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.

Lipid peroxidation, reactive oxygen species and antioxidative factors in the pathogenesis of gastric mucosal lesions and mechanism of protection against oxidative stress - induced gastric injury.

The gastric mucosa plays an important role in the physiological function of the stomach. This mucosa acts as gastric barrier, which protects deeper located cells against the detrimental action of the gastric secretory components, such as acid and pepsin. Integrity of the gastric mucosa depends upon a variety of factors, such as maintenance of microcirculation, mucus-alkaline secretion and activity of the antioxidizing factors. The pathogenesis of gastric mucosal damage includes reactive oxygen species (ROS), because of their high chemical reactivity, due to the presence of uncoupled electron within their molecules. Therefore they cause tissue damage, mainly due to enhanced lipid peroxidation. Lipid peroxides are metabolized to malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). The local increase of MDA and 4-HNE concentration indicates ROS-dependent tissue damage. Superoxide dismutase (SOD) is the main enzyme, which neutralizes ROS into less noxious hydrogen peroxide. A decrease of SOD activity is an indicator of impairment of the protective mechanisms and significantly contributes to cell damage. Hydrogen peroxide is further metabolized to water in the presence of reduced glutathione (GSH). GSH can also work synergetically with SOD to neutralize ROS. The reactions between GSH and ROS yields glutathione free radical (GS(•)), which further reacts with GSH leading to free radical of glutathione disulphide (GSSG(•)). This free radical of GSSG can then donate an electron to the oxygen molecule, producing O2 (•-) Subsequently, O2 (•-) is eliminated by SOD. Adecrease of the GSH level has detrimental consequences for antioxidative defense cellular properties. Gastric mucosa, exposed to stress conditions, exhibits an enhancement of lipid peroxidation (increase of MDA and 4-HNE), as well as a decrease of SOD activity and GSH concentration. This chain reaction of ROS formation triggered by stress, appears to be an essential mechanism for understanding the pathogenesis of stress - induced functional disturbances in the gastric mucosa leading to ulcerogenesis.

Disturbances of autonomic nervous system activity and diminished response to stress in patients with celiac disease.

Celiac disease (CED) is immune-mediated enteropathy caused by gluten intolerance affecting genetically predisposed individuals. CED may exert a number of various symptoms, including extra intestinal manifestations. Neurological symptoms can be the first sign of gluten intolerance. However, affected autonomic nervous system (ANS) activity may be linked to other symptoms. We evaluated the frequency of ANS impairment and resting ANS response to several stimuli in CED patients without neurological manifestations. Twenty five neurologically asymptomatic patients with CED were studied. The medical history was taken and ANS activity was determined. ANS tests included heart rate variability (HRV) at rest and after stimulation (sympathetic - stress, and parasympathetic - deep breathing). The results were compared with those of the control group comprising of 30 healthy asymptomatic volunteers. Both the resting HRV parameters and the HRV indices recorded after deep breathing (parasympathetic stimulation) were significantly lower in patients with CED than in the controls (P<0.05). Also the stress-induced increase in normalized low frequency parameter (LFnu) was significantly lower in the CED group than in the control group (P<0.05). Overall, about 20% of CED patients presented with parasympathetic dominancy but 36% with sympathetic dominancy, and 44% of patients did not show changes in sympathetic-vagal balance of the autonomic nervous system. We conclude that sympathetic-parasympathetic imbalance, in favour of more often sympathetic than parasympathetic overactivity occurs among neurologically asymptomatic CED patients. The ANS impairment observed in the course of CED may result from prolonged intestinal inflammation. Therefore, routine ANS testing might be considered in patients presenting with this condition.

[Knee pain: choosing the right imaging]. / Gonalgies: quelle imagerie?

Gonalgia is a frequent reason for consultation of a primary care physician. The road leading to diagnosis is mainly clinical. A detailed medical history and physical examination are capital for establishing diagnostic hypotheses and choosing the most appropriate imaging test. Initially, a simple X-ray of the knee joint is the most common exam, even though it is not always needed, especially after a minor trauma. MRI and CT-scan allow a more detailed examination of the structures; however, they should only be ordered to answer a specific question. Most of the time, echography is reserved to extra-articular pathologies and for guiding an articular tap.

