Short-chain fatty acids in the saliva of patients with gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a condition characterized by persistent symptoms and complications resulting from reflux of gastric contents into the esophagus. Short-chain fatty acids (SCFAs) are fermentation products of dietary fibres by the gut microbiota and are often studied for their anti-inflammatory and anticancer effects. The presence of SCFAs in the upper gastrointestinal tract, including in patients with GERD, has not been previously studied. The aim of this study was to investigate the relationship between the concentrations of SCFAs in the saliva of different age groups of patients with GERD. The study included 86 patients diagnosed with GERD, divided into two groups according to age: under and over 60 years of age, treated in the Gastroenterology and Hepatology Outpatient Clinic of the University Hospital in Cracow and 39 patients without gastrointestinal tract diseases. After clinical examination, blood was drawn to determine complete blood count, haemoglobin, and CRP. The oral cavity was examined, and unstimulated mixed saliva was collected. The SCFAs analysis was made by liquid chromatography-tandem mass spectrometry after facile derivatization coupled with liquid-liquid extraction. Of the six SCAFs studied, the highest median concentrations of acetic acid and propionic acid were observed in the saliva of patients with GERD and in the control group, in both the younger and older groups of patients. The concentrations of acetic acid and propionic acid were also higher compared with the four other fatty acids in the saliva of patients with GERD and in the control subjects. There were no correlations between salivary SCFAs levels and selected clinical and endoscopic parameters, including chronic inflammatory changes of the esophagus and stomach. In conclusions: SCFAs are present in the saliva of patients with GERD and in the control healthy persons. With the exception of valeric and isovaleric acids, salivary levels of SCFAs were significantly higher in patients with GERD compared to the control group. The highest concentrations of acetic acid and propionic acid were observed in patients with GERD and in both the younger and older patient groups. There were no differences in the concentrations of SCFAs in the saliva of female and male groups. We found no correlations between salivary SCFAs levels and selected clinical, laboratory and endoscopic changes of the oesophagus and stomach.

Nuclear factor-κB - importance, induction of inflammation, and effects of pharmacological modulators in Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory disease of unknown etiology that covers the entire digestive tract and occurs with periods of remission and clinical exacerbation. CD is most common in North America and Europe, but its incidence is rising rapidly in Asian countries. The pathogenesis of CD is unclear, while genetic predisposition, immune imbalance, and host-intestinal microbiota interactions are taken into account. Incorrect activation of κB nuclear factor (NF-κB) signaling pathways is associated with CD initiation and progression. NF-κB leads to excessive production of pro-inflammatory cytokines that cause a chronic inflammatory process of the intestines. It is currently believed that the NF-κB pathway plays a key role in the pathogenesis of CD, hence current treatments aim to block this pathway. Studies have shown that activation of NF-κB is reduced by treatment with, among others, mesalazine and glucocorticoids. This review presents epidemiology and pathogenesis of CD, the participation of NF-κB in this disease, as well as modern methods of treatment aimed at inhibiting NF-κB activation.

Serum galectin 3, galectin 9 and galectin 3-binding proteins in patients with active and inactive inflammatory bowel disease.

Galectins are lectins involved in physiological processes such as cell proliferation, apoptosis and migration, immune responses, inflammation, signalling, and angiogenesis. This study assessed the serum levels of galectin-3 (Gal-3) and galectin-3 (Gal-9) and galectin 3 binding protein (Gal-3BP), and evaluated their associations with the clinical characteristics and levels of inflammatory markers in patients with inflammatory bowel disease (IBD). A total of 48 patients with ulcerative colitis (UC), 77 with Crohn's disease (CD), and 30 healthy volunteers participated in the study. Complete blood counts, C-reactive protein, fibrinogen, albumin, glucose, creatinine, Gal-3, Gal-9, and Gal-3BP were measured. The median Gal-3 and Gal-9 levels did not differ between patients and controls. The median level of Gal-3BP was significantly higher in patients with CD than in controls (8084.6 (5637.8 - 11494.4) ng/ml versus 5962.2 (5280.15 - 7247.92) ng/ml, P = 0.02). No significant differences in Gal-3, Gal-9, and Gal-3BP between active and inactive CD and UC subgroups were found. The median Gal-3BP was higher in subgroups with active CD than in controls (8175.9 (5736.4 - 12871.62) ng/ml versus 5962.2 (5280.15 - 7247.92) ng/ml, P = 0.004). Our results showed that serum Gal-3 and Gal-9 should not be considered biomarkers of IBD. Despite not being a specific marker for CD, serum Gal-3BP might be used as an adjuvant biomarker for disease activity. However, further studies using a larger cohort are required to confirm its clinical usefulness.

