Malgorzata Zagozda

Lack of effect of the CD14 promoter gene C-159T polymorphism on nutritional status parameters in hemodialysis patients.

Summary Background CD14 is a membrane glycoprotein that acts as a co-receptor for the detection of bacterial lipopolysaccharide (LPS). Mutual interaction between CD14 and LPS plays an important role in the innate immune system. Increased serum soluble CD14 levels have been described in hemodialysis (HD) patients, and linked to increased mortality risk, inflammation and protein-energy wasting. The expression of CD14 may be influenced by CD14 promoter gene C-159T polymorphism. This study aimed to clarify the possible association between CD14 promoter gene C-159T polymorphism and nutritional status in hemodialysis patients. Material/Methods The study population consisted of 185 (104 males; 81 females) long-term HD patients treated in 5 dialysis centers. The control group consisted of 112 apparently healthy volunteers (32 males and 80 females). Nutritional status was assessed using a modified SGA scale, and anthropometric methods (BMI, WHR, waist, hip and mid-arm circumferences, biceps, triceps, subocular and subscapular skinfolds). Biochemical parameters evaluated included: CRP, albumin, creatinine, urea, cholesterol, triglycerides and TIBC. CD14 promoter gene C-159T polymorphism was determined by restriction fragment length polymorphism, after digestion of the PCR product with Hae III restriction endonuclease. Results Genotype and allele frequencies were similar to controls and compliant with Hardy-Weinberg equilibrium. No between-group differences were detected in measured variables with the exception of lower triglyceride levels in carriers of C allele in comparison to TT genotype. Conclusions CD14 promoter gene C-159T polymorphism does not seem to be associated with nutritional status parameters in HD patients. It does seem, however, to influence triglyceride blood levels.

An Overview of Genetic Changes and Risk of Pancreatic Ductal Adenocarcinoma

The pancreatic carcinoma is a leading cause of death in cancer carriers worldwide. The early diagnostic is difficult due to late stage during diagnosis, lack of characteristic symptoms and also multifactor basis. In cancer development take part both, environmental and genetic factors, alone or in conjunction with each other. The nonspecific biomarkers of cancers are a reason for the search for more accurate factors which allow for fast and personalized diagnostics. Some of cancers have identified molecular (metabolic, biochemical or genetic) markers but in most cases the only clue is patient`s interview and abnormal levels of organ functions markers. Possible genetic basis of cancer suggests to widen studies on connection between environmental factors with both, nuclear and mitochondrial, genes changes.

Bacteria of leg atheromatous arteries responsible for inflammation

BACKGROUND Ischaemia of the lower limbs is frequently followed by inflammation and, in advanced cases, necrosis of peripheral tissues. Whether this is caused by arterial hypoperfusion only or by the presence of bacteria in the arterial walI as well remains unclear. The aim of the study was to prove the presence and source of bacteria in arterial specimens and evaluate their chemotactic properties resulting in the formation of periarterial cellular infiltrates. MATERIALS AND METHODS Bacterial culture and testing for 16sRNA were performed in fragments of popliteal artery harvested from amputated limbs. Carotid artery plaques served as controls. Fragments of arteries were transplanted into scid mice to evaluate their chemotactic activity for macrophages. RESULTS a) higher prevalence of isolates and 16sRNA in atherosclerotic popliteal than carotid arteries, b) high density of plaque and periarterial infiltrates and mRNA level for pro-inflammatory cytokines in popliteal arteries, c) prevalent microbes were Staphylococcus aureus, S. epidermidis and Enterococci, d) foot skin and arterial bacterial phenotypes and DNA revealed evident similarities, and e) more intensive mouse macrophage accumulation in popliteal than carotid implants into scid mice. CONCLUSIONS The presence of bacteria in the lower limb arterial wall was documented. They may predispose to inflammation secondary to ischaemic changes.

