Agnieszka Mastalerz-Migas

Serum and urine metabolomic fingerprinting in diagnostics of inflammatory bowel diseases.

AIM To evaluate the utility of serum and urine metabolomic analysis in diagnosing and monitoring of inflammatory bowel diseases (IBD). METHODS Serum and urine samples were collected from 24 patients with ulcerative colitis (UC), 19 patients with the Crohns disease (CD) and 17 healthy controls. The activity of UC was assessed with the Simple Clinical Colitis Activity Index, while the activity of CD was determined using the Harvey-Bradshaw Index. The analysis of serum and urine samples was performed using proton nuclear magnetic resonance (NMR) spectroscopy. All spectra were exported to Matlab for preprocessing which resulted in two data matrixes for serum and urine. Prior to the chemometric analysis, both data sets were unit variance scaled. The differences in metabolite fingerprints were assessed using partial least-squares-discriminant analysis (PLS-DA). Receiver operating characteristic curves and area under curves were used to evaluate the quality and prediction performance of the obtained PLS-DA models. Metabolites responsible for separation in models were tested using STATISTICA 10 with the Mann-Whitney-Wilcoxon test and the Students t test (α = 0.05). RESULTS The comparison between the group of patients with active IBD and the group with IBD in remission provided good PLS-DA models (P value 0.002 for serum and 0.003 for urine). The metabolites that allowed to distinguish these groups were: N-acetylated compounds and phenylalanine (up-regulated in serum), low-density lipoproteins and very low-density lipoproteins (decreased in serum) as well as glycine (increased in urine) and acetoacetate (decreased in urine). The significant differences in metabolomic profiles were also found between the group of patients with active IBD and healthy control subjects providing the PLS-DA models with a very good separation (P value < 0.001 for serum and 0.003 for urine). The metabolites that were found to be the strongest biomarkers included in this case: leucine, isoleucine, 3-hydroxybutyric acid, N-acetylated compounds, acetoacetate, glycine, phenylalanine and lactate (increased in serum), creatine, dimethyl sulfone, histidine, choline and its derivatives (decreased in serum), as well as citrate, hippurate, trigonelline, taurine, succinate and 2-hydroxyisobutyrate (decreased in urine). No clear separation in PLS-DA models was found between CD and UC patients based on the analysis of serum and urine samples, although one metabolite (formate) in univariate statistical analysis was significantly lower in serum of patients with active CD, and two metabolites (alanine and N-acetylated compounds) were significantly higher in serum of patients with CD when comparing jointly patients in the remission and active phase of the diseases. Contrary to the results obtained from the serum samples, the analysis of urine samples allowed to distinguish patients with IBD in remission from healthy control subjects. The metabolites of importance included in this case up-regulated acetoacetate and down-regulated citrate, hippurate, taurine, succinate, glycine, alanine and formate. CONCLUSION NMR-based metabolomic fingerprinting of serum and urine has the potential to be a useful tool in distinguishing patients with active IBD from those in remission.

Immune Response to Influenza Vaccine in Hemodialysis Patients with Chronic Renal Failure