Expression and release of leptin and proinflammatory cytokines in patients with ulcerative colitis and infectious diarrhea.

Leptin plays not only an important role in regulation of food intake, but also in the mechanism of inflammation. The universal presence of leptin in the cells of immune system and its secretion by these cells caused increasing interest in the role of this hormone in ulcerative colitis (UC). We determined the role of leptin in 80 patients, aged from 18 to 69 years, including 50 patients with active UC and 30 patients with infectious diarrhea. The tests were performed within 48 hours of the first symptoms, in the period of remission of UC and 8 weeks after resolution of infectious diarrhea. Endoscopy was performed in each patient, and the biopsy samples were taken for the assessments of expression of mRNA for leptin, IL-1ß, IL-6 and TNF-α by RT-PCR and Western blot. Blood tests included concentrations of leptin, IL-1ß, IL-6 and TNF-α. In addition, the plasma levels of leptin, IL-1ß, IL-6 and TNF-α were assessed by ELISA. Serum concentrations of leptin was significantly increased in patients with exacerbation of UC over that in patients with UC in remission. The serum leptin concentration was significantly higher in patients with infectious diarrhea, than the patients that recovered from infectious diarrhea. The leptin protein was overexpressed in the biopsy samples of the mucosa of large intestine compared to those with exacerbation of UC, and in patients after successful recovery from infectious diarrhea. The leptin mRNA was overexpressed in patients with infectious diarrhea compared with that in the group of patients after successful recovery from this condition. Serum concentrations of leptin failed to correlate with severity of exacerbation of UC and with extent of intestinal inflammatory lesions in patients with UC. However, the correlation was observed between serum concentrations of leptin in patients with exacerbation of UC and serum concentrations of proinflammatory cytokines IL-1ß and TNF-α. We conclude that 1) the increased leptin in exacerbated UC is related to the increased serum proinflammatory cytokines IL-1ß, TNF-α and IL-6 levels; 2) In patients with infectious diarrhea, the concentrations of leptin in intestinal mucosa correlates with serum concentrations of cytokines IL-1ß, IL-6 and TNF-α and with an increased expression of leptin mRNA in intestinal mucosa but not with alterations in serum levels of this hormone; 3) leptin may serve as useful predictive marker of inflammation in inflammatory bowel disease (IBD).

Electrophysiological correlates of attentional processes in patients with liver cirrhosis without minimal or clinically-overt hepatic encephalopathy.

Liver cirrhosis is often accompanied by a spectrum of cognitive deficits, labelled hepatic encephalopathy (HE). The precise specification of cognitive impairment associated with HE has not been yet elucidated. The aim of this study was an attempt to examine cortical function in cirrhotic patients using EEG event-related potentials during a demanding task involving selective attention. We compared group of 30 patients with liver cirrhosis without minimal or overt HE with education-, age- and sex-matched 29 non-cirrhotic controls. Both groups performed an attentional blink (AB) task, which requires detecting and identifying two target characters in a longer series of rapidly and sequentially presented characters. EEG signals from 32 electrodes were measured and then analyzed in the paradigm of event-related potentials (ERP). Though the groups did not differ in the detection rate of the target stimuli, ERP waveforms revealed two group differences of component amplitudes. The first difference was related to the waveform amplitude within the 200-400 ms after first target in the right frontal region (frontocentral N2 component). Moreover, in patient group this amplitude positively correlated with the blood plasma level of alkaline phosphatase and gamma-glutamyl transpeptidase. The second amplitude difference was observed in the midline parieto-occipital regions within the 400-600 ms after the first target (P3b component). The AB task and ERP analysis allowed to find differences in cortical functioning in cirrhotic patients even without overt cognitive deficits. Our finding demonstrates that liver dysfunction can influence cortical processing associated with detecting and categorizing stimulus change.

