of fat metabolism in patients with NAFLD. In few patients with NASH melatonin and tryptophan reduced the inflammation in liver. We conclude that melatonin is worth considering for the therapy of NAFLD, particularly in patients with impaired fat metabolism accompanied by hypertriglyceridemia and hyper-LDL cholesterolemia.

Effects of melatonin and tryptophan on healing of gastric and duodenal ulcers with Helicobacter pylori infection in humans.

Melatonin (MT) and its precursor L-tryptophan (TRP) are implicated in the protection of gastric mucosa against aspirin-induced lesions and in the acceleration of healing of idiopathic gastro-duodenal ulcers, but no information is available whether these agents are also effective in healing of gastroduodenal ulcers accompanied by Helicobacter pylori (H. pylori) infection. In this study three groups A, B and C, each including 7 H. pylori-positive patients with gastric ulcers and 7 H. pylori-positive patients with duodenal ulcers, aging 28-50 years, were randomly assigned for the treatment with omeprazole 20 mg twice daily combined with placebo (group A), MT administered in a dose of 5 mg twice daily (group B) or TRP applied in a dose of 250 mg twice daily (group C). All patients underwent routine endoscopy at day 0 during which the gastric mucosa was evaluated and gastric biopsies were taken for the presence of H. pylori and histopathological evaluation. The rate of ulcer healing was determined by gastroduodenoscopy at day 0, 7, 14 and 21 after the initiation of the therapy. Plasma MT, gastrin, ghrelin and leptin were measured by specific RIA. At day 21, all ulcers were healed in patients of groups B and C but only 3 out of 7 in group A of gastric ulcers and 3 out of 7 in duodenal ulcers. Initial plasma MT showed similar low levels in all three groups but it increased several folds above initial values in ulcer patients at day 7, 14 and 21. Plasma gastrin and leptin levels showed a significant rise over initial values in patients treated with omeprazole and placebo, MT or TRP while plasma ghrelin levels were not significantly affected by these treatments. We conclude that MT or TRP added to omeprazole treatment, significantly accelerates healing rate of H. pylori infected chronic gastroduodenal ulcers over that obtained with omeprazole alone and this likely depends upon the significant rise in plasma MT and possibly also in leptin levels, both hormones involved in the mechanism of gastroprotection and ulcer healing.

Prevalence of spontaneous bacterial peritonitis in asymptomatic inpatients with decompensated liver cirrhosis - a pilot study.

PURPOSE: To assess the prevalence of spontaneous bacterial peritonitis (SBP) in asymptomatic patients with decompensated liver cirrhosis. MATERIAL AND METHODS: Patients (pts) with symptoms of decompensation of liver cirrhosis, ascites, and no signs indicating SBP were included to our study. Exclusion criteria include: 1/ clinical symptoms of infection, 2/ developing de novo or worsening hepatic encephalopathy, 3/ gastrointestinal bleeding within the last month, 4/ renal failure, 5/ antibiotic treatment or norfloxacin prophylaxis at admission. About 60 ml of ascitic fluid were drawn for lab examination. Pathologic assessment for atypical cells was also performed. RESULTS: 37 patients fulfilled inclusion criteria. Their mean age was 56.2 ± 12.1. The Child-Pugh classification revealed 13 (35.1%) patients of class B and 24 (64.9%) patients of class C. The mean Model for End-Stage Liver Disease score in this group was 16.6 ± 6.8. The mean ascitic protein content was 1.85 ± 1.09 g/dL and mean neutrophil count 144.8 ± 445.1/mm3. Ascitic fluid analysis revealed: signs of bacterascites in 6 of 37 (16.2%) pts; neutrocytic ascites in 1 of 37 (2.7%) pts; and 2 of 37 (5.4%) pts met criteria for SBP. C-reactive protein level was the best predictor of infection [SBP(+) 47.9 ± 40.9 versus SBP(-) 11.7 ± 5.1; p= 0.0005]. CONCLUSIONS: The prevalence of SBP in asymptomatic cirrhotics with ascites is low. We observed the trend towards more frequent occurrence of the infection in patients suffered from severe liver disease (Child-Pugh C group).

