Długosz J

Severity of Helicobacter-induced gastric injury correlates with gastric juice ammonia

We postulated that ammonia produced byHelicobacter pylori may contribute to gastric mucosal injury. This hypothesis was evaluated inHelicobacter-positive patients with chronic renal failure in whom a high urea concentration might amplify this phenomenon. Gastric urea and ammonia were measured, and the severity of gastritis was evaluated by counting mononuclear and polymorphonuclear, cells. High gastric ammonia and low urea inHelicobacter-positive patients, and the converse inHelicobacter-negative subjects, were observed. There was a significant correlation between gastric ammonia and interstitial polymorphonuclear leukocytes infiltration (P<0.05), suggesting a causal link. Eradication ofHelicobacter pylori was associated with a decrease of ammonia and an increase of urea (P<0.01). The significant correlation between the severity of gastric inflammation and the gastric juice ammonia concentration suggests that ammonia may play a pathogenic role inHelicobacter-associated gastric injury.

Nutritional status of patients hospitalised in Poland

Aim:Screening and extended assessment of the nutritional status of patients on admission and on discharge from hospital were carried out.Description:The studies were carried out in four teaching hospitals, four provincial hospitals and four county hospitals in Poland.Subjects:Screening examinations were carried out for 3310 randomly selected patients (every 10th patient admitted to hospital, including 1916 female cases aged from 16 to 92 y and 1394 male patients aged from 16 to 100 y). Extended examinations were carried out on 210 patients aged from 16 to 87 y (including 122 female and 88 male).Main assessment parameters:Anthropometric (height, weight, body mass index (BMI), waist-to-hip ratio (WHR), arm circumference) and biochemical indices (erythrocyte count, haemoglobin concentration, white blood cell count, blood lymphocyte count and serum albumin serum concentration). The extended examinations included determination of antioxidant vitamins (A, C, E), vitamin B12 and folic acid.Results:On admission to hospital, 10.43% of the patients surveyed had a BMI below 20 kg/m2, in 20.74% of patients serum albumin concentration was below 3.5 g/dl, indicating possible protein energy malnutrition. In addition, 21.02% had lymphocyte count below 1.5 × 103/mm3. During hospitalisation, deterioration in the nutritional status of the patient population occurred. On discharge from hospital, the percentage of patients with BMI<20 kg/m2 increased to 11.21% and the percentage with low blood albumin (<3.5 g/dl) increased to 28.57%. On admission, vitamin C deficiency was present in 51.8% of patients, folic acid deficiency in 32%, vitamin E deficiency in 10%, vitamin B12 deficiency in 6.8% and vitamin A deficiency in 1.4%. Vitamin deficiencies were present equally in malnourished, overweight and obese patients.Conclusions:In patients admitted to hospitals in Poland, malnutrition risk demonstrated by BMI was observed in 10.43% of patients. On the basis of biochemical indices, increased nutritional risk was demonstrated in 21% of patients. Vitamin malnutrition was seen in the majority of patients. A significant correlation between weight, BMI, arm circumference, blood lymphocyte count and the number of days spent in hospital was observed.Sponsorship:The Committee of Scientific Research and the Ministry of Health—PBZ 012-14.

Feedback regulation of stimulated pancreatic enzyme secretion during intraduodenal perfusion of trypsin in man

Abstract. The pancreatic enzyme secretion in several species is controlled by a negative feedback mechanism induced by the presence of active proteases in the duodenum. The existence of this mechanism in man is controversial. The purpose of the present study was to evaluate the effect of tryptic activity in the duodenum on phenylalanine‐stimulated pancreatic enzyme secretion in healthy volunteers. A double‐balloon, multilumen tube was used for the collection of duodenal juice containing pancreatic enzymes. The continuous infusion of phenylalanine (100 mM) into the duodenum evoked an almost constant secretion of trypsin, amylase and lipase for 160 min. The infusion of trypsin (150 mg h‐1; 1·25 g l‐1) caused a reduction of phenylalanine‐stimulated amylase and lipase output by 25%. The subsequent infusion of aprotinin at a dose of 1·5 × 106 KIU for 30 min led to an almost complete inhibiton of trypsin. Simultaneously, the amylase and lipase output returned to the values seen before trypsin perfusion. Infusion of a higher dose of trypsin (300 mg h‐1; 2·5 g l‐1) caused a more pronounced decrease in phenylalanine‐stimulated amylase and lipase output by 45%. These data indicate that active trypsin in the duodenum is responsible for the inhibition of phenylalanine‐stimulated pancreatic enzyme secretion in man in a dose‐dependent fashion, thus confirming the existence of a feedback control of pancreatic secretion regulated by the amount of proteases in the gut.