Endovascular treatment of infected aortic aneurysms.

OBJECTIVE: To report on the short- and long-term outcomes of patients with primary infected aortic aneurysm (IAA) treated by stent graft (SG) in two centers. MATERIAL AND METHOD: Over a period of 15 years, 32 patients with IAA underwent endovascular treatment. None had undergone previous aortic surgery. The causal relationship was gastrointestinal infection in 9 patients (28%), endovascular diagnostic/therapeutic procedures/resuscitation in 6 (19%), wound infection after previous surgeries in 5 (16%), urinary infection in 4 (13%), urology or gastroenterology procedures in 3 (9%), pancreatitis in 2 (6%), endocarditis in 1 (3%) and phlebitis in 1 (3%) patient. We implanted 11 bifurcated, 10 tubular thoracic, 4 aorto-uni-iliac, 4 tubular abdominal and 1 iliac SG. Two other surgeries were hybrid procedures. RESULTS: The etiological agent was identified in 28 (88%) patients. Twenty-six (81%) patients survived the 30-day postoperative period. Sixteen (50%) survived to 1-year follow-up and 13 (40.6%) survived to 3-year follow-up. Three patients have survived for less than 1 year and a further 3 for less than 3 years, so far. Among patients with aneurysms situated in central parts of the thoracic and infrarenal aorta there was a better death/survival ratio than among patients with a proximal or distal aneurysm location. CONCLUSION: The implantation of a SG may be an alternative to open surgery in selected groups of patients with primary IAA. Aneurysms of the central part of the thoracic or abdominal aorta have a more favorable prognosis with endovascular treatment.

Cognitive evoked response potentials in patients with liver cirrhosis without diagnosis of minimal or overt hepatic encephalopathy. A pilot study.

Liver cirrhosis is often accompanied by cognitive deficits called minimal hepatic encephalopathy (MHE) when it is observed to a moderate extent. In the present study, brain activity and cognitive functioning were examined in patients with liver cirrhosis without MHE or overt clinical hepatic encephalopathy. A battery of neuropsychological tests and event related potentials (ERPs) were used. Moreover, an additional n-back task was administered with two difficulty levels (1- and 2-back). This task was designed to engage cognitive processes of storage and manipulation of information in working memory. The participants have to decide whether the letter shown was the same as a target (congruence condition). No significant differences were found in the performance of either the neuropsychological tests or the n-back task. However, the expected effects of decreased performance as well as a decrease in P3 amplitude with difficulty level were identified. The interaction of group x congruence condition was also observed in the P2 component time window. These results may indicate group differences manifesting in early stages of information processing in working memory. It confirms that the patients whose neuropsychological performance is within the normal range can still reveal subtle changes in CNS functioning visible in ERP research. The study confirms the usability of the ERP method in diagnosis of neurocognitive functions in patients with liver cirrhosis, which seems to be more sensitive than neuropsychological tests.

The diagnostic value of cytokine and nitric oxide concentrations in cerebrospinal fluid for the differential diagnosis of meningitis.

PURPOSE: In several cases of meningitis routinely used diagnostic procedures are unable to identify the cause of this disease. The objective of the present study was to determine whether proinflammatory cytokine (tumour necrosis factor (TNF-α), interleukin-1ß (IL-1ß), interleukin-8 (IL-8)) and nitric oxide (NO) concentrations in the CSF are useful markers for the differential diagnosis of meningitis. MATERIAL AND METHODS: Sixty-seven patients (42 patients with bacterial meningitis and 25 patients with viral meningitis) were included in the present study. In the investigated group, the TNF-α, IL-1ß and IL-8 concentrations in the CSF samples collected on the day of admission were assessed. Furthermore, the NO concentrations were assessed in 23 patients. RESULTS: The results revealed that the measurement of proinflammatory cytokines in CSF can aid in a differential diagnosis. In particular, a high concentration of TNF-α may be a sensitive and specific marker of a bacterial aetiology of the neuroinfection. In the present study, TNF-α concentrations greater than 75.8 pg/ml differentiated between bacterial and viral meningitis with 100% sensitivity and specificity. The NO concentration in the CSF was also significantly greater in patients with bacterial meningitis than in those with viral meningitis. CONCLUSIONS: The assessment of TNF-α, IL-1ß and IL-8 concentrations in the CSF is useful in the differential diagnosis of neuroinfection. Because many factors may influence NO production in the central nervous system (CNS), it is not clear whether NO values can be used for the differential diagnosis of meningitis, and further studies are required.