The effects of L-tryptophan and melatonin on selected biochemical parameters in patients with steatohepatitis.

Nonalcoholic fatty liver disease is the most common chronic liver disease and nonalcocholic steatohepatitis (NASH) is its advanced form. Oxidative stress and hepatocyte apoptosis may be involved in pathogenesis of NASH and particularly in progress of NASH to liver fibrosis and cirrhosis, which are initiated by the inflammation and which promote the progress of the disease. The aim of this study was to evaluate the effects of melatonin and L-tryptophan on selected biochemical parameters of blood in patients with NASH. Forty five patients with NASH, confirmed by histopathological examination of liver biopsy samples, were admitted to the study. They were divided into three groups (I, II and III). The first group (group I, n=15) received preparation Essentiale forte 3 times a day and tryptophan 500 mg twice daily for 4 weeks. In the second group (group II, n=15), Essentiale forte three times a day was administered with melatonin 5 mg applied twice a day for 4 weeks. The third group (group III, n=15) received only Essentiale forte with placebo three times a day for 4 weeks. After four-week treatment we found statistically significant reduction in GGTP, triglycerides and proinflammatory cytokine levels in the melatonin-treated (group I) and the L-tryptophan-treated patients (group II). Plasma level of melatonin was significantly elevated in groups treated with tryptophan (group I) and melatonin (group II), but remained unchanged in placebo-treated group (group III). Among patients from the third group (treated with placebo) no statistically significant differences in the measured biochemical parameters were observed. The present study suggests that melatonin and tryptophan have the significant impact on the reduction in plasma levels of proinflammatory cytokines and may be useful in the treatment of patients with NASH.

Role of melatonin in mucosal gastroprotection against aspirin-induced gastric lesions in humans.

Melatonin and its precursor, l-tryptophan, have been shown to exert gastroprotective effects in animals, but their influence on the gastric damage by aspirin (ASA) in humans has been sparingly investigated. In this study, we designed to determine the effects of melatonin and l-tryptophan on ASA-induced gastric mucosal damage, gastric microbleeding, mucosal generation of prostaglandin E(2), and plasma melatonin, and gastrin levels. Three groups of healthy male volunteers (n = 30) with intact gastric mucosa received daily for 11 days either ASA alone or that combined with melatonin or tryptophan. Gastric blood loss and mucosal damage were evaluated at 3rd, 7th, and 11th days of ASA administration by endoscopy using Lanza score. ASA alone caused a marked rise of gastric damage and gastric blood loss, mainly at day 3rd and 7th, but they were significantly reduced at 11th day. Pretreatment with melatonin or tryptophan remarkably reduced ASA induced gastric lesions and microbleeding. Gastric mucosal generation of PGE(2) was suppressed by about 90% in all subjects treated with ASA alone without or with addition of melatonin or tryptophan. Plasma melatonin was markedly increased after treatment with melatonin or tryptophan plus ASA, but it was also raised significantly after application of ASA alone. Plasma gastrin levels were raised in subjects given melatonin or tryptophan plus ASA, but not in those with ASA alone. We conclude that melatonin and its precursor tryptophan given orally significantly reduce gastric lesions induced by ASA possibly due to (a) direct gastroprotective action of exogenous melatonin or that generated from tryptophan and (b) gastrin released from the gastric mucosa by melatonin or tryptophan.

Genetic polymorphism of alcohol-metabolizing enzyme and alcohol dependence in Polish men.