Genetic Polymorphism and Messenger Ribonucleic Acid Concentrations of TNFα and TGFβ Genes in Patients with Chronic Lower Limb Infections

BACKGROUND The number of chronic lower limb infections and their complications as venous and diabetic ulcers and chronic calf dermatitis is increasing worldwide. The clinical course and outcome in the immune responses to infection have been shown to be associated with genetic polymorphisms. The aim of study was to investigate frequencies of chosen single nucleotide polymorphisms (SNPs) in TNFα and TGFβ genes in patients with chronic lower limb infections and evaluate expression of messenger ribonucleic acid (mRNA) concentrations in chronic leg ulcers. METHODS Patients were divided into three groups: (group A) chronic venous leg ulcers, (group B) chronic post-traumatic non-healing wounds, and (group C) infected ischemic necrosis of the foot. Blood donors comprised the control group. Detection of polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and gene expression by real-time PCR methods. RESULTS Patients in all groups showed higher frequency of TNFα gene polymorphism -308GG and lower frequency of -308GA genotypes than controls. The mutated homozygote AA was higher in groups A and B than in controls. The TGFβ74GG genotype was represented at highest values in group B. The GC genotype was found in all groups at a similar concentration lower than in controls. Genotypes TGFβ29TT and TC were represented at similar concentrations as controls. Analyses showed that the presence of the polymorphic allele -308A of TNFα gene was correlated with an increased concentration of gene expression in patients with chronic leg ulcers (group A). In the case of both TGFβ gene polymorphisms the presence of polymorphic allele C resulted in increased TGFβ gene expression. CONCLUSIONS Comparison of genotypes in polymorphic sites in TNFα and TGFβ genes with their expression concentrations showed that the presence of polymorphic alleles could predispose to increased production of their proteins. Patients with prolonged non-healing wounds should have their genotypes studied, and in cases of mutation, long-term antibiotic and immune protein supply should be considered.

M1873 TGFβ Polymorphism in Patients With Acute Pancreatitis (AP) in Association With Cytokine Level and Disease Severity

G A A b st ra ct s may limit its utility. Aims: To evaluate the potential usefulness of electrophysiological studies, ex vivo, on rectal biopsy samples as a surrogate marker for measurement of CFTR function. These results were compared to NPD results from the same subject. Methods: Intestinal Current Measurement (ICM) and NPD were performed on healthy controls (routine colonoscopy) and CF patients (sigmoidoscopy). Median values comprising the ICM (carbachol, histamine, and forskolin responses) and NPD (basal and chloride transport responses) tests were determined. For each response, the Wilcoxon rank sum test was applied to determine the ability of each measure to distinguish between CF and healthy controls. Results: ICM measurements demonstrated a median (interquartile range) carbachol response in healthy control subjects (n=29 subjects; 40 analyzable biopsies) of 11.1 (7.9, 20.75) μA/cm2, histamine response of 8.7 (5.0, 12.9) μA/cm2, and a forskolin response of 3.9 (2.3, 7.4) μA/cm2. These responses were inverted in CF subjects (n=8, 10 analyzable biopsies) with a mean carbachol response of -2.5 (-4.8, -1.6) μA/cm2, histamine of -1.0 (-1.6, 0) μA/cm2, and no forskolin response. Each of the ICM measurements effectively distinguished between CF and controls (p < 0.0001). NPD measurements demonstrated a median basal PD response in healthy control subjects (n=7) of -12.0 mV (13.5, -8.0) and a chloride transport response of 14.0 mV (12, 20.5). In CF subjects (n=8), the median values were -49.0 mV (-51.5, -42.5) and -2.0 mV (-3.0, 0), respectively. Similar to ICM, each of the NPD measurements distinguished between healthy controls and CF (p < 0.0005). Conclusions: ICM is equivalent to NPD in the ability to distinguish CF patients from healthy controls. Rectal biopsy studies, like NPD, allow measurement of CFTR mediated chloride transport which has the potential for use as a therapeutic endpoint for studies in CF patients. This is of particular importance in evaluating young children who are less likely to tolerate NPD.