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.

[Changes in the true and false visceral segment lumen sizes following endovascular treatment of type B aortic dissections]. / Zmeny velikosti pravého a falesného lumen ve viscerálním segmentu po endovaskulární lécbe disekcí aorty typu B.

INTRODUCTION: The aim of the study was to assess technical success rates of endovascular procedures in acute and chronic type B aortic dissections and changes in the right (PL) and false (FL) lumen diameters in the visceral segment region during short-term and long-term follow up study periods. METHODS: From 2004 to 2009, the authors performed a prospective study, which included a total of 33 patients with acute and subacute (n = 16; 48.5%) or chronic (n = 17; 51.5%) type B dissections of the descending aorta, with dissections spreading as far as the visceral or infrarenal regions. The patients underwent successful implantations of stent grafts (SG) into the descending aorta. The study group included 7 female and 26 male subjects, at the time of the procedure, their mean age was 59 years, (34-70, the median of 56 y.o.a.). The mean follow up time was 39.3 months (8-68, the median of 41 months). During the study period, one of the patients exited due to another internal disorder, three subjects were converted to open replacements for progressing dilatation of the total diameter in the visceral or subrenal region. The true (PL) and false (FL) lumen diameters were measured at four levels: above the origin of truncus coeliacus (L 1), between the origin of truncus coeliacus and the origin of a. mesenterica superior (L 2), between the origin of a. mesenterica superior and the origin of aa. renales (L 3) and just distal to the origin of aa. renales (L 4). The measurements were performed 1 and 6 months after SG implantations and at the end of the study period. RESULTS: The primary entry was successfully sealed in all the study subjects. Significant widening of the true lumen in the region sealed by the stentgraft was recorded in all the subjects, however, the false lumen did not completely disappear in 3 (9%) patients. The false lumen was completely filled with thrombus down to the celiac trunk level (L 1) within one month in 7 (21.2%) patients, within 6 months in 14 (42.4%) subjects and by the end of the study period in 19 (58.6%) patients. The true lumen continued to enlarge at all the measured levels. The most significant enlargement was recorded at L 1 during the first postoperative month (the mean change of 5.9 mm). Furthermore, narrowing of the originally patent false lumen was observed as well, with the most significant change at L1 level during the first postoperative month (the mean change of 6.5 mm). At six months and during the whole follow up study period, further increases in the right lumen diameter and in the total aortic diameter were recorded at all the measured levels. At the same time, the false lumen diameters at all the measured levels continued to narrow, if patent at all. CONCLUSION: False lumen thrombosis along the extent of SG was recorded in 30 (91%) patients, SG filled the lumen completely and the false lumen disappeared. The true lumen expanded at all the measured visceral segment levels. The change was most significant during the first postimplantation month, and the true lumen expansions and the false lumen narrowing proceeded over the whole follow up study period, however, the progression was slower. The visceral segment true and false lumen changes will be monitored further.

[Prevention of type II endoleak using postoperative coiling of the abdominal aortic aneurysm sac during stent graft implantation]. / Prevence endoleaku II. typu pomocí peroperacního coilingu vaku aneuryzmatu abdominální aorty behem implantace stentgraftu.