Alcohol dependence poses a serious medical and sociological problem. It is influenced by multiple environmental and genetic factors, which may determine differences in alcohol metabolism. Genetic polymorphism of the enzymes involved in alcohol metabolism is highly ethnically and race dependent. The purpose of this study was to investigate the differences, if present, in the allele and genotype frequency of alcohol dehydrogenase 1B (ADH1B), ADH1C and the microsomal ethanol-oxidizing system (MEOS/CYP2E1) between alcohol-dependent individuals and controls and also to determine if these genotypes cause a difference in the age at which the patients become alcohol dependent. The allele and genotype frequencies of ADH1B, ADH1C, and CYP2E1 were determined in 204 alcohol dependent men and 172 healthy volunteers who do not drink alcohol (control group). Genotyping was performed by PCR-RFLP methods on white cell DNA. ADH1B*1 (99.3%) and ADH1C*1 (62.5%) alleles and ADH1B*1/*1 (N = 201) and ADH1C*1/*1 (N = 85) genotypes were statistically more frequent among alcohol-dependent subjects than among controls (99.3 and 62.5%, N = 201 and 85 vs 94.5 and 40.7%, N = 153 and 32, respectively). Differences in the CYP2E1 allele and genotype distribution between groups were not significant. The persons with ADH1C*1/*1 and CYP2E1*c1/*c2 genotypes became alcohol dependent at a considerably younger age than the subjects with ADH1C*1/*2, ADH1C*2/*2 and CYP2E1*c1/*c1 genotypes (28.08, 25.67 years vs 36.0, 45.05, 34.45 years, respectively). In the Polish men examined, ADH1C*1 and ADH1B*1 alleles and ADH1C*1/*1 and ADH1B*1/*1 genotypes favor alcohol dependence. The ADH1B*2 allele may protect from alcohol dependence. However, subjects with ADH1C*1/*1 and CYP2E1*c1/*c2 genotypes become alcohol dependent at a considerably younger age than the subjects with ADH1C*1/*2, ADH1C*2/*2 and CYP2E1*c1/*c1 genotypes.

Influence of the peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, rosiglitazone and antagonist, biphenol-A-diglicydyl ether (BADGE) on the course of inflammation in the experimental model of colitis in rats.

PPAR-γ plays a role in the development of immune response, particularly in inflammation. The inflammatory reaction may be stimulated or suppressed by the presence of PPAR ligands. Some researchers suggest positive influence of the PPAR-γ agonist on suppression of the intestinal inflammatory process, yet there has not been much evidence showing that the antagonist of PPAR-γ can affect the inflammatory process. The aim of the present study was to define the mechanism by which PPAR-γ ligands affect the course of experimentally induced colitis in rats. Colitis was induced in rats by rectal administration of TNBS (trinitrobenzene sulfonate). Rosiglitazone was administrated to animals at the dose of 8 mg/kg four times via an intra-gastric probe. Biphenol-A-diglicydyl ether (BADGE) was administrated intraperitoneally at the dose of 120 mg/kg, three times every second day. One group of animals received rosiglitazone together with BADGE before the induction of inflammation. Histological and ELISA examinations of large intestine samples were performed. Levels of IL-1ß, IL-6, TNF-α cytokines were determined in serum and homogenates. Rats exposed to rosiglitazone had higher body weight yet lower large intestine weight. Histological findings showed less ulceration, lower expression of crypts' loss and smaller oedema. Animals, which did not receive rosiglitazone, and those receiving it together with BADGE, developed more severe inflammatory changes. Rosiglitazone decreased the expression of inflammatory cytokines, such as IL-6 and TNF-α, both in serum and in intestinal homogenates. BADGE used with TNBS did not increase the expression of inflammatory cytokines; however, applied together with rosiglitazone, it caused inflammation similar to that observed among rats with experimentally induced colitis. Rosiglitazone reduces inflammation by decreasing the expression of IL-6 and TNF-α. BADGE administered with rosiglitazone blocks the activity of PPAR-γ and abolishes the protective effects of PPAR-γ agonist.

Altered basal and postprandial plasma melatonin, gastrin, ghrelin, leptin and insulin in patients with liver cirrhosis and portal hypertension without and with oral administration of melatonin or tryptophan.

