Maciej Kajor

Serum chemerin and vaspin in non-alcoholic fatty liver disease.

Abstract Objective. Chemerin and vaspin are new adipokines which may modulate inflammatory response and insulin sensitivity in non-alcoholic fatty liver disease (NAFLD). The aims of this study were to assess: (1) circulating levels of chemerin and vaspin and their association with liver histology and markers of liver injury in NAFLD patients; and (2) the relationship between the analyzed adipokines and insulin resistance. Material and methods. A total of 41 NAFLD patients with body mass index (BMI) 30.4 ± 3.3 kg/m2 [20 with non-alcoholic steatohepatitis (NASH) and BMI 30.3 ± 3.3 kg/m2 and 21 with simple steatosis/uncertain NASH (SS/UN) and BMI 30.5 ± 3.4 kg/m2] and 10 healthy volunteers with BMI 24.0 ± 2.9 kg/m2 were included in the study. Results. Serum chemerin concentration was significantly higher in NAFLD patients compared to healthy volunteers (p = 0.009). Serum chemerin was significantly higher in patients with NASH compared to patients with SS/UN (p = 0.009). The homeostasis model assessment for insulin resistance (HOMA-IR) value was higher in patients with NASH than in patients with SS/UN (p = 0.01). Serum chemerin and HOMA-IR were positively associated with NAFLD activity score (r = 0.40, p = 0.02; and r = 0.43, p = 0.008, respectively). Serum chemerin was associated with hepatocyte ballooning degeneration (r = 0.37; p = 0.03), total cholesterol (r = 0.45; p = 0.008) and diastolic blood pressure (r = 0.41; p = 0.02). HOMA-IR was related to fibrosis stage (r = 0.51; p = 0.001) and inflammatory activity grade in portal tracts (r = 0.40; p = 0.01). Serum vaspin correlated with hepatocyte ballooning degeneration (r = 0.31; p = 0.04), alanine aminotransferase and aspartate aminotransferase (r = 0.33, p = 0.03; and r = 0.32, p = 0.04, respectively) and diastolic blood pressure (r = 0.39, p = 0.01). Conclusions. This study shows for the first time that chemerin and vaspin serum concentrations are altered in patients with NAFLD. The analyzed adipokines appear to play a pivotal role in the pathogenesis of NAFLD, not only as regulators of insulin sensitivity, but also as mediators of the inflammatory process.

Validation of the BARD scoring system in Polish patients with nonalcoholic fatty liver disease (NAFLD)

AbtractBackgroundNonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver diseases, ranging from pure steatosis to nonalcoholic steatohepatitis (NASH), and eventually to liver cirrhosis with its complications. Identifying advanced fibrosis in patients is crucial to evaluating prognosis and possible therapeutic intervention. A novel, simple, and highly accurate scoring system called BARD, which identifies patients with NAFLD and without significant fibrosis, has been recently introduced and validated in North America..The aim of this study is to validate the BARD scoring system in a Polish cohort with NAFLD.MethodsA group of 104 Caucasians with biopsy-proven NAFLD were included in this study. Fibrosis in liver biopsies was evaluated according to the Histological Scoring System for Nonalcoholic Fatty Liver Disease. The BARD scoring system was assessed according to Harrison et al.: BMI ≥ 28 = 1 point, AST/ALT ratio (AAR) ≥ 0.8 = 2 points, type 2 diabetes mellitus = 1point.ResultsAge over 50 and AAR over 0.8 showed, respectively, a moderate and strong association with advanced fibrosis. A BARD score of 2-4 points was associated with F3 or F4 stages of fibrosis with an odds ratio of 17.333 (95% Cl; 3,639 - 82.558) and negative predictive value of 97%.ConclusionOur results demonstrate that the BARD scoring system has value in the non-invasive diagnosis of advanced fibrosis in NAFLD patients. The vast majority of patients with NAFLD would avoid liver biopsy if BARD was broadly introduced into the clinic.

NBL1 and anillin (ANLN) genes over-expression in pancreatic carcinoma

The aim of the study was to analyze the gene expression profile of pancreatic cancer to derive novel molecular markers of this malignancy. The snap-frozen or RNA-later preserved samples of 18 pancreatic adenocarcinomas, 5 chronic pancreatitis cases and 6 specimens of grossly normal pancreas were used for microarray analysis by HG-U133 Plus 2.0 oligonucleotide Affymetrix arrays. Validation was carried out by real-time quantitative PCR (Q-PCR) in the set of 66 samples: 31 of pancreatic cancer, 14 of chronic pancreatitis and 21 of macroscopically unchanged pancreas. By Principal Component Analysis of the microarray data we found a very consistent expression pattern of normal samples and a less homogenous one in chronic pancreatitis. By supervised comparison (corrected p-value 0.001) we observed 11094 probesets differentiating between cancer and normal samples, while only seventy six probesets were significant for difference between cancer and chronic pancreatitis. The only gene occurring within the best 10 genes in both comparisons was S100 calcium binding protein P (S100P), already indicated for its utility as pancreatic cancer marker by earlier microarray-based studies. For validation we selected two genes which appeared as valuable candidates for molecular markers of pancreatic cancer: neuroblastoma, suppression of tumorigenicity 1 (NBL1) and anillin (ANLN). By Q-PCR, we confirmed statistically significant differences in these genes with a 9.5 fold-change difference between NBL1 expression in cancer/normal comparison and a relatively modest difference between cancer and pancreatitis. For ANLN even more distinct differences were observed (cancer/normal 19.8-fold, cancer/pancreatitis 4.0-fold). NBL1 and anillin are promising markers for pancreatic carcinoma molecular diagnostics.