AIM: A prospective randomized study assessing the success rates of type II endoleak (EL) prevention, using postoperative coiling of the abdominal aortic aneurysm (AAA) sac during stent graft (SG) implantation. MATERIAL AND METHODS: From January 2008 to July 2009, 86 patients were operated for AAA using endovascular methods with bifurcation SG. The subjects were prospectively randomized into two subgroups. Group A subjects (42 subjects; 48.8%) had various numbers of coils introduced into the sac, close to the SG body. Group B (44 subjects; 51.2%) included patients without coils. Preoperative CT angiograhy (CT AG) was used to assess patency and the number of lumbal arteries (AL), a.mesenterica inferior (AMI), a. sacralis mediana (ASM) and aa. renales accessoriae (ARA), the AAA sac and the lumen size. At the end of the studied period, existence of type II EL and the AAA sac size was assessed using sonography and /or CT AG. RESULTS: Prior to the procedure, there were only minor differences in the number of source type II EL arteries (AL 3.8 vs. 3.5; AMI 0.78 vs. 0.55; ASM 0.26 vs. 0.3; ARA 0.095 vs. 0.05), preoperative AAA sac size (68.6 vs. 67.0 mm) and the lumen size (47.6 vs. 40.0 mm), the AAA sac size at the end of the studied period (63.9 vs. 62.1 mm) and its mean size change (-4.7 vs. -4.9 mm), between the Group A and B, respectively . Postoperatively, the type II EL was detected in 6 subjects in Group A (14.3%), and in 9 subjects in Group B (20.5%). At the study endpoint, the type II EL was identified in 4 subjects in Group A (9.5%), in 8 subjects in Group B (18.2%). CONCLUSION: Peroperative introduction of coils into the AAA sac is one of the options for type II EL prevention. It facilitates successful regression and disappearance of type II EL.

Effect of Candida colonization on human ulcerative colitis and the healing of inflammatory changes of the colon in the experimental model of colitis ulcerosa.

The influence of fungal colonization on the course of ulcerative colitis (UC) has not been thoroughly studied. We determined the activity of the disease using clinical, endoscopic and histological index (IACH) criteria in UC patients with fungal colonization and the healing process of UC induced by an intrarectal administration of trinitrobenzene sulfonic acid (TNBS) in rats infected with Candida, without and with antifungal (fluconazole) or probiotic (lacidofil) treatment. The intensity of the healing of the colonic lesions was assessed by macro- and microscopic criteria as well as functional alterations in colonic blood flow (CBF). Myeloperoxidase (MPO) content and plasma proinflammatory cytokines IL-1beta and TNF-alpha levels were evaluated. Candida more frequently colonized patients with a history of UC within a 5-year period, when compared with those of shorter duration of IBS. Among Candida strains colonizing intestinal mucosa, Candida albicans was identified in 91% of cases. Significant inhibition of the UC activity index as reflected by clinical, endoscopical and histological criteria was observed in the Candida group treated with fluconazole, when compared to that without antifungal treatment. In the animal model, Candida infection significantly delayed the healing of TNBS-induced UC, decreased the CBF and raised the plasma IL-1beta and TNF-alpha levels, with these effects reversed by fluconazole or lacidofil treatment. We conclude that 1) Candida delays healing of UC in both humans and that induced by TNBS in rats, and 2) antifungal therapy and probiotic treatment during Candida infection could be beneficial in the restoration and healing of colonic damage in UC.

[Urgent endovascular management of the thoracic aorta dissection and subsequent lower extremity ischemia]. / Akutní endovaskulární rerení disekce hrudní aorty a následné ischemie dolních koncetin.

SITUATION: Insertion of tubular stentgrafts in the management of acute type B dissection of the thoracic aorta has recently become a popular alternative to open surgeries. The classical surgical procedure in complicated dissections is associated with mortality rates of up to 50% and prolonged intensive care hospitalization. However, endovascular procedures have been associated with significantly lower morbidity and mortality rates. There is insufficient experience with the stentgraft implantation outcome concerning both the septum dissection and the lumini. CASE REVIEW: A tubular stentgraft has been implanted to a forty-nine-year-old patient with acute, type B dissection. Immediate ischemic and neurological complications, requiring reoperation and prolonged intensive care, were recorded postoperatively. The causes and the management are discussed. CONCLUSION: Endovascular management of the type B dissection is a popular, more patient-saving and healthcare professionals-saving procedure, compared to classical open surgery. Pressure changes in the true and false aortic lumen may result in rapid reduction of the organ and limb perfusion flow. These complications should be expected and must be managed urgently. Such surgeries should be performed in clinical centres with appropriate facilities.