This investigation was designed to assess the effects of oral administration of melatonin (10 mg) and tryptophan (Trp) (500 mg) on fasting and postprandial plasma levels of melatonin, gastrin, ghrelin, leptin and insulin in 10 healthy controls and in age-matched patients with liver cirrhosis (LC) and portal hypertension. Fasting plasma melatonin levels in LC patients were about five times higher (102 +/- 15 pg/mL) than in healthy controls (22 +/- 3 pg/mL). These levels significantly increased postprandially in LC patients, but significantly less so in controls. Treatment with melatonin or L-Trp resulted in a further significant rise in plasma melatonin, both under fasting and postprandial conditions, particularly in LC patients. Moreover, plasma gastrin, ghrelin, leptin and insulin levels under fasting and postprandial conditions were significantly higher in LC subjects than in healthy controls and they further rose significantly after oral application of melatonin or Trp. This study shows that: (a) patients with LC and portal hypertension exhibit significantly higher fasting and postprandial plasma melatonin levels than healthy subjects; (b) plasma ghrelin, both in LC and healthy controls reach the highest values under fasting conditions, but decline postprandially, especially after oral application of melatonin or Trp; and (c) plasma melatonin, gastrin, ghrelin and insulin levels are altered significantly in LC patients with portal hypertension compared with that in healthy controls possibly due to their portal systemic shunting and decreased liver degradation.

[Degree of nicotine dependence in the Gastroenterology Ward of Clinical Hospital number 4 in Lublin]. / Stopien uzaleznienia od nikotyny pacjentów hospitalizowanych w Oddziale Gastroenterologii SPSK 4 w Lublinie.

It is common knowledge that smoking badly influences people's health. Amount of toxic chemical substances delivered to the human organism is directly proportional to the number of smoked cigarettes. Tobacco smoking increases the number of ill people and accelerates death. The problem of nicotine addiction has both social and medical aspects. The aim of the work was to assess the tobacco smoking among patients hospitalized in the Gastroenterology Clinic in SPSK 4 in Lublin. We found that smoking prevalence in the investigated group considerably exceeds the average values for Polish population.

Melatonin and its precursor L-tryptophan prevent acute gastric mucosal damage induced by aspirin in humans.

Melatonin (MT) and its precursor L-tryptophan (Trp) are implicated in the protection of gastric mucosa against noxious agents. However, the role of MT and Trp on the gastric mucosal injury induced by aspirin (ASA) in human has not been investigated. Studies in animals showed that both MT and Trp given intragastrically prevents the formation of gastric mucosal lesions induced by ASA. The aim of the present study was to determine the influence of MT and Trp given orally to healthy humans on gastric mucosal lesions induced by ASA. The present study included 21 healthy, Hp-negative male volunteers with intact gastro-duodenal mucosa aging 20-50 yr. They were divided in 3 groups; group 1: 7 volunteers receiving daily 2 x 1g ASA (Polfa, Rzeszow) during 11 days; group 2: 7 healthy volunteers receiving 2x1 g ASA and MT (Lekam, Zakroczyn) (5 mg 30 min prior to ASA) during 11 days and group 3: 7 healthy volunteers receiving 2x1 g ASA and Trp (Ardeytropin, Germany) (0.5 g 30 min prior to ASA) during 11 days. Mucosal damage was evaluated at 3(rd), 7(th) and 11(th) days of ASA administration by endoscopy using Lanza score. Plasma melatonin was measured using RIA and gastric mucosal generation of PGE(2) was assessed also by RIA. ASA caused marked mucosal injury at all days of its administration except day 11(th) when only moderate lesions were evident. Pretreatment with MT or Trp alone was accompanied by a significant decrease in gastric mucosal lesion score. Gastric mucosal generation of PGE(2) was suppressed by about 90% in subjects treated with ASA without or with MT or Trp. We concluded that: MT and its precursor Trp significantly attenuate gastric mucosal lesions induced by aspirin. The action of Trp may be be mediated by MT produced in gastrointestinal tract from Trp. The gastroprotective action of MT and Trp is independent on gastric mucosal PGE2 generation.

Non-variceal upper gastrointestinal bleeding--guidelines on management.