Chronic renal failure and dialysis belong to contraindications to vaccination with live vaccines. The objective of this study was to evaluate the humoral response to influenza vaccination consisting of the formation of antibodies against hemagglutinin and neuraminidase in patients undergoing chronic hemodialysis due to chronic renal failure. The study included 173 patients treated at a dialysis station in the Silesian region in Poland. The patients were assigned to the following groups: Group A-71 hemodialysis patients, mean age 65.4 ± 14.5 years; mean time of dialysis therapy 38.9 ± 31.7 months, vaccinated against influenza; Group B-39 hemodialysis patients, mean age 64 ± 13.5 years; mean time of dialysis therapy 45.0 ± 45.2 months, not vaccinated against influenza; and Group C-63 healthy patients, mean age 44.1 ± 21.2 years, vaccinated against influenza - control group. The vaccinated patients (Groups A & C) received a single dose of Agrippal influenza vaccine (Novartis) containing hemagglutinin from three strains of the influenza virus: A/Brisbane/59/2007 (H1N1), A/Brisbane/10/2007 (H3N2), and B/Brisbane/60/2008. The serological response to vaccination was assessed from antihemagglutinin (anti-HA) and antineuraminidase antibody assays (anti-NA). We found that the protection level of antibodies (protection rate) against H1 was only 40% among the vaccinated hemodialysis patients, as opposed to 65% in controls. The level of anti-H3 antibodies was similar in both groups of vaccines; 68% in dialysis patients and 75% in controls. The level of anti-HB antibodies was higher in the dialysis patient than in controls; 70% vs. 38%, respectively. The response rate to H1 antigen a month after vaccination was almost twice lower in the hemodialysis patients than in healthy controls vaccinated against influenza; 37% vs. 65%, respectively. We conclude that there is a rather insufficient serological response in the group of hemodialysis patients vaccinated with a single dose of influenza vaccine.

Effectiveness of influenza vaccine in patients on hemodialysis - a review

The influenza virus is one of the most common causes of viral respiratory tract infections. Some chronic diseases predispose to a severe course of the disease and increase the risk of complications and death. To minimize the risk of infection and complications, care of patients with increased risk should include prophylactic measures such as the administration of a seasonal influenza vaccine. An influenza vaccine is the best and cheapest method of influenza prevention. It is indicated for patients with chronic kidney disease, both during conservative treatment and renal replacement therapy. Many studies that have assessed the efficacy of an influenza vaccine in patients on hemodialysis have found that immune deficiency predisposes these patients to infection and a severe course of the disease. Because the immune response to a standard influenza vaccine in this population is weak, the studies covered many aspects of vaccination, including the need for a booster dose. Unlike in a healthy population, the efficacy of an influenza vaccine in patients on hemodialysis might be insufficient; however, the vaccine is still able to induce immunity in a significant number of patients. Considering the latest data and the results of studies described above, the recommendation of a seasonal influenza vaccine should be obligatory in all hemodialysis patients. This paper is based on original articles available from Medline database. The most recent and most significant literature on the influenza vaccine in patients on hemodialysis has been reviewed.

Combined autologous bone marrow mononuclear cell and gene therapy as the last resort for patients with critical limb ischemia.

Introduction Our study was designed to investigate the safety and efficacy of combined autologous bone marrow mononuclear cell (MNC) and gene therapy in comparison to conventional drug therapy in patients with critical limb ischemia (CLI). Material and methods Thirty-two patients with CLI persisting for 12–48 months (average time 27.5 months) were randomized into 2 groups, each group consisting of 16 patients. In the first group, administration of autologous bone marrow MNC and vascular endothelial growth factor (VEGF) plasmid was performed. The patients from the second group were treated pharmacologically with pentoxifylline. Ankle-brachial index (ABI) was measured and angiography was performed before and finally 3 months after treatment. The pain was evaluated using the Visual Analog Scale (VAS) before and after 3 months. Results Ankle-brachial index improved significantly from 0.29 ±0.21 to 0.52 ±0.23 (p < 0.001) in 12 patients (75.0%) 3 months after the experimental therapy in group 1. In this group angiography showed the development of collateral vessels. Ischemic ulcers healed completely in 11 patients (68.75%). In group 2 the ABI did not improve in any patient; moreover the complete healing of skin ulcers was not found in any of the patients of this group. Amputation was performed in 4 (25.0%) patients in group 1, and in 8 patients (50%) from group 2. Conclusions These data after 3-month follow-up indicate that intramuscular injection of MNC combined with gene therapy in patients with chronic CLI is safe, and a more feasible and effective method of treatment than the conventional therapy. However, both therapies are limited by the degree of microcirculation damage.