Seroprevalence of Helicobacter pylori infection in Polish children and adults depending on socioeconomic status and living conditions

PURPOSE Helicobacter pylori (H. pylori) is one of the causes of gastritis, peptic ulcer disease, gastric cancer and MALT-lymphoma. The frequency of H. pylori infection is different in various regions of the world and dependent on age, socioeconomic and hygiene status. The objective of this study was to assess seroprevalence and the associated socioeconomic and sociodemographic characteristics influencing H. pylori infection in children and adults in Polish population. MATERIAL/METHODS In multicenter epidemiological studies, H. pylori infection occurrence was assessed in Poland in the years 2002 and 2003. The seroprevalence of H. pylori infection diagnosis was based on IgG anti-H. pylori antibodies concentration above 24 UI/ml, which was measured using ELISA test. The study included 6565 subjects: 3307 adults (50.37%) and 3258 children (49.63%). RESULTS Positive result was observed in 3827 subjects (58.29%), i.e. 1043 children (32.01%) and 2784 adults (84.19%). H. pylori infection prevalence was greater in children of poor economic status, who were born in a rural area, lived in crowded houses with no running tap water and with toilet outside the house, and who did not observe hygiene rules. In adults, the factors predisposing to higher probability of being H. pylori infected included: being born in a rural area, having low family income and elementary education, smoking tobacco, drinking high proof alcohols as well as not observing of hygiene rules. CONCLUSIONS Improvement of socioeconomic status, sanitary and hygienic conditions and the education of the society might decrease H. pylori infection prevalence in children and in adults.

Lysosomal activity of pulmonary alveolar macro phages in acute experimental pancreatitis in rats with reference to positive PAF-antagonist (BN 52021) effect

The activation of pulmonary alveolar macrophages (PAMs), might play an important role in severe complications of acute pancreatitis. The aim of our study was to assess the labilization of macrophage lysosomal membranes and release of lysosomal cathepsin B (CB) and N-acetyl-beta-D-hexosaminidase (NAH) into bronchoalveolar lavage fluid (BALF) during taurocholate acute pancreatitis (AP) in rats treated with PAF-antagonist--BN 52021. Total activity of CB increased by 374% after 6 h and by 237% after 12 h of AP in lysosomal enriched fraction of PAMs. Fractional free activity of CB increased to 40% after 6 h and to 38% after 12 h of AP. Free activity of CB was increased 5 fold in the supernatant of macrophage homogenate, and 10 fold in the supernatant of BALF after 6 h of AP. The values of NAH activity roughly paralleled that of CB. Treatment with BN 52021 (5 mg x kg(-1) every 6 h i.v.) partially normalized the measured parameters. Our results indicate that the PAF-antagonist BN 52021 reduced the increase of total and free activity of lysosomal hydrolases of PAMs and partly prevented the labilization of their lysosomal membranes. Therefore, an important mechanism of BN 52021 beneficial effect in pulmonary complications of acute pancreatitis could be dependent on the stabilization of PAMs lysosomes.

The effect of the prostaglandin analogue - misoprostol on rat liver mitochondria after chronic alcohol feeding☆

Rats fed ethanol (36% of total calories in a nutritionally adequate liquid diet) for 5 weeks develop functional alterations of hepatic mitochondria and steatosis of the liver. At the fatty liver stage, ADP-stimulated respiration of mitochondria was depressed in ethanol fed rats by 30% (p less than 0.001) with glutamate + malate and by 23% (p less than 0.001) with succinate as substrates. A similar decrease was noted in the respiratory control ratio (RCR) (34% and 29%, respectively). The total lipid content of the liver increased 2.6 fold (p less than 0.001). Mitochondrial dysfunction could be prevented, in part, by the treatment with a synthetic derivative of prostaglandin E1, misoprostol, at a mean daily dose of 80 micrograms/kg of body weight. The RCR with glutamate + malate as substrates was improved by 36% (p less than 0.05). We conclude that misoprostol attenuates several functional alterations in liver mitochondria during alcohol feeding.

The endothelin‐1 receptor antagonists ameliorate histology and ultrastructural alterations in the pancreas and decrease trypsinogen activation in severe taurocholate pancreatitis in rats

Summary.  The role of potent vasoconstrictor endothelin‐1 (ET‐1) in acute pancreatitis (AP) remains controversial. The aim was to compare the effect of nonselective ET RA/B (LU‐302872) and selective ET RA (LU‐302146) antagonists on pancreatic histology, ultrastructure and trypsinogen activation in severe taurocholate AP in rats. Male Wistar rats with AP were treated with an intraperitoneous injection of 1, 5 and 10 mg/kg of body weight of each antagonist at 0, 6, 12 and 18 h after taurocholate administration. After 24 h, the samples of pancreases were taken for histological and ultrastructural examinations and for assessment of trypsinogen activation. Both antagonists, at all investigated doses, decreased the damage to the acinar cells detected in the light microscope and ultrastructurally. Trypsinogen activation increased to 29.7 ± 3.9% in the AP untreated in comparison to the control group [12.7 ± 1.4% (P < 0.001)]. This increase was attenuated to 13.8 ± 2.2% in AP treated with a high dose of the nonselective antagonist and to 8.4 ± 1.7% with low dose of selective antagonist. The obtained results indicate that ET‐1 could participate in the damage to the pancreas during AP. Both antagonists of ET‐1 receptors exerted a similar beneficial effect on the morphological changes of the pancreas in AP. One of the probable mechanism could be the attenuation of trypsinogen activation.