Magnetic field anti-inflammatory effects in Crohn's disease depends upon viability and cytokine profile of the immune competent cells.

AIM: We investigated effects of pulsating electromagnetic field (PEMF-50 Hz, 45 +/- 5 mT) on viability and cytokine production by human peripheral blood mononuclear cells (PBMC) from healthy donors and from Crohn's disease patients (CD). METHODS: The study was performed after activation of cells with phytohaemaglutinin (PHA) and lipopolisaccharide (LPS). Exposure of PBMC cultures to PEMF from both CD patients and from healthy donors decreased cell's viability of about 10% and 5% (p>0.05) respectively. PEMF influence was most effective after threefold application. Susceptibility of PBMCs to magnetic field exposure differs among the stimulated (PHA, LPS) and not stimulated (NS) cells. Mitogen activated cells during cell division are most susceptible to induction of the cell death as a result of magnetic interaction, contrary PEMF exposure has minimal effect on non-diving PBMCs from CD patients and from controls. Decreased viability of the Crohn derived cells upon magnetic stimulation was accompanied by altered cytokines profile. Exposed and stimulated PBMCs from Crohn patients decreased IFN-gamma proinflammatory and increased IL-10 anti-inflammatory cytokine production. The electromagnetically induced cell death could be an important step for non-invasive PEMF treatment in chronic inflammatory diseases.

Opportunistic infections and other AIDS-defining illnesses in Poland in 2000-2002.

BACKGROUND: The introduction of highly active antiretroviral therapy (HAART) led to a decreased incidence of the most severe opportunistic infections (OIs) in HIV-infected patients. In Poland, HAART became widely used in 1998. MATERIALS AND METHODS: This study was based on data from medical records data collected in the years 2000-2002 from medical centers for HIV-infected patients in Poland. The aim of the study was to determine the incidence of opportunistic infections (OIs) and other AIDS defining illnesses (ADIs). The chi(2) test was used to determine any significant trends. RESULTS: The incidence of ADIs was 6.8, 6.5 and 4.8/100 persons/year in 2000-2002, respectively. The most common diagnosed OIs were: fungal infections, tuberculosis, recurrent pneumonia, PCP and toxoplasmosis. In patients receiving HAART (HAART+) the incidence of ADIs was significantly lower than in non-ARV-treated as well as in all HIV+ (p < 0.02, p < 0.001, p < 0.001, respectively). A significant decrease in the incidence of ADIs in HAART+ patients between 2000 and 2002 (p < 0.0001) was observed. From 25% to 30% of ADIs among HAART+ patients were diagnosed within the first 3 months of antiretroviral therapy. In HAART+ patients the most common ADIs were fungal infections and tuberculosis. The diagnosis of ADIs resulted in the recognition of HIV status in 8.7-8.9% of patients. CONCLUSIONS: Five years after the introduction of HAART the incidence of ADIs had declined. Fungal infections and tuberculosis were the most common OIs in HIV+ patients in Poland.

Clinical usefulness of probiotics in inflammatory bowel diseases.

Probiotics are live nonpathogenic bacteria or bacterial components that may be helpful in the prevention and treatment of acute diarrhoea in adults and children and have some effects on the course of inflammatory bowel diseases (IBD). Many experimental and clinical studies suggest that intestinal bacterial flora plays an important role in the pathogenesis of IBD, and manipulation of the luminal contents with antibiotics or probiotics represents a potentially effective therapeutic option. The beneficial effect of probiotics was demonstrated mainly in the prevention and treatment of pouchitis and in maintaining remission of mild to moderate ulcerative colitis. Probiotics seems to be less effective in patients with Crohn's disease. Randomized clinical trials are still required to further define the role of probiotics as preventive and therapeutic agents. This review summarizes the current data about probiotics in IBD.