Diazoxide protects myocardial mitochondria, metabolism, and function during cardiac surgery: A double-blind randomized feasibility study of diazoxide-supplemented cardioplegia

OBJECTIVES The study was designed to assess whether diazoxide-mediated cardioprotection might be used in human subjects during cardiac surgery. METHODS Forty patients undergoing coronary artery bypass grafting were randomized to receive intermittent warm blood antegrade cardioplegia supplemented with either diazoxide (100 micromol/L) or placebo (n = 20 in each group). Mitochondria were assessed before and after ischemia and reperfusion in myocardial biopsy specimens. Myocardial oxygen and glucose and lactic acid extraction ratios were measured before ischemia and in the first 20 minutes of reperfusion. Hemodynamic data were collected, and troponin I, creatine kinase-MB, and N-terminal prohormone brain natriuretic peptide levels were measured. All outcomes were analyzed by using mixed-effects modeling for repeated measures. RESULTS No deaths, strokes, or infarcts were observed. Patients received, on average, 36.2 +/- 1.2 mg of diazoxide and 37.3 +/- 1.9 mg of placebo (P = .6). Diazoxide added to cardioplegia prevented mitochondrial swelling (8899 +/- 474 vs 9273 +/- 688 pixels before and after the procedure, respectively; P = .6) compared with that seen in the placebo group (8474 +/- 163 vs 11,357 +/- 759 pixels, P = .004). No oxygen debt was observed in the diazoxide group. Glucose consumption and lactic acid production returned to preischemic values faster in the diazoxide group. The following hemodynamic parameters differed between the diazoxide and placebo groups, respectively, in the postoperative period: cardiac index, 3.0 +/- 0.09 versus 2.6 +/- 0.09 L . min(-1) . m(-2) (P = .002); left cardiac work index, 2.81 +/- 0.07 versus 2.31 +/- 0.07 kg/m(2) (P < .001); oxygen delivery index, 420 +/- 14 versus 377 +/- 13 mL . min(-1) . m(-2) (P = .03); and oxygen extraction ratio, 29.3% +/- 1.1% versus 32.6% +/- 1.1% (P = .02). Postoperative myocardial enzyme levels did not differ, but N-terminal prohormone brain natriuretic peptide levels were lower in the diazoxide group (120 +/- 27 vs 192 +/- 29 pg/mL, P = .04). CONCLUSIONS Supplementing blood cardioplegia with diazoxide is safe and improves myocardial protection during cardiac surgery, possibly through its influence on the mitochondria.

Usefulness of Faecal Calprotectin Measurement in Children with Various Types of Inflammatory Bowel Disease

Introduction. The aim of the study was to assess the usefulness of the FC measurement in children with various types of IBD and relation to the disease activity. Patients and Methods. 91 patients (49 boys: 53.85% and 42 girls: 46.15%, mean age: 13.38 years, range 6–18 years) were included in the analysis. Patients were divided into the groups: B1—24 children with CD, B2—16 patients with UC, and a group comprising 31 children with other types of colitis; the control group (K) comprised 20 healthy children. FC was assayed by ELISA method, using Phical test (Calpro). Results. The mean faecal calprotectin concentrations were higher in children with CD and UC as compared to healthy controls, patients with eosinophilic, lymphocytic, and nonspecific colitis. A positive correlation was observed between FC concentrations and the disease activity (the PCDAI scale, the Truelove-Witts Scale, and the endoscopic Rachmilewitz Index). Conclusion. It seems that the FC concentrations can be a useful, safe, and noninvasive test in children suspected for IBD, since FC concentration is higher in children with CD and UC than in patients with other inflammatory diseases.

Expression, localization and systemic concentration of vascular endothelial growth factor (VEGF) and its receptors in patients with ulcerative colitis.

