MicroRNAs as potential markers of parenteral nutrition associated liver disease in adult patients.

Parenteral nutrition-associated liver disease (PNALD) is a severe complication in patients completely dependent on parenteral nutrition (PN). The gold diagnostic standard, liver biopsy, is associated with significant health risk and therefore its use is limited. MicroRNAs (miRNAs) are small non-coding regulatory RNA molecules with highly tissue-specific expression and the secreted miRNAs may serve as non-invasive diagnostic biomarkers. The aim of this study was to evaluate the expression of a panel of specific miRNAs associated with liver diseases of different origin in PN-dependent adult patients in order to design miRNA panel enabling to precise monitoring of PNALD progression. Twelve PN-dependent patients with short bowel syndrome (SBS) were monitored on three/four-month basis for up to 24 months. Forty-five age- and sex-matched subjects without any known liver pathology served as controls. Specific miRNAs expression was determined by RT-qPCR using TaqMan probes (Thermofisher). Liver function test parameters were determined in certified clinical laboratories. Six of the tested miRNAs exhibited significantly altered expression compared with healthy controls, three of them (MIR122, MIR1273g, and MIR500a) were upregulated while three were down-regulated (MIR505, MIR199a, MIR139). MIR122 positively correlated with serum AST and ALT activities while MIR1273g positively correlated with serum CRP concentration and GGT activity. MIR505, MIR199a, and MIR139 negatively correlated with serum GGT activity. Fluctuation of these parameters well paralleled serum miRNA concentrations in all patients throughout the whole observation period. We identified six miRNAs whose serum concentrations are significantly altered in PN-dependent patients with PNALD and correlate with markers of inflammation, cholestasis or hepatic injury. Their reliability as markers of PNALD progression needs to be further evaluated.

[A detailed study of colon polyps]. / Podrobná studie o polypech tlustého streva.

UNLABELLED: INTRODUCTION, STUDY AIM: Colorectal carcinoma is one of the most frequent malignancies. Most frequently, neoplasms, including malignant precursors, are in the form of polyps, although these might be of a non-tumour origin. The aim of this prospective multicentre study was to provide an overview of coloscopic identification and biological nature of polyps. RESULTS: 3,400 consecutive coloscopies performed between 2009 and 2010 were analyzed. At different centres, the top of the cecum was reached in 89% to 93% and terminal ileum in 73% to 87% of cases. In the above 40 age group, 26.6% were screening coloscopies. The mean age of the above 40 patients was 56 years. The incidence of potential neoplastic lesions (polyps, carcinomas), advanced adenomas and carcinomas were: 7.8 %, 0.8 % and 0.16 %, respectively, in the above 40 age group, 41.5 %, 9.8 % and 1.6 %, respectively, in the 40-50 years age group and 70.5 %, 31.3 % and 6.8 %, respectively, in the above 50 age group. The incidence of tubular adenoma and hyperplastic polyps was 23.9% and 66.2%, respectively, in the below 40 age group and 53.1% and 26.1% in the above 50 age group. 57.8% of advances neoplasms were located in the rectosigmoid a descendent colon. The incidence ratio for adenomas and hyperplastic polyps was 76.6% and 14%, respectively, for rectosigmoid colon, 63.6 and 17.4 %, respectively, for descendent colon, 63.6 and 11.4 % for traverse colon and 63,4 a 17,9 %, respectively, for cecum and ascendant colon. The incidence of tubulovillous adenomas and hyperplastic polyps in pedunculated polyps larger than 1 cm was 19.4 % and 20.4 %, respectively, and 34.2 % and 13.1 %, respectively, in other polyps. The incidence of potential lesions (polyps and carcinomas), advanced adenomas, carcinomas and advanced neoplasms was 66.7 %, 23.1 %, 5.8 % and 28.9 %, respectively, in women and 63.1 %, 30.0 %, 5.7 % and 34.7 %, respectively, in men. CONCLUSION: The top of the cecum was reached in a higher proportion of cases than required, although this was lower than in the majority of other recent studies. Terminal ileum was reached in high number of cases. The incidence of polyps and neoplasms rose sharply from 40 years of age. Therefore, the screening threshold should be extended to the below 50 age group. Hyperplastic polyps predominated in younger age and adenomas in the above 40 age group. Histological profile was similar and did not suggest importantly different pathogenesis with respect to localization. There were relatively fewer adenomas and more hyperplastic polyps in pedunculated polyps and vice verse in other types of polyps, suggesting a higher risk associated with non-pedunculated lesions. Both sexes differed less than suggested based on epidemiological statistics.

Urinary urea nitrogen excretion during the hyperinsulinemic euglycemic clamp in type 1 diabetic patients and healthy subjects.

The hyperinsulinemic euglycemic clamp (HEC) combined with indirect calorimetry (IC) is used for estimation of insulin-stimulated substrate utilization. Calculations are based on urinary urea nitrogen excretion (UE), which is influenced by correct urine collection. The aims of our study were to improve the timing of urine collection during the clamp and to test the effect of insulin on UE in patients with type 1 diabetes (DM1; n=11) and healthy subjects (C; n=11). Urine samples were collected (a) over 24 h divided into 3-h periods and (b) before and during two-step clamp (1 and 10 mIU.kg(-1).min(-1); period 1 and period 2) combined with IC. The UE during the clamp was corrected for changes in urea pool size (UEc). There were no significant differences in 24-h UE between C and DM1 and no circadian variation in UE in either group. During the clamp, serum urea decreased significantly in both groups (p<0.01). Therefore, UEc was significantly lower as compared to UE not adjusted for changes in urea pool size both in C (p<0.001) and DM1 (p<0.001). While UE did not change during the clamp, UEc decreased significantly in both groups (p<0.01). UEc during the clamp was significantly higher in DM1 compared to C both in period 1 (p<0.05) and period 2 (p<0.01). The UE over 24 h and UEc during the clamp were statistically different in both C and DM1. We conclude that urine collection performed during the clamp with UE adjusted for changes in urea pool size is the most suitable technique for measuring substrate utilization during the clamp both in DM1 and C. Urine collections during the clamp cannot be replaced either by 24-h sampling (periods I-VII) or by a single 24-h urine collection. Attenuated insulin-induced decrease in UEc in DM1 implicates the impaired insulin effect on proteolysis.

Effect of acute hyperinsulinaemia with and without angiotensin II type 1 receptor blockade on resistin and adiponectin concentrations and expressions in healthy subjects.

OBJECTIVE: The potential insulin-sensitizing function of angiotensin II type 1 receptor blockade (ARB) with regard to selected adipokines is not fully explained so far. Our study aimed to explore the influence of acute hyperinsulinaemia and acutely induced ARB on resistin and adiponectin concentrations and expressions in healthy subjects. DESIGN AND METHODS: Plasma adipokines were measured: 1) at 0, 30 and 240 min of hyperinsulinaemic (1 mU/kg per min) euglycaemic (5 mmol/l) clamp (HEC), and 2) during HEC after acute ARB (losartan 200 mg; AT-HEC) using the same protocol, in eight healthy subjects. Needle biopsy of abdominal s.c. fat was performed at 0, 30 and 240 min of both clamps to assess the adipokines' expressions. RESULTS: Comparing the glucose disposals of HEC and AT-HEC, no difference in insulin sensitivity was found. Plasma resistin increased equally during HEC and AT-HEC (P < 0.05). The expression of resistin in s.c. fat increased during HEC (P < 0.05), while no significant changes in expression were observed during AT-HEC. Plasma levels of adiponectin did not change during both clamps. Adiponectin expression increased during HEC (P < 0.05), while it did not change during AT-HEC. CONCLUSIONS: In healthy subjects, acute hyperinsulinaemia is associated with an increase in plasma resistin independently of ARB, while plasma adiponectin is not influenced by insulin or ARB. The expressions of both resistin and adiponectin in s.c. adipose tissue are stimulated by acute hyperinsulinaemia, whereas losartan attenuates their insulin-stimulated expressions. This suggests a potential effect of losartanon adipokines' expression.

[Transcutaneous oximetry in the diagnosis of ischemic disease of the lower extremities in diabetics]. / Transkutánní oxymetrie v diagnostice ischemické choroby dolních koncetin u diabetiku.

In diabetic patients with ischaemia of the lower extremities and mediocalcinosis the diagnosis of ischaemia is still difficult. One of the methods which give an objective idea of the microcirculation is transcutaneous oximetry. In the submitted paper the authors explain the principle and problems of assessment with recommendations for the practical application of the method, in particular in indication for angiography of the lower extremities in the presence of the diabetic foot syndrome with regard to probable spontaneous healing of defects and application of the method for following up the effect of revascularization operations.

Effect of daclizumab on inflammatory infiltrate in fine needle aspiration biopsy in patients after liver transplantation.

OBJECTIVES: FNAB is a cytological procedure enabling the monitoring of inflammatory cells in the graft, morphological modification of parenchymal cells, and expression of antigens on aspirated cells. The aim of the study was to evaluate whether Daclizumab influences the composition of inflammatory infiltrate and expression of HLA-DR antigens and intercellular adhesive molecule ICAM-1 on parenchymal cells. METHODS: Two groups of liver allograft recipients were included and they were treated with two different immunosuppressive protocols. The first group with quadruple immunosuppression therapy (Cyclosporine A, Mycophenolate mofetil, steroids, and Daclizumab). The second group with quadruple combination immunosuppression (Cyclosporine A, Azathioprine, steroids and ATG-Fresenius). FNAB and blood samples were collected simultaneously. Corrected increments of inflammatory cells were statistically evaluated as well as expression of HLA-DR antigens and ICAM-1 on parenchymal cells. RESULTS: FNAB specimens from the Daclizumab group demonstrated significantly lower values of the total corrected increment, the corrected increment of monocytes, number of blast cells per slide, and a lower number of ICAM-1 expressing parenchymal cells. CONCLUSION: We summarise that Daclizumab significantly reduces inflammatory cells in liver graft, as well as expression of ICAM-1 on parenchymal cells.

Correlation of FNAB with histology in human liver allografts. Regional experience.

OBJECTIVES: A total of 43 FNABs, corresponding blood specimens and conventional biopsies from 39 adult liver allograft recipients were analysed. The purpose of the present study was to determine whether results obtained by cytological and histological examination were concordant at the monitoring of liver allograft rejection within the first 5 weeks of the posttransplant period. RESULTS: When histology in 14 cases showed rejection, rejection was diagnosed in 12 out of 14 FNAB specimens. When in other 14 cases the rejection was absent histologically, FNAB was negative in 10 out of those 14 specimens (sensitivity 85.7%, specificity 71.4%). Cholestasis was demonstrated in biopsy and FNAB specimens with sensitivity 83% and specificity 86%. CONCLUSION: FNAB is a useful method for diagnosis of acute rejection in liver allograft during the early posttransplant period, as well as for evaluation of cholestasis. Results obtained by FNAB correlated well with results obtained by core-needle biopsy.

[Light chain deposition disease as a cause of renal failure]. / Nemoc z ukládání lehkých retezcu jako prícina renálního selhání.

The objective of the paper is to draw attention to a rare cause of rapidly progressing renal failure which developed in the course of four months as a result of light chain deposition disease. The authors submit two case-histories of the disease assessed by renal biopsy after previous clinical and laboratory suspicion of monoclonal gammapathy. In one patient in the sternal punctate plasmacytoma was diagnosed and in the second case it was not possible to detect any type of monoclonal gammapathy or another possible cause of disease. Renal failure was in both cases irreversible and both patients were enlisted in regular haemodialyzation treatment.