Tomasz Mach

Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), arginine, and 8‐iso‐prostaglandin F2α (8‐iso‐PGF2α) level in patients with inflammatory bowel diseases

Background: Intestinal microvessels of patients with inflammatory bowel disease (IBD) show microvascular endothelial dysfunction. It may contribute to reduced perfusion, poor ulcer healing, and sustained chronic inflammation. The aim of the study was to assess endothelial dysfunction and oxidative stress markers in patients with IBD. Methods: Serum levels of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), arginine, and 8‐iso‐prostaglandin F2&agr; (8‐iso‐PGF2&agr;) were measured in 31 consecutive patients with ulcerative colitis (UC) and 32 with Crohns disease (CD). Apparently healthy subjects served as age‐ and sex‐matched controls. Associations between these markers and the disease activity and laboratory variables were evaluated. Results: ADMA, SDMA, and 8‐iso‐PGF2&agr; levels were increased in the IBD group as compared to the control group and higher in patients with CD than UC (P < 0.05 for all comparisons). Arginine levels were similar in all the groups. In the CD and UC groups ADMA and SDMA showed positive correlation with 8‐iso‐PGF2&agr; (r from 0.47–0.67; P < 0.01 for all comparisons). ADMA and SDMA correlated positively with the CD activity (r = 0.4, P = 0.025; r = 0.4, P = 0.024, respectively) and the 8‐iso‐PGF2&agr; level correlated positively with the UC activity (r = 0.4, P = 0.026). Conclusions: This is the first study to show that in patients with IBD there is enhanced ADMA generation that might be associated with oxidative stress, and these effects are more pronounced in the CD group. (Inflamm Bowel Dis 2010;)

Can exercise affect the course of inflammatory bowel disease? Experimental and clinical evidence.

The inflammatory bowel disease (IBD) consisting of Crohns disease (CD) and ulcerative colitis (UC) are defined as idiopathic, chronic and relapsing intestinal disorders occurring in genetically predisposed individuals exposed to environmental risk factors such as diet and microbiome changes. Since conventional drug therapy is expensive and not fully efficient, there is a need for alternative remedies that can improve the outcome in patients suffering from IBD. Whether exercise, which has been proposed as adjunct therapy in IBD, can be beneficial in patients with IBD remains an intriguing question. In this review, we provide an overview of the effects of exercise on human IBD and experimental colitis in animal models that mimic human disease, although the information on exercise in human IBD are sparse and poorly understood. Moderate exercise can exert a beneficial ameliorating effect on IBD and improve the healing of experimental animal colitis due to the activity of protective myokines such as irisin released from working skeletal muscles. CD patients with higher levels of exercise were significantly less likely to develop active disease at six months. Moreover, voluntary exercise has been shown to exert a positive effect on IBD patients mood, weight maintenance and osteoporosis. On the other hand, depending on its intensity and duration, exercise can evoke transient mild systemic inflammation and enhances pro-inflammatory cytokine release, thereby exacerbating the gastrointestinal symptoms. We discuss recent advances in the mechanism of voluntary and strenuous exercise affecting the outcome of IBD in patients and experimental animal models.

Possible role of Escherichia coli in propagation and perpetuation of chronic inflammation in ulcerative colitis

BackgroundThis study investigated a possible role of Escherichia coli in propagation and perpetuation of the chronic inflammation in ulcerative colitis (UC). The lesions of UC are located superficially on the rectal and/or colonic mucosa. It is suggested that the commensal bacteria of the digestive tract may play a role in the pathogenesis of UC. Several studies have demonstrated proliferation of E. coli in the gut of UC patients. An increase in the number of E. coli in the inflamed tissue is most probably related to the abundance of iron ions produced by the bacteria.MethodsColon mucosal biopsies were collected from 30 patients with acute-phase UC, both from tissues with inflammatory changes (n = 30) and unchanged tissue with no inflammatory changes (n = 30) from the same patient. Biopsies were also taken from 16 patients with irritable bowel syndrome diarrhea who comprised the control group. Quantitative and qualitative analysis of the biopsy specimens was performed using culture methods and real-time polymerase chain reaction (PCR). Genotyping of the E. coli isolates was done using pulsed-field gel electrophoresis. Multiplex PCR was used to compare the E. coli strains for the presence of genes responsible for synthesis of iron acquisition proteins: iroN, iutA, iha, ireA, chuA, and hlyA.ResultsWe demonstrated that there was a significant increase in the number of E. coli at the sites of inflammation in patients with UC compared to the control group (P = 0.031). Comparative analysis of the restriction patterns of E. coli isolated from inflammatory and unchanged tissues showed that the local inflammatory changes did not promote specific E. coli strains. There was a significant difference in the frequency of the iroN gene in E. coli isolated from patients with UC as compared to the control group.ConclusionsThe increase in the numbers of E. coli in the inflammatory tissues is related to the presence of chuA and iutA genes, which facilitate iron acquisition during chronic intestinal inflammatory processes.