In gastroenterology non-variceal upper gastrointestinal bleeding is health hazard. Frequency of occurrence accounts for 40-150 cases per 100000 inhabitants with death rate of 7-14%. Researches which goal is to improve treatment effectiveness as well as to establish standardized procedures for managing patients with symptoms of non-variceal upper gastrointestinal bleeding; have been conducted since many years. At the moment of admission, designed standards enable appropriate elaboration of patients' health state, referral to the right clinic and implementation of the most accurate treatment methods. Increase of suppression of primary bleeding as well as prevention of recurrence is associated with dynamic development of endoscopic treatment methods as well as with optimization of pharmacological treatment. In significant percentage, efficiency of non - variceal bleedings treatment depends on clinic's character (availability of equipment, experience of personnel) and on cooperation between several specialists (including gastroenterologist, surgeon, anesthetist, operative radiologist). Aim of the work is to present the latest evaluation of the mentioned subject, based on accessible literature. This work includes the basic principles for determination of bleeding intensity and risk of its recurrence as well as directions referring to fluids resuscitation and to monitoring of patients. Information on currently applied endoscopic methods for inhibition of non variceal upper gastrointestinal bleeding (injection, mechanical and thermo-coagulation techniques), comparison of their efficiency and possibility of application is provided in the work. The paper work also presents the newest directives for pharmacological treatment and guidelines for possible surgical treatment.

Pathophysiology of portal hypertension.

In last years significant progress in recognizing mechanisms of portal hypertension pathophysiology was done. However, some unclear topics in this disease still exist. Portal hypertension is primarily caused by the increase in resistance to portal outflow and secondly by an increase in splanchnic blood flow. Portal hypertension is associated with changes in the intrahepatic, systemic, and portosystemic collateral circulation. Alterations in vasoreactivity (vasodilation and vasoconstriction) play a central role in the pathophysiology of portal hypertension by contributing to increased intrahepatic resistance, hyperdynamic circulation, and expansion of the collateral circulation. Among vasoactive substances which are activated in portal hypertension nitric oxide (NO) is considered as the most important vasodilator. Endothelin-1 and cyclooxygenase-derived prostaglandins are the main vasoconstrictor factors. The imbalance between the hyperresponsiveness and overproduction of vasoconstrictors and the hyporesponsiveness and impaired production of vasodilators are the mechanisms responsible of the increased vascular one in the sinusoidal area of the liver. New concepts in the pathophysiology of portal hypertension find the significant role of hepatic stellate cells activated by endothelial factors which cause vascular remodeling as an adaptive response of the portal vessels wall. The most frequent causes of portal hypertension include portal vein thrombosis, storage diseases of the liver, hepatic cirrhosis (independent of etiology), hepatic veins thrombosis and schistosomiasis. Understanding the pathophysiology of portal hypertension could be of great utility in preventing and curing the complications of portal hypertension, such as esophageal varices, hepatic encephalopathy, ascites.

Modern methods of endoscopic diagnosis of gastrointestinal tract.

The last years brought the substantial development of new diagnostic procedures of gastrointestinal tract. High resolution endoscopy and magnifying endoscopy both give the detailed picture of the mucosal surface of esophagus, stomach, duodenum and large bowel. They are very useful in diagnosis precancer states or early cancer. The use of the biopsy forceps and cytology brush allows histologic confirmation of endoscopic impression. The new methods, which allow complete diagnosis of small bowel are double balloon enteroscopy and capsule endoscopy. They are recommended in case of Crohn's disease, identification of bleeding source, detection of stenoses and neoplastic changes in the small intestine, diagnosis of chronic diarrhea and detection of visceral diseases or malabsorption syndromes. Only double balloon enteroscopy allows to take the biopsy as well as to make endoscopic therapy. Chromoendoscopy involves topical application of stains to the mucosa on endoscopy in order to delineate and better characterize specific findings. This technique is thought to be helpful for both the diagnosis of early cancer for evaluation of non-neoplastic diseases. Endoscopic ultrasonography connecting endoscopic and ultrasonographic techniques is applied to diagnose the intramural abnormalities.