Alterations in glutathione peroxidase and superoxide dismutase activities in plasma and saliva in relation to disease activity in patients with Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory condition with uncertain aetiology. Dysfunction of immunoregulatory factors and overproduction of reactive oxygen species (ROS) may contribute to the damage of the gastrointestinal tract. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) are involved in protection of cells from the damaging effects of ROS. The aim of the study was to assess activity of antioxidative stress enzymes, GPx and SOD, in plasma and saliva of patients with active and inactive forms of CD. Forty-seven patients with CD were prospectively enrolled in the study. The control group comprised 25 healthy volunteers. Patients' demographics, clinical features, localization of inflammatory changes, CD history, and treatment were recorded. SOD and GPx were assayed in plasma and saliva samples by ELISA method. CD activity index (CDAI) scores correlated inversely with SOD in plasma (r = - 0.46; P = 0.0012), but not in saliva. No correlations were observed in respect to GPx activities in both plasma and saliva and CDAI. Higher activity of plasma SOD was observed in patients with inactive CD in comparison with active CD (P = 0.004). No significant differences in SOD and GPx activity both in plasma and saliva were found between CD remission group and the control group. We concluded that in active CD the antioxidant defence system was diminished and returned to normal values in remission. Results of SOD and GPx assays in saliva are not conclusive, suggesting that saliva seems to be not an appropriate material for further similar studies.

Met-enkephalins in patients with inflammatory bowel diseases.

PURPOSE: Opioid peptides provide a link between the neuroendocrine and immune systems. They modify the inflammatory process through their effect on the synthesis and secretion of cytokines and on the proliferation of leukocytes to the inflammatory lesion. The evaluation analyzed changes in free met-enkephalin concentration values in the serum and colon mucosal biopsy specimens of patients with inflammatory bowel disease (IBD). MATERIAL AND METHODS: In serum and colon mucosal biopsy specimens, free met-enkephalin levels were determined in 43 patients with ulcerative colitis (UC) and 38 individuals with Crohn's disease (CD). The evaluation analyzed the effect of disease activity, inflammatory lesions of the colon and laboratory parameters, on the level of the investigated marker. The control group consisted of 45 healthy volunteers. RESULTS: Serum free met-enkephalin levels were depressed in patients with CD (85.4pg/ml) and UC (101.5pg/ml) as compared to the controls (119.4pg/ml). Met-enkephalin levels in colonic biopsies collected from inflammatory lesions in IBD patients were significantly higher as compared to sections without inflammatory lesions (6.59pg/mg vs. 2.89pg/mg, p < 0.01 in the CD group and 6.12pg/mg vs. 3.47pg/mg, p < 0.05 in the UC group) and their level correlated with disease activity. CONCLUSIONS: The present investigation is the first study that demonstrates changes in free met-enkephalin levels in IBD that may play a role in the pathogenesis and course of the disease. Further studies are necessary to assess the anti-inflammatory effect of opioid peptides.

Optimal maintenance therapy in patients with non-erosive reflux disease reporting mild reflux symptoms--a pilot study.

PURPOSE: This pilot study aimed at finding trend for further investigation of the optimal maintenance therapy with lansoprazole in patients with non-erosive reflux disease (NERD) suffering from mild symptoms. MATERIAL AND METHODS: Sixty consecutive patients with diagnosed NERD reporting mild symptoms were included in the study. After successfully finishing a four-week treatment with lansoprazole (30 mg daily), the patients were randomized into three groups administered: 1--lansoprazole 30 mg "on-demand", 2--lansoprazole 15 mg daily, 3--lansoprazole 30 mg in four-week courses during a relapse. The intensity of symptoms was assessed with the Visual Analogue Scale (VAS) at the baseline, as well after 4 weeks, 3, 6 and 12 months of therapy. The general satisfaction of treatment was evaluated with the Verbal Rating Scale (VRS) at the same time. RESULTS: At the baseline, the mean intensity of symptoms assessed by VAS was 2.8 +/- 1.0 points and fell to 0.4 +/- 0.5 points after a 4-week therapy. In Group 1, after 3, 6 and 12 months, it was 0.85 +/- 0.6, 1.0 +/- 0.8 and 1.0 +/- 0.8, in Group 2: 0.65 +/- 0.7, 0.65 +/- 0.7, 0.5 +/- 0.3, and in Group 3: 1.1 +/- 0.6, 1.55 +/- 0.7, 1.65 +/- 0.8 points, respectively. No significant differences were observed between Groups 1 and 2. Intermittent therapy (Group 3) showed a significantly lower efficacy in comparison to other groups (p < 0.05). "On-demand" therapy was 30% cheaper whereas intermittent therapy was 55% cheaper than the most expensive daily treatment. However, general satisfaction of treatment assessed by VRS was non-significantly different between any of the groups. CONCLUSIONS: In patients with NERD and mild symptoms, both on-demand and daily treatment models of maintenance therapy showed a similar high efficacy, whereas intermittent therapy was significantly less effective. However, general satisfaction of each treatment options was high and non-significantly different between the groups. Due to a pilot character of this study further investigation based on a larger number of patients is necessary to confirm the clinical value of cheaper models of maintenance therapy which could be then recommended as more cost-effective.

[Assessment of fat tissue distribution impact on selected prothrombin and fibrinolytic factors in pre- and postmenopausal women]. / Ocena wplywu typu rozmieszczenia tkanki tluszczowej na wybrane parametry ukladu krzepniecia i fibrynolizy u kobiet w okresie pre- i pomenopauzalnym.

OBJECTIVES: Objective was to examine the relationship of obesity, body fat distribution fasting plasma insulin concentrations and triglycerides of pro-thrombotic and fibrinolitics factors in pre and postmenopausal women. MATERIAL AND METHODS: We assessed 24 (13 nonobese and 11 obese) postmenopausal and 44 (15 obese and 29 non obese) premenopausal women. Plasma concentration of PAI-1 ag,PAI-1 activity, fibrinogen, tPA-1 akt, tPA ag, von Willebrand factor, fasting plasma insulin, and the lipid pattern (cholesterol, TG, HDL, LDL) was measured. The body fat distribution was assessed by waist-to-hip circumference measuring. RESULTS: Postmenopausal subjects had higher PAI-1 act. and PAI-1 ag (p < 0.05 and 0.001 respectively), vWf and lower ATIII. There was direct correlation between PAI-1 act., Fibrinogen and BMI in both groups of patients together and in premenopausal group PAI-1 act correlated directly and tPA ag/act. indirectly with plasma insulin concentrations. CONCLUSIONS: Plasma concentrations of the pro-thrombotic factors are increased in obese and postmenopausal women and correlate directly with BMI and indirectly with plasma insulin concentrations. Plasma concentrations of anti thrombotic factors indirectly correlated with WHR and with plasma insulin concentrations.

[Comparison of platelet activation and procoagulant activity of blood cells in healthy pregnant women and EPH-gestosis patients]. / Porównanie wybranych parametrów koagulologicznych oraz stanu pobudzenia krwinek plytkowych u ciezarnych kobiet z ciaza fizjologiczna i powiklana gestoza EPH.

OBJECTIVES: EPH-gestosis is one of the most frequent complications of pregnancy, labour and puerperium. Despite its unknown ethiology, many authors suggest a vital role played by platelets as an ethiopathogenic factor. The aim of this study was to observe the level of platelets activation in EPH-gestosis subjects. STUDY DESIGN: Platelets activation level has been observed in 16 EPH-gestosis third semester pregnant women and 14 normotensive third semester pregnant controls. Platelets double-labeled with monoclonal antibodies and a flow cytometer have been used in assessment of platelet activation level. Anti-P-selectin (GMP 140- Granule Membrane Protein) has been used as a marker of the platelet released reaction. Fibrinogen, D-dimers, antithrombin and thrombin-antithrombin complexes levels have been analyzed. RESULTS: An increased platelet activation (p < 0.005) as well as the increased level of thrombin-antithrombin (p < 0.005) in pregnant EPH-gestosis women comparing to control group, has been observed in the study. CONCLUSIONS: A state of hypercoaguability and enhanced platelet activation in pregnant EPH-gestosis women have been observed.