Are probiotics effective in the treatment of fungal colonization of the gastrointestinal tract? Experimental and clinical studies.

UNLABELLED: The influence of fungal colonization and probiotic treatment on the course of gastric ulcer (GU) and ulcerative colitis (UC) was not explored. Our studies included: 1) clinical investigation of 293 patients with dyspeptic and ulcer complaints and 72 patients with lower gastrointestinal (GI) tract: 60 patients with UC, 12 with irritable bowel syndrome (IBS) - the control group. Significant fungal colonization (SFC), over 10(5) CFU/ml was evaluated. Mycological investigation was performed, including qualitative and quantitative examination, according to Muller method, 2) experimental studies in rats included estimation of the influence of inoculation of Candida isolated from human GI tract on the healing process of GU, induced by acetic acid with or without probiotic Lactobacillus acidophilus (10(6) CFU/ml) introduced intragastrically (i.g.). At 0, 4, 15 and 25 day after ulcer induction. Weight, damage area, gastric blood flow (GBF) (H2 clearance), expression of mRNA for cytokines IL-beta, TNF-alpha (ELISA) were evaluated. Mycology: qualitative and quantitative examination was performed. MPO serum activity was measured. Results of clinical studies: 1) SFC was more frequent in patients with GU: 54.2% of cases and patients with over 5 years history of UC: 33.3% cases. 2) SFC delayed GU healing and influenced the maintenance of clinical symptoms in both diseases. Results of animal studies: 3) In Candida inoculated rats, the GBF was significantly lower than in the vehicle controls (saline administered group). Upregulation of TNF-alpha, IL-1 beta was recorded. The GUs were still present till 25 day in all rats inoculated with Candida, in contrast to vehicle group (reduction of ulcer in 92% at day 25). CONCLUSIONS: 1) Fungal colonization delays process of ulcer and inflammation healing of GI tract mucosa. That effect was attenuated by probiotic therapy. 2) Probiotic therapy seems to be effective in treatment of fungal colonization of GI tract. 3) Lactobacillus acidophilus therapy shortens the duration of fungal colonization of mucosa (enhanced Candida clearance is associated with IL-4, INF-gamma response).

Met-enkephalin in the liver as a marker of hepatocellular damage in chronic viral hepatitis type B and C.

PURPOSE: The aim of the study was to assess the liver Met-enkephalin concentration in chronic viral hepatitis type B and C as well as in liver cirrhosis in order to estimate the role of opioid system in pathogenesis of liver disease. MATERIAL AND METHODS: The concentration of Met-enkephalin was examined in liver tissue of 103 consecutive patients with chronic hepatitis type B and C. Control group consisted of uninfected patients. Met-enkephalin concentration was analyzed in relation to the degree of hepatic necroinflammatory activity and the extent of fibrosis estimated by histopathological examination of liver bioptates and compared to such parameters as age, sex and concomitant diseases. RESULTS: Significant differences in Met-enkephalin concentration were found between cases with advanced fibrosis (stage 3 and 4 acc. to Batts and Ludwig classification) and cases with fibrosis classified as stage 2 (p < 0.05). Met-enkephalin concentration was higher in HCV infected patients in comparison to HBV infected patients (p < 0.05) and uninfected controls (0.05 < p < 0.1). There wasn't found any correlation between Met-enkephalin level and necroinflammatory activity in the liver, age, sex and concomitant diseases. CONCLUSIONS: Met-enkephalin concentration measurement in the liver tissue seams to be a useful method for differentiation of stage 2 from stages 3 and 4 of severe liver fibrosis. There is increased concentration of Met-enkephalin in liver tissue in HCV infected patients in comparison to HBV infected or uninfected individuals. The degree of necroinflammatory activity in the liver as well as sex and age of patients with chronic hepatitis do not correlate with changes in opioid system.