Therapeutic endoscopy in gastroenterology.

The role of therapeutic endoscopy in current gastroenterology is very important. Therapuetic endoscopy is useful in treatment of gastrointestinal bleeding. Endoscopic control of gastrointestinal bleeding includes the following procedures of haemostasis techniques: photocoagulation, electrocoagulation, thermocoagulation and injection method. Owing to these procedures mortality has significantly decreased. Endoscopic hemostasis eliminates the risk of surgery, is less expensive and better tolerated by patients. Colonoscopic polypectomy is a widely used technique. By removal of polyps the incidence of colon cancer can be decreased. The "hot biopsy" forceps can be used to excise polyps of up to 6 mm. Larger polyps can be removed safely by snare electrocautery and retrieved for histologic study. Endoscopic retrograde cholangiopancreatography has a therapeutic application designed to cut the sphincter of Oddi fibers of the distal common bile duct, what is indicated currently in choledocholithiasis and papillary stenosis with ascending cholangitis, acute gallstone pancreatitis. Endoscopic sphincterotomy in now an established procedure that is indicated in patients with common bile duct calculi. Endoscopic decompression of the biliary tree - dilatation benign structures of the biliary tree with baloon catheters and placement an internal endoprothesis allows the nonoperative decompression and significant palliation for patients with obstructing tumors.

Genetic polymorphism of alcohol dehydrogenase 3 in digestive tract alcohol damage.

BACKGROUND/AIMS: Genetic polymorphism of enzymes involved in alcohol metabolism plays a relevant role in etiopathogenesis of alcohol disease. The aim of the present study was to find in the Polish population the ADH3 genotypes, which are likely to be responsible for higher susceptibility to alcohol disease of the liver and chronic alcohol pancreatitis. METHODOLOGY: The ADH3 genotype and ADH3*1 and ADH3*2 alleles frequency were examined in 266 patients. Genotyping of the ADH3 was performed using polymerase chain reaction-restriction fragment length polymorphism methods on white cell DNA. RESULTS: The genotype ADH3*1/ADH3*1 was found to be significantly more frequent in alcohol abusers compared to non-drinkers. The examinations of the group of alcohol abusers showed that the genotype ADH3*2/ADH3*2 occurred statistically significantly less frequently in patients with chronic pancreatitis than those without alimentary lesions and patients with cirrhosis. Thus it is likely to be the protective factor of chronic pancreatitis. CONCLUSIONS: The alleles ADH3*1 and genotype ADH3*1/ADH3*1 were significantly more frequent in men than in women, while alleles ADH3*2 and genotype ADH3*2/ADH3*2 were more common in women. This may account for rarer alcohol addiction observed in Polish women.

The role of adenosine A2a receptors in experimental acute pancreatitis.

PURPOSE: The role of adenosine and its receptors in acute pancreatitis remains unelucidated. The aim was to evaluate the effects of the adenosine A2a receptor agonist and antagonist in the severe, taurocholate-induced experimental acute pancreatitis (EAP). MATERIAL AND METHODS: The experiments were performed on 80 male Wistar rats, subdivided into 4 groups: C--the control rats, I--the EAP group, IIA--EAP group treated with the A2a adenosine receptor agonist CGS 21680, IIB--EAP group treated with the A2a adenosine receptor antagonist ZM 241385. The blood for alpha-amylase and lipase and tissues samples for the morphological examinations and immunohistochemistry for A2a receptors were collected in 2, 6, 24 hours of the experiment. RESULTS: The serum alpha-amylase tended to decrease in the group IIA as compared to EAP untreated after 6 and 24 h. No significant effect of both treatments on serum lipase was noted. The administration of CGS 21680 resulted in favorable decrease of the inflammatory cell infiltration, hemorrhagic changes, necrosis and vacuolization of acinar cells, without an evident effect on the edema of the interstitial tissue. The administration of ZM 241385 did not affect the scores of necro-hemorrhagic changes and inflammatory infiltration, whereas it decreased the scores of vacuolization and edema. In all groups the expression of A2a receptors was similar. CONCLUSIONS: Our findings suggest, that A2a adenosine receptors are involved in the course of sodium taurocholate EAP. It is probable that the modulation of some subgroups of adenosine receptors could alleviate the course of severe experimental AP.