Vascular endothelial grow factor (VEGF) promotes angiogenesis by activating the specific receptors KDR and Flt-1. We investigate the expression of genes encoding VEGF and its receptors KDR and Flt- 1 by RT-QPCR reaction using Quanti Tect SYBR Green RT-PCR in patients with active and inactive ulcerative colitis (UC) and control subjects. The localization and level of VEGF protein and its receptors protein in intestinal tissue were estimated by immunohistochemistry. VEGF concentration in serum and plasma was determined by ELISA. We found a significant increase of VEGF gene expression and increase expression of genes encoding receptor Flt-1 in patients with active UC when compared with controls, but KDR was present in trace amount. VEGF and Flt-1 proteins were colocalized in enterocytes as well as in endothelium and muscularis layer of the intestine. The specific staining reaction for VEGF protein as well as for Flt-1 protein was significantly higher in active UC compared with controls. Serum level of VEGF was significantly higher in active UC patients as compared with inactive UC patients as well as with controls. The plasma VEGF level was found to be significantly higher in active UC patients as compared with controls. The increase of gene expression as well as protein level for VEGF and its receptor in UC - inflamed colon, and VEGF action via Flt-1 receptor may have a functional role in UC. Increased VEGF levels in both serum and plasma in active UC patients may reflect VEGF overexpression in intestinal inflammatory tissue.

Laboratory-based scoring system for prediction of hepatic inflammatory activity in patients with autoimmune hepatitis

In autoimmune hepatitis (AIH), inflammation is closely related to fibrosis. Although transaminase levels are commonly used to assess hepatic inflammation, they may not relate directly to the histology. We developed a noninvasive diagnostic score as an alternative to liver biopsy to help optimize treatment for AIH and monitor disease progress.

Schwannomalike mixed tumor of the parotid gland: a case report.

BACKGROUND Schwannomalike mixed tumor is a rare benign tumor of the parotid glands. CASE A 75-year-old woman presented with a tumor 3 cm in diameter localized in her left parotid gland. Fine needle aspiration (FNA) of the lesion revealed 2 types of cells: 1 with elongated, wavy, hyperchromatic nuclei and a scant cytoplasmic border and 1 with larger, weakly staining nuclei and more abundant cytoplasm. Morphologic examinations were performed. CONCLUSION FNA cytology was very useful in the diagnosis of this rare tumor of the parotid gland.

Surveyor Nuclease Detection of Mutations and Polymorphisms of mtDNA in Children

Mitochondrial encephalomyopathies are complex disorders with wide range of clinical manifestations. Particularly time-consuming is the identification of mutations in mitochondrial DNA. A group of 20 children with clinical manifestations of mitochondrial encephalomyopathies was selected for molecular studies. The aims were (a) to identify mutations in mtDNA isolated from muscle and (b) to verify detected mutations in DNA isolated from blood, in order to assess the utility of a Surveyor nuclease assay kit for patient screening. The most common changes found were polymorphisms, including a few missense mutations altering the amino acid sequence of mitochondrial proteins. In two boys with MELAS (i.e., mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), a mutation A→G3243 was detected in the tRNALeu gene of mtDNA isolated from muscle and blood. In one boy, the carrier status of his mother was confirmed, based on molecular analysis of DNA isolated from blood. A method using Surveyor nuclease allows systematic screening for small mutations in mtDNA, using as its source blood of the patients and asymptomatic carriers. The method still requires confirmation studying a larger group. In some patients, the use of this method should precede and might limit indications for traumatic muscle and skin biopsy.

Gruźlica narządów głowy i szyi – wciąż aktualny problem w praktyce laryngologicznej ☆

Summary Introduction It is estimated that between XVI and XIX century one fourth of European population died of tuberculosis. Nowadays tuberculosis is still one of the most important infectious diseases. In 2009 estimately 9 million new cases were registered worldwide, mortality due tuberculosis reached 1.5 million. In Poland extrapulmonary tuberculosis is rare (7% of overall morbidity) and most commonly affects pleura, lymph nodes, bones, joints and genitourinary system. Head and neck tuberculosis is rare and causes many diagnostics problems. Methods Retrospective analysis of case histories of patients admitted to ENT Department of Silesian Medical University in Katowice. Results Between 1993 and 2010 four cases of head and neck tuberculosis were diagnosed in our Clinic. Two of patients were admitted to the hospital with symptoms of laryngeal tumor such as difficulty in swallowing. During direct laryngoscopy tissue specimens were taken. Examination of the third patient showed tumor located below left angle of mandibule. During superficial parotidectomy tumor was removed. In the fourth registered case tuberculosis manifested as tumor of nasopharynx. In every case which is mentioned above pathology reports revealed epithelioid cell granulomas with caseous necrosis typical for tuberculosis. Patients underwent tuberculostatic treatment. Conclusion Rare occurence and lack of characteristic symptoms of head and neck tuberculosis often lead to misdiagnosis. Histopathological examination is the most important diagnostic procedure. Microbiological examination is difficult in extrapulmonary tuberculosis, because of low concentration of pathogens in specimens. Tuberculostatic therapy is the leading method of treatment in every case of tuberculosis.