Met-enkephalins in patients with inflammatory bowel diseases

PURPOSEnOpioid 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).nnnMATERIAL AND METHODSnIn serum and colon mucosal biopsy specimens, free met-enkephalin levels were determined in 43 patients with ulcerative colitis (UC) and 38 individuals with Crohns 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.nnnRESULTSnSerum 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.nnnCONCLUSIONSnThe 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.

Reduced plasma fibrin clot permeability and susceptibility to lysis in patients with inflammatory bowel disease: a novel prothrombotic mechanism.

Background:Inflammatory bowel disease (IBD) is associated with an increased risk of thromboembolism. Its mechanism is still unclear. Altered fibrin clot properties have been reported in patients with thromboembolism and those with chronic inflammatory states. We investigated whether fibrin characteristics are abnormal in IBD. Methods:Ex vivo plasma fibrin clot permeability (Ks), compaction, turbidity, and efficiency of fibrinolysis were assessed in 85 consecutive patients with IBD, including 47 with ulcerative colitis (UC) and 38 with Crohns disease (CD), all with no history of thromboembolism. Forty-eight patients matched for age and sex served as controls. Results:Compared with controls, patients with UC and CD had 29.5% and 35.7% lower Ks associated with 13.8% and 23.1% lower compaction, respectively (all P < 0.001). Patients with UC and CD had higher maximum clot absorbance (+8.9%, P = 0.008, and +15.2%, P < 0.0001, respectively), higher maximum D-dimer released from clots (D-Dmax, +27.0%, P = 0.01, and +28.7%, P < 0.0001, respectively), and prolonged clot lysis time (+19.0%, P < 0.0001, and +25.5%, P < 0.0001, respectively). Lag phase was similar in both group of patients. D-Dmax was the only parameter that differed between patients in the UC and CD groups, being higher in CD (P = 0.04). The multiple linear regression model showed that in patients with UC, but not with CD, Ks, compaction, lysis time, and D-Dmax were all independently associated with disease activity. In patients with CD, Ks and lysis time were independently predicted by fibrinogen and C-reactive protein. Conclusions:Both UC and CD are characterized by formation of dense fibrin networks relatively resistant to lysis. Prothrombotic clot phenotype might represent a novel mechanism increasing thrombotic risk in IBD.

Autonomic nervous system activity in constipation-predominant irritable bowel syndrome patients

Summary Background The main mechanism underlying irritable bowel syndrome is currently believed to be a dysfunction of the brain-gut axis. Autonomic nervous system dysfunction can contribute to development of irritable bowel syndrome symptoms by disturbing visceral sensations. Material/Methods Thirty patients with a diagnosis of constipation-predominant irritable bowel syndrome and 30 healthy volunteers were included in the study. Resting and functional autonomic nervous system tests and percutaneous electrogastrography were performed. Plasma adrenalin, noradrenalin, insulin, ghrelin and cholecystokinin activity was analyzed. Results Increased sympathetic activation with disturbed parasympathetic function was demonstrated. Patients had substantially higher plasma catecholamine concentration, which confirms sympathetic overbalance. Hyperinsulinemia may explain sympathetic predominance followed by gastric and intestinal motility deceleration. Abnormal, reduced ghrelin and cholecystokinin titre may disturb brain-gut axis functioning and may be responsible for gastric motility deceleration. In electrogastrography, distinctly lower values of fasting normogastria percentage and dominant power were observed. Patients had substantially lower slow wave coupling percentage both in fasting and postprandial periods, which negatively correlated with plasma catecholamines level. Gastric myoelectrical activity disturbances may result from lack of sympatho-parasympathetic equilibrium. Conclusions Central sympathetic influence within the brain-gut axis is most probably responsible for myoelectrical activity disturbances in irritable bowel syndrome patients.