Level of serum cytokines in biliary gastritis and erosive gastritis with Helicobacter pylori coinfection.

The aim of this study was evaluation of serum cytokines level in patients with biliary and erosive gastritis. 50 patients were admitted to this study: 20 with biliary, 20 with erosive gastritis and 10 as the control group. In all patients serum levels of Il-8, Il-6R, Il-2R were evaluated. In each group half patients were infected by Helicobacter pylori, and the second half were uninfected. Mean level of Il-8 in patients with biliary gastritis was higher than in those in the control group, and was more increased in Helicobacter pylori infected patients than in uninfected ones. In erosive gastritis accompanied by Helicobacter pylori infection mean level of Il-8 was higher than in uninfected patients for which the level was normal. Serum Il-6R levels in biliary gastritis with infection by Helicobacter pylori were higher than in biliary gastritis without infection. These values were statistically significant vs. the control group. In erosive gastritis accompanied by Helicobacter pylori mean level of Il-6R was higher than in the control group, but was normal in patients without Helicobacter pylori. We noticed no influence of Helicobacter pylori infection on Il-2R levels in patients with biliary gastritis and erosive gastritis. These levels were normal in all groups of patients. In conclusion, in biliary gastritis we found the levels of Il-8, Il-6R higher than in erosive gastritis. Particularly significantly high levels of Il-8, Il-6R were observed in gastritis accompanied by Helicobacter pylori infection.

The influence of nifedipine (calcium channel blocker) and Bay-K-8644 (calcium channel agonist) on the development of experimental acute pancreatitis.

The aim of this paper was to evaluate the influence of nifedipine (calcium channel blocker) and Bay-K-8644 (calcium channel agonist) on cerulein acute pancreatitis (AP) in rats. AP was induced according to the Lampel and Kern method (1) by the continuous intravenous infusion of cerulein in the doses of 5 x 10(-6) g/kg/h for 12 hours. There was obtained a statistically significant decrease in serum amylase activity and pancreatic weight in the groups treated with higher doses of nifedipine before infusion of the cerulein compared with rats treated only with cerulein. However, in the group treated with Bay-K-8644 before infusion of cerulein statistically significant increase was obtained in serum amylase activity and pancreatic weight compared with the group treated only with cerulein. The investigations suggest a beneficial effect of higher doses of nifedipine on cerulein induced AP. The inflammatory changes in the pancreas in the groups treated with nifedipine observed under the light microscope were smaller than in the group treated only with cerulein.

The effect of caerulein-induced acute pancreatitis on the levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in various rat tissues.

The effects of caerulein-induced acute pancreatitis (AP) on the levels of 5-HT and 5-HIAA in pancreas, liver, brain, kidney and different parts of the digestive tract in rats have been studied. The acute pancreatitis was induced by the continuous intravenous infusion of caerulein in the doses of 5 x 10(-6) g/kg/h and 7.5 x 10(-6) g/kg/h for 12 hours, and the 5-HT and 5-HIAA concentrations were determined by the method of Curzon and Green. The changes evoked by caerulein varied qualitatively and quantitatively between organs. The significant decrease of both 5-HT and 5-HIAA was observed in pancreas, liver, brain and kidney while in the stomach there was a significant fall of 5-HT level accompanied by the relevant increase of 5-HIAA level. In the duodenum, an opposite effect was noticed, the level of 5-HT was higher than normal whereas the 5-HIAA level was reduced. The significant decrease of the 5-HT and 5-HIAA levels in pancreas observed in the present study suggests the importance of 5-HT in the development of acute pancreatitis.