Usage of Medical Internet and E-Health Services by the Elderly

Internet and e-health services have a substantial potential to support efficient and effective care for the elderly. The aim of the study was to investigate the use of Internet for health-related purposes among Polish elderly, the frequency and reasons of use, the importance of e-health services, and factors affecting their use. A total of 242 elderly at the age of ≥60 years were selected from the Polish population by random sampling. Data collection was carried out by phone interviews in October-November 2012. The study shows that the Internet was ever used by 32% of the elderly and 1/5 claimed a regular use. Among the Internet users, 81% of older people used it to obtain information about health or illness. The Internet was one of the less important sources of information (important for 27% of respondents), face to face contact with health professionals and family and friends are still the most required source of medical information (75%). Only 7% of elderly Internet users approached the family physician, specialists, or other health professionals over the Internet. Factors that positively affected the use of Internet among elderly were male gender, younger age, higher education, living with family, mobile phone use, and a subjective assessment of ones own health as good. The doctors provision of Internet-based services was important in the opinion of approximately 1/4 of older people. We conclude that the development of information and communications technology (ICT) tools increasingly meets the evolving needs of patients in the field of e-health. More and more elderly become beneficiaries of these services.

Prognostic value of tissue factor in patients with abdominal aortic and iliac arterial aneurysms - preliminary study.

Introduction The decision on the time and choice of strategy of treatment of abdominal aortic aneurysm must be especially carefully balanced. The aim of the study was to evaluate the tissue factor (TF) plasma level as a potential factor useful in anticipation of abdominal aortic aneurysm and/or iliac arterial aneurysm via comparison of plasma TF level in patients with ruptured and non-ruptured aneurysms. Material and methods The study included 33 patients with aneurysm (17 operated on electively because of non-ruptured aneurysm and 16 operated on emergently due to ruptured aneurysm), 33 claudicant patients with atherosclerosis of the abdominal aorta and iliac arteries with normal diameter of arteries, and 30 healthy controls. Plasma TF level was assessed by ELISA method using the IMUBIND Tissue Factor ELISA Kit (American Diagnostica Inc.). Results The study showed an increased TF level in patients with aneurysm (134 ±54 pg/ml) and in patients with atherosclerosis without concomitant aneurysm (91 ±30 pg/ml) in comparison with the control group (62 ±20 pg/ml), respectively p < 0.001 and p = 0.008. A significantly higher TF plasma level was observed in patients with ruptured abdominal aortic aneurysms (160 ±57 pg/ml) as compared to patients with non-ruptured aortic aneurysms (109 ±39 pg/ml) or peripheral arterial occlusive disease (91 ±30 pg/ml), respectively p < 0.001 and p < 0.001. The difference in TF level between the group with non-ruptured aortic aneurysms (109 ±39 pg/ml) and the patients with atherosclerosis without aneurysm (91 ±30 pg/ml) was not statistically significant. Conclusions No difference in TF level between patients with non-ruptured AAA/IAA and patients with aortic and iliac atherosclerosis without aneurysm indicates that an increased TF plasma level is not specific for any of the above-mentioned vascular pathologies.

The rs1800471 Polymorphism of TGFB1 Gene, Serum TGF-Beta1 Level and Chronic Kidney Disease Progression

The aim of the study was to investigate whether rs1800471 polymorphism in TGFB1 gene is associated with the development and progression of non-diabetic chronic kidney disease. Moreover, we examined the serum TGF-beta1 concentration and its association with that polymorphism and progression of the disease. We applied two different methodological approaches. Firstly, a family based study was carried out, comprised of 109 patients with non-diabetic chronic kidney disease and their 218 healthy parents, using the transmission/disequilibrium test. The rs1800471 polymorphism and serum TGF-beta1 level were determined in all subjects. Serum TGF-beta1 concentration was also measured in 40 healthy controls. Secondly, we performed a case-control orientated study to determine whether rs1800471 polymorphism and other factors influence the progression of renal impairment. We found no relationships between rs1800471 polymorphism allele transfer and the incidence or progression of non-diabetic chronic kidney disease. We found, however, that the serum TGF-beta1 was significantly higher in patients than in controls. In conclusion, rs1800471 polymorphism in TGFB1 gene does not have an impact on the development and progression of non-diabetic chronic kidney disease caused by primary glomerulopathy and chronic interstitial nephritis. The increased serum TGF-beta1 concentration in such patients suggests its role in the pathomechanism of the disease. Circulating TGF-beta1 level is determined in a multifactorial way, not by rs1800471 polymorphism in TGFB1 gene.