Cathepsin B inhibition in two models of acute pancreatitis

SummaryThe possible role of cathepsin B in the pathogenesis of two forms of acute pancreatitis was studied using the cathepsin B inhibitor known as E-64. In an edematous, nonfatal pancreatitis induced by supramaximal doses of cerulein, increases in the serum amylase and lipase levels were less pronounced in rats pretreated with E-64. Other parameters of pancreatic injury were unaffected by inhibition of cathepsin B. In a necrohemorrhagic type of pancreatic injury induced by retrograde infusion of bile salts into the pancreatic duct, E-64 partially attenuated increases in serum levels of amylase and lipase, and in addition, reduced the activation of trypsinogen. However, the high mortality in this model of pancreatitis was not modified.

The functional and ultrastructural changes of hepatic mitochondria in acute experimental pancreatitis in dogs treated with prostacyclin.

Summary Acute pancreatitis affects the subcellular status of the liver both by enzymatic toxemia and by the impairment of the protective function exerted by a normal pancreas on the liver. The aim of this study was to investigate the effect of the cytoprotective agent prostacyclin (PGI2) on hepatic mitochondria during acute experimental pancreatitis (AEP) in dogs. AEP was induced by the injection of a bile and trypsin mixture into the pancreatic duct, and experiments were terminated after 12 hrs with the exception of dogs with AEP 24 hrs (N = 5). The hepatic mitochondria from the group with AEP 12 hrs without treatment (N = 5) showed a significant impairment of succinate oxidation in St. 3 (with ADP) to 20.1 nanoatoms O×min−1× mg−1 of mitochondrial protein in comparison to healthy dogs (N = 4) −37.6 units. The respiratory control ratio (RCR) in the former group was half as great as in the control group (1.56 and 3.13 respectively). The ADP: 0 ratio in this group was impossible to calculate. DNP-stimulated ATP-ase activity was lowered to 50.6 nM Pi min−1mg−1 of protein in comparison to the healthy animals (642.7 units). In dogs AEP 12 hrs treated with PGI2 in the dose of 20 ng/kg · min for 12 hrs (N = 5) and in the group additionally pretreated with PGI2 for 1 hr before AEP (N = 5), the respective values of succinate oxidation in St. 3 were 22.2 and 26.5 units; RCR with ADP 2.05 and 2.07; ADP: O ratio 1.10 and 1.19 (in healthy dogs ADP: O = 1.90). DNP-stimulated ATP-ase activity was also augmented in comparison with the untreated group, 94.0 and 125.6 units, respectively. In the group with AEP 12 hrs without treatment, the ultrastructural examination of the liver showed severely damaged, mitochondria with swelling, destruction of limiting membranes and cristae. In the group with AEP 24 hrs without treatment the functional and morphological picture of mitochondria was improved in comparison to AEP 12 hrs and was comparable to treated groups. Prostacyclin in investigated dosage exerts a protective effect on hepatic mitochondria, damaged during acute experimental pancreatitis in dogs.

Beneficial effect of iloprost on the course of acute taurocholate pancreatitis in rats and its limitation by antecedent acute ethanol intake.

The effects of stable prostacyclin analogue iloprost on the trypsinogen activation, labilization of lysosomal membranes, lipolytic enzymes activities, histopathological and ultrastructural changes in the pancreas of rats with severe, taurocholate acute pancreatitis (AP), preceded for 6 h by acute ethanol intake have been investigated. Iloprost (1 microg/kg b.w., i.p.) was applied every 6 hours after inducing of taurocholate AP. The antecedent intragastric 40% ethanol intake (5 g/kg b.w.) increased an index of trypsinogen activation in AP lasting 18 h. Treatment with iloprost prevented this increase in the rats with AP given earlier alcohol, and limited the labilization of lysosomal membranes in nonalcoholized rats with AP. Phospholipase A2 and lipase activities were reduced by iloprost only in the rats not given ethanol. The additional damaging effect of acute ethanol abuse prior to AP could be dependent on augmented activation of trypsinogen. The protective effect of iloprost in AP seems to be dependent on the attenuation of trypsinogen activation, decrease of total potential trypsin and the decrease of lysosomal membranes labilization. Its protective effect could be limited in taurocholate acute pancreatitis preceded by acute ethanol intake as evidenced by the differences in the cathepsin B, phospholipase A2 and lipase activities and by histopathological and ultrastructural examination.