[Activation of coagulation cascade in children during an idiopathic nephrotic syndrome relapse]. / Aktywacja ukladu krzepniecia u dzieci w trakcie rzutu idiopatycznego zespolu nerczycowego.

UNLABELLED: The objective of this study was to assess concentrations of selected markers of coagulation in children with relapse of idiopathic nephrotic syndrome during a 6-week therapy. Study groups: 22 subjects (32 relapses)--14 males, 8 females (mean age 7.15 +/- 1.5 y.) with no thrombotic complications were included into the study. All children were clinically steroid-sensitive. METHODS: Coagulation markers (platelet count, thrombin time, APTT, INR, fibrinogen 1 + 2 fragments (F1 + 2), thrombin-antithrombin complexes (TAT), serum levels of D-dimer (DD), fibrin monomers (FM) and antithrombin activity (ATIII)) were measured three times: on admission, after 2 and 6 weeks. The control group consisted of 13 healthy children. RESULTS: Serum concentration of TAT or F1 + 2 did not differ between 3 stages (p > 0.05). However, values at 0 and 2 weeks were significantly higher than in control group (p < 0.05). We found no correlation between TAT or F1 + 2 and FBG, ALB, TCH, TG levels. [table: see text] CONCLUSIONS: The coagulation cascade in relapse of NS was activated during first 6 weeks of therapy whereas metabolic disturbances (low ALB, high FGB, TCH, TG, high platelets) normalized. It is speculative whether it was caused by active immunological process but definitely it resulted in "prothrombotic state" in INS patients.

[The influence of hormone replacement therapy containing transdermal 17-beta estradiol and oral medroxyprogesterone acetate on coagulation and fibrinolysis]. / Wplyw hormonalnej terapii zastepczej pod postacia przezskórnego 17 beta-estradiolu wraz ze stosowanym doustnie octanem medroksyprogesteronu na uklad krzepniecia i fibrynolizy.

OBJECTIVE: The aim of the study was to evaluate some coagulative and fibrinolytic changes in women taking hormone replacement therapy (HRT). MATERIALS AND METHODS: In 29 women aged 45-64 years with osteoporosis and climacteric symptoms several fibrinolytic and coagulative parameters were measured. These measurements were performed three times in each women--before and after three and six months of HRT containing transdermal 17 beta-estradiol (50 mg per day) and oral medroxyprogesterone acetate (2.5 mg per day). RESULTS: PAI-1 (antigen) and factor VII (activity) were decreased significantly during the trial. No other significant modifications in the examined parameters (fibrinogen, antithrombin III, protein C, protein S, thrombin-antithormbin III complexes, t-PA and D-dimers) were detected. CONCLUSIONS: The hormone replacement therapy can reduce the risk of coronary heart disease thanks to decreased levels of PAI-1 and factor VII. No other changes in coagulation and fibrinolysis were observed during the treatment.

[The influence of ursodeoxycholic acid on some biochemical, immunologic and histopathologic parameters in patients with primary biliary cirrhosis]. / Wplyw kwasu ursodezoksycholowego na niektóre parametry biochemiczne, immunologiczne oraz obraz histopatologiczny u chorych z pierwotna zólciowa marskoscia watroby.

UNLABELLED: Primary biliary cirrhosis (PBC) is a chronic, inflammatory disease, which affects the small and medium size bile ducts and is characterized by chronic cholestasis. Ursodeoxycholic acid (UDCA), that had earlier been used in treatment of cholesterol cholelithiasis, was introduced to pharmacotherapy of PBC 10 years ago. Our study was carried out in 30 patients, who were suffering from PBC and were treated at Department of Gastroenterology, Collegium Medicum, Jagiellonian University in Cracow. Beside the routine biochemical and enzymatic tests all patients had the level of immunoglobulin checked and selected ones acute phase protein. The percutaneous liver biopsy was carried out in each case; the morphological changes were classified according to Ludwig scale. All above tests were carried out before implementing UDCA as well as after one year from the beginning of the treatment. The group of patients is still closely monitored. CONCLUSIONS: 1. By using the UDCA in treatment of PBC biochemical parameters of cholestasis improved, also in some cases the inflammatory reaction decreased; 2. UDCA used in monotherapy had no influence on the process of fibrosis.