Coexistence of Chronic Bronchitis in Chronic Obstructive Lung Disease

The incidence of chronic obstructive pulmonary disease (COPD) is on the rise worldwide. Chronic bronchitis is a frequent accompaniment of COPD, which increases the burden of COPD in affected individuals. The aim of this study was to characterize the phenotype of chronic bronchitis in COPD patients. The study was based on the survey data retrospectively retrieved from the Action Health-Lung Cancer Prophylaxis and Health Care Improvement screening program that concerned all the inhabitants, aged over 40, of the Proszowice administrative region situated in the Lesser Poland Voivodeship in southern Poland. Participants with the symptoms suggestive of a lung disease were subject to further evaluation. The findings were that 546 (13.3%) out of the 4105 individuals displayed spirometry features of COPD. Symptoms of chronic bronchitis were present in 92 (16.8%) out of the COPD afflicted persons. Chronic bronchitis was commoner in current smokers and its incidence increased with increasing severity of airway obstruction. In multivariate analysis, chronic bronchitis was independently related to lower FEV1, FVC, FEV1/FVC, and to dyspnea. In regression model, factors related to increased risk of chronic bronchitis were current smoking, asthma, and lower lung function. We conclude that COPD with coexisting chronic bronchitis is linked to severer dyspnea and worse lung function. Current smoking, asthma, and lower lung function are related to increased risk of chronic bronchitis accompanying COPD.

Status of etoricoxib in the treatment of rheumatic diseases. Expert panel opinion

Pain is one of the most disabling symptoms of rheumatoid diseases. Patients with pain secondary to osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis (AS) or gout require effective analgesic treatment, and the physician’s task is to select a drug that is best suited for an individual patient. The choice of pharmacotherapy should be based both on drug potency and clinical efficacy, and its safety profile, particularly in the elderly population, as the number of comorbidities (and hence the risk of treatment complications and drug interactions) rises with age. In cases involving a high risk of gastrointestinal complications or concerns about hepatotoxicity, with a low cardiovascular risk, the first-line nonsteroidal anti-inflammatory drugs to consider should be coxibs including etoricoxib.

Role of vascular endothelial growth factor in inducing production of angiopoetin-1 - in vivo study in Fisher rats

The aim of the study was to investigate how an intramuscular injection of plasmids with genes coding various pro-angiogenic factors: angiopoetin-1 (ANGPT1), vascular endothelial growth factor (VEGF165) and hepatic growth factor (HGF), influences the production of ANGPT1. 40 Healthy Fisher rats received i.m. injections containing plasmids encoding pro-angiogenic genes in thigh muscles. They were divided into four equal groups. The first group received the plANGPT1 plasmid and the second group- the pIRES/ANGPT1/VEGF165 bicistronic plasmid. The pIRES/VEGF165/HGF bicistronic plasmid was administered to the third group and an empty plasmid (control group) to the fourth group. The animals were euthanized after 12 weeks. In each group, the number of vessels stained with the anti-ANGPT1 antibody was assessed under an optical microscope. The anti-ANGPT1 antibodies stained the vessels in all the groups. There were on average 14.1 ±2.3 vessels in the the plANGPT1 group, 32.5 ±10.5 in the pl/RESANGPT1/VEGF group and 30.8 ±13.3 in the plRES/HGV/VEGF group. There were on average 7.3 ±2.3 stained vessels (p < 0.0001) in the control group . The VEGF plays a role in the induction of the production of ANGPT1. The administration of plasmids only encoding ANGPT1 does not induce its production.