The Role of Intestinal Alkaline Phosphatase in Inflammatory Disorders of Gastrointestinal Tract

Over the past few years, the role of intestinal alkaline phosphatase (IAP) as a crucial mucosal defence factor essential for maintaining gut homeostasis has been established. IAP is an important apical brush border enzyme expressed throughout the gastrointestinal tract and secreted both into the intestinal lumen and into the bloodstream. IAP exerts its effects through dephosphorylation of proinflammatory molecules including lipopolysaccharide (LPS), flagellin, and adenosine triphosphate (ATP) released from cells during stressful events. Diminished activity of IAP could increase the risk of disease through changes in the microbiome, intestinal inflammation, and intestinal permeability. Exogenous IAP exerts a protective effect against intestinal and systemic inflammation in a variety of diseases and represents a potential therapeutic agent in diseases driven by gut barrier dysfunction such as IBD. The intestinal protective mechanisms are impaired in IBD patients due to lower synthesis and activity of endogenous IAP, but the pathomechanism of this enzyme deficiency remains unclear. IAP has been safely administered to humans and the human recombinant form of IAP has been developed. This review was designed to provide an update in recent research on the involvement of IAP in intestinal inflammatory processes with focus on IBD in experimental animal models and human patients.

Cognitive functions in patients with liver cirrhosis: A tendency to commit more memory errors

Background Minimal hepatic encephalopathy (MHE) is the mildest form of hepatic encephalopathy (HE). For diagnostic purposes, 2 alternative batteries of psychometric screening tests are recommended. They differ from each other in terms of the cognitive domains assessed. The research was designed to provide a profile of cognitive functioning in patients with liver cirrhosis, using an assessment that covers a wider range of cognitive functions than the usual screening battery. Material/Methods We examined 138 persons, including 88 with liver cirrhosis and 50 healthy volunteers. The Mini Mental State Examination (MMSE) was used for screening and excluding advanced cognitive impairment. Then, to assess cognitive functions in more detail, the following tests were used: Auditory Verbal Learning Test (AVLT), Letter and Semantic Fluency Tests (LF and SF), Trail Making Test (TMT A&B), Digit Symbol Test (DST), Block Design Test (BDT), and Mental Rotation Test (MRT). The MRT task has not been used in MHE diagnosis so far. Finally, 57 patients and 48 controls took part in the entire study. Results Patients with liver cirrhosis commit significantly more errors of intrusions in the AVLT during the delayed free recall trial. Results significantly deviating from the norm in at least 2 tests were found only in 7 cirrhosis patients. Conclusions The results do not provide any specific profile of cognitive disturbances in MHE, but suggest that cirrhosis patients have a tendency to commit more memory errors, probably due to subtle impairments of executive function.

The case of a diffuse large B-cell lymphoma (DLBCL) in a course of HIV

Summary Background Lymphomas develop in approximately 6% of HIV-positive patients, who are estimated to have a 100-200-fold higher risk of lymphoma and as much as a 1000-fold higher risk of primary cerebral lymphoma. Case Report Patient T.R., age 33, HIV positive – diagnosis 3 years before, CD4 = 120/ul, he didnt agree to continue HAART. Two months before present hospitalization developed an enlarged lymph node in the left axilla, substantially increased in diameter reaching 12 cm, and an infiltration of the chest skin. The enlarged lymph node was sampled, and in a microscopic evaluation it was diagnosed as diffuse large B-cell lymphoma (DLBCL). After establishing the diagnosis, the patient received antiretroviral therapy (tenofovir, lamivudine, lopinavir, ritonavir) and courses of chemotherapy according to the CHOP regimen (cyclophosphamide, vincristine, doxorubicin, prednisone) combined with rituximab. The treatment resulted in a marked local tumor regression in the chest and left axilla. During the lymphoma therapy numerous complications were observed. Psychologically, the patient was very optimistic until the last chemotherapy cycle. He died after the fifth cycle. Conclusion The decision to start chemotherapy and HAART should be taken individually for every patient. Unfortunately, despite the recent advances in therapy, the prognosis in HIV-positive patients with lymphomas remain poor.

Zapalenie osierdzia i mięśnia sercowego — niecodzienna pozajelitowa manifestacja wrzodziejącego zapalenia jelita grubego

Ulcerative colitis (UC) is an example of inflammatory bowel disease that can be manifested by extraintestinal complications including cardiac disorders. The most commonly reported — pericarditis — occurs in 0.23% of all UC patients. The knowledge about the etiology of pericarditis is important to implement accurate therapy. However, the diagnosis is not always clear and can be connected with diagnostic and therapeutic challenges. In this case, we present a myopericarditis in the course of UC exacerbation.