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The rapid market changes and strong product individualization create the need for great flexibility of manufacturing management on new foundations, such as the Industry 4.0 model. Digital manufacturing is the basis for Industry 4.0, that have the following dimensions: (i) digital manufacturing based on advanced digital-oriented technologies, (ii) smart products (advanced manufacturing mode and new characteristics), and (iii) smart supply - chain (procurement of raw materials and delivery of finished products). Bidirectional exchange of information in collaborative manufacturing, using it exchange also for digital platforms of design of the innovative products. In this paper we are showing developed model of one Serbian digital factory model for Quality 4.0 (Q 4.0) , especially in workshop as a part of ERP/MES model.

Serbia is rapidly working on the development and implementation of digital manufacturing models in SMEs, through the national Industry 4.0 Platform. The aim is to create a pilot intelligent workshop which would be used to develop and showcase examples of best practice for digital manufacturing. Currently, most SMEs use CAD, CAM, ERP models, which form the basis for the development of the concept of digital manufacturing through cloud computing, BDA, IIoT and smart supply-chains, as elements of Industry 4.0. This paper gives a practical example of an SME with all the above-mentioned elements of digital manufacturing.

Cardioprotective abilities of procyanidins, might, at least in part, attribute to their vasodilator properties. The present study was undertaken to assess the vasorelaxant effect of procyanidin B2 on isolated human saphenous vein (HSV) and its underlying mechanisms. Procyanidin B2 relaxed phenylephrine-induced contraction of HSV rings in concentration-dependent manner. The relaxation was dependent on the presence of endothelium and was strongly affected by l-NAME, hydroxocobalamin or ODQ, the inhibitors of NO/cGMP pathway. Indomethacin significantly affected only the relaxation produced by the highest concentrations of procyanidin B2. Apamin and TRAM-34 combination, in the presence of l-NAME and indomethacin, did not additionally decreased procyanidin B2-induced relaxation. In the presence of K+ channel blockers, relaxation induced by procyanidin B2 was partially attenuated by 4-aminopyridine, significantly inhibited by glibenclamide and almost abolished by iberiotoxin. Procyanidin B2 also relaxed the contractions induced by phenylephrine or caffeine in Ca2+-free solution. Finally, nifedipine slightly, while thapsigargin strongly antagonized HSV relaxation. Our results indicate that procyanidin B2 induces endothelium-dependent relaxation of HSV, which results primarily from stimulation of NO production, as well K+ channels opening, especially BKCa, and partially KATP and KV. Regulation of the intracellular Ca2+ release and inhibition of Ca2+ influx probably contribute to procyanidin B2-induced relaxation. Keywords: Endothelium, Human saphenous vein, Procyanidin B2, Vasorelaxation, K+ channels, Ca2+ channels

Background and objectives: This study aimed to evaluate prognostic factors for post-recurrence survival in local and locally advanced colorectal cancer patients. Materials and Methods: A total of 273 patients with stage III and high-risk stage II colorectal cancer were prospectively enrolled. All patients underwent operative treatment of the primary tumor and adjuvant fluorouracil-based chemotherapy. Results: Over the three-year period (2008–2010), a cohort of 273 patients with stage III and high-risk stage II colorectal cancer had been screened. During follow up, 105 (38.5%) patients had disease recurrence. Survival rates 1-, 3- and 5-year after recurrence were 53.9, 18.2 and 6.5%, respectively, and the median post-recurrence survival time was 13 months. Survival analysis showed that age at diagnosis (p &lt, 0.01), gender (p &lt, 0.05), elevated postoperative Ca19-9 (p &lt, 0.01), tumor histology (adenocarcinoma vs. mucinous vs. signet ring tumors, p &lt, 0.01) and tumor stage (II vs. III, p &lt, 0.05) had a significant influence on post-recurrence survival. Recurrence interval and metastatic site were not related to survival following recurrence. Multivariate analysis showed that older age (HR 2.43), mucinous tumors (HR 1.51) and tumors expressing Ca19-9 at baseline (HR 3.51) were independently associated with survival following recurrence. Conclusions: Baseline patient and tumor characteristics largely predicted patient outcomes after disease recurrence. Recurrence intervals in local and locally advanced colorectal cancer were not found to be prognostic factors for post-recurrence survival. Older age, male gender, stage III and mucinous histology were poor prognostic factors after the disease had recurred. Stage II patients had remarkable post-recurrence survival compared to stage III patients.

Introduction. There is a rise of visceral leishmaniasis in immunocompromised patients due to increased availability of immunomodulatory drugs. In order to point at the occurrence of visceral leishmaniasis in patients with inflammatory bowel disease (IBD), we reported a case of female patient with a travel history to European Mediterranean countries, who was on immunosuppressive treatment due to ulcerative colitis. Case report. A 29-year-old female patient was admitted to hospital due to severe relapse of ulcerative colitis. Corticosteroid therapy was administered in addition to previous longterm azathioprine, with clinical response to the treatment. During the course of the disease she had recurrent high-grade fever with marked hepatosplenomegaly and pancytopenia. The diagnosis of leishmaniasis was established by positive serology tests and microscopic finding of amastigotes in bone marrow smears. The disseminated infection was responsive to treatment with liposomal amphotericin B, but therapy had to be discontinued due to urticarial rush. Subsequent therapy with antimony was administered, but it had to be stopped too due to liver toxicity. No further treatment for leishmaniasis was initiated as the clinical and laboratory data suggested that the patient had responded to the treatment. She was discharged from hospital in IBD remission and without signs of the infection. Conclusion. Visceral leishmaniasis should be considered in IBD patients with fever of unknown origin and relevant travel history in order to achieve favorable disease outcome.

The aim of the present study was to investigate and characterize vasorelaxant effect of procyanidin B2 on human internal mammary artery (HIMA) as one of the mechanisms of its protective effect against vascular risk. Procyanidin B2 induced strong concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Pretreatment with L-NAME, a NO synthase inhibitor, hydroxocobalamin, a NO scavenger, and ODQ, an inhibitor of soluble guanylate cyclase, significantly inhibited procyanidin B2-induced relaxation of HIMA, while indomethacin, a cyclooxygenase inhibitor, considerably reduced effects of low concentrations. Among K+ channel blockers, iberiotoxin, a selective blocker of large conductance Ca2+-activated K+ channels (BKCa), abolished procyanidin B2-induced relaxation, glibenclamide, a selective ATP-sensitive K+(K-ATP) channels blocker, induced partial inhibition, while 4-aminopyridine, a blocker of voltage-gated K+(K-V) channels, and TRAM-34, an inhibitor of intermediate-conductance Ca2+-activated K+(IKCa) channels, slightly reduced maximal relaxation of HIMA. Further, procyanidin B2 relaxed contraction induced by phenylephrine in Ca2+-free Krebs solution, but had no effect on contraction induced by caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca2+-ATPase inhibitor, significantly reduced relaxation of HIMA produced by procyanidin B2. These results demonstrate that procyanidin B2 produces endothelium-dependent relaxation of HIMA pre-contracted by phenylephrine. This effect is primarily the result of an increased NO synthesis and secretion by endothelial cells and partially of prostacyclin, although it involves activation of BKCa and K-ATP, as well as K-V and IKCa channels in high concentrations of procyanidin B2.

Introduction Findings from epidemiological studies indicate that polyphenols, widespread in human diet and with numerous biological activities, act cardioprotectively. Procyanidins are subclass of polyphenols with high content in commonly consumed foods and beverages, such as grapes, tea, chocolate, nuts and apples. Cardioprotective abilities of procyanidins, might, at least in part, attribute to their vasodilator properties. Purpose Because the exact mechanisms by which procyanidin B2 causes vasorelaxation are unclear, we aimed to investigate relaxant effect of procyanidin B2 on the isolated human internal mammary artery (HIMA) and its underlying mechanisms. Methods The HIMA segments were collected from patients suffering from coronary artery disease who were undergoing coronary artery bypass surgery and studied in organ bath. Results Procyanidin B2 induced strong concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Pretreatment with L-NAME, a NO synthase inhibitor, hydroxocobalamin, a NO scavenger, and ODQ, an inhibitor of soluble guanylate cyclase, significantly inhibited procyanidin B2-induced relaxation of HIMA, while indomethacin, a cyclooxygenase inhibitor, considerably reduced effects of low concentrations. Among K+ channel blockers, iberiotoxin, a selective blocker of large conductance Ca2+-activated K+ channels (BKCa), abolished procyanidin B2-induced relaxation, glibenclamide, a selective ATP-sensitive K+ (KATP) channel blocker, induced partial inhibition, while 4-aminopyridine, a blocker of voltage-gated K+ (KV) channels, and TRAM-34, an inhibitor of intermediate-conductance Ca2+-activated K+ (IKCa) channels, slightly reduced maximal relaxation of HIMA. Conclusion Our results demonstrate that, in HIMA, procyanidin B2 produces strong endothelium-dependent vasorelaxant effect. It seems that this relaxation is primarily the result of an increased NO synthesis and secretion by endothelial cells and partially of prostacyclin, although it involves activation of BKCa and KATP, as well as KV and IKCa channels in high concentrations of procyanidin B2. Acknowledgement/Funding The study was supported by a Scientific Research Grant (P175088) from Ministry of Science and Technology Serbia.

Intrahepatic cholestasis of pregnancy (ICP) is a gestation-specific liver disorder, defined most often as the onset of pruritus, usually from the third trimester of pregnancy, associated with abnormal liver test results and/or increased total serum bile acids and spontaneous relief after delivery. The 21-year-old patient was admitted to our ward in the 11th week of pregnancy due to raised liver enzymes. The first onset of pruritus and jaundice appeared a month before hospitalization. Immunology tests and Toxoplasma gondii were negative. We excluded viral etiology, while alpha-1-antitrypsin, serum and urine copper levels, and thyroid hormones were within the reference values. The patient denied she had taken any medicines and herbal preparations before and during pregnancy. Total bile acids in the serum were significantly elevated (242 μmol/L). The abdominal ultrasound revealed a regular finding. Liver biopsy suggested a cholestatic liver disorder. After a presentation of all risks, the patient decided to stop the pregnancy. After a month, the hepatogram was within the reference values. Very rarely an ICP can occur in early pregnancy (first trimester), which calls for close monitoring. The risk of serious adverse fetal outcomes and spontaneous preterm delivery is proportional with increased levels of maternal serum bile acid.

Inflammatory bowel disease (IBD), manifesting as Crohn's disease (CD) and ulcerative colitis (UC), is characterized by recurring episodes of inflammation in gastrointestinal tract, in which aberrant production of regulatory cytokine interleukin-10 (IL-10) presumably plays important role. Single nucleotide polymorphisms (SNPs) that affect IL-10 production, such as rs1800896 (G/A) at position -1082 and rs1800871 (C/T) at position -819 in the promoter region of the IL10 gene, have been associated with CD and/or UC, but the results were inconsistent. Another SNP that may alter IL-10 production, rs3024505 (C/T) located immediately downstream of the IL10 gene has been recently identified. T allele of rs3024505 was associated with both UC and CD in Western populations, but the studies from East European countries are lacking. Therefore, our aim was to assess the association of rs3024505, rs1800896 and rs1800871 with Serbian IBD patients. To this end, 107 CD and 99 UC patients and 255 healthy controls were genotyped. As a result, T allele of rs3024505 was associated with CD at allelic, genotypic (GT genotype) and haplotypic (GCCT haplotype) level, suggesting potential role of this variant in susceptibility to CD. In contrast, CD patients carrying C allele of rs3024505 had significantly increased risk of anemia and stricturing/penetrating behavior. No association was observed between rs3024505 and UC or SNPs in IL10 promoter region and any form of IBD. In conclusion, rs3024505 SNP flanking the IL10 gene is associated with susceptibility and severity of disease in Serbian CD patients, further validating its role as a potential biomarker in IBD.

In this study, we aimed to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human saphenous vein (HSV), as a part of its cardioprotective action, and to define the mechanisms underlying this vasorelaxation. (-)-Epicatechin induced a concentration-dependent relaxation of HSV pre-contracted by phenylephrine. Among K+ channel blockers, 4-aminopyridine, margatoxin, and iberiotoxin significantly inhibited relaxation of HSV, while glibenclamide considerably reduced effects of the high concentrations of (-)-epicatechin. Additionally, (-)-epicatechin relaxed contraction induced by 80 mM K+ , whereas in the presence of nifedipine produced partial relaxation of HSV rings pre-contracted by phenylephrine. In Ca2+ -free solution, (-)-epicatechin relaxed contraction induced by phenylephrine, but had no effect on contraction induced by caffeine. A sarcoplasmic reticulum Ca2+ -ATPase inhibitor, thapsigargin, significantly reduced relaxation of HSV produced by (-)-epicatechin. These results demonstrate that (-)-epicatechin produces endothelium-independent relaxation of isolated HSV rings. Vasorelaxation to (-)-epicatechin probably involves activation of 4-aminopyridine- and margatoxin-sensitive KV channels, BKCa channels, and at least partly, KATP channels. In addition, not only the inhibition of extracellular Ca2+ influx, but regulation of the intracellular Ca2+ release, via inositol-trisphosphate receptors and reuptake into sarcoplasmic reticulum, via stimulation of Ca2+ -ATPase, as well, most likely participate in (-)-epicatechin-induced relaxation of HSV.

Background: Data suggest cystatin C (CysC) levels and hepatic artery resistive index (HARI) correspond to the progression of chronic liver disease. We aimed to evaluate the clinical significance of these parameters in assessment of fibrosis in patients with liver cirrhosis. Methods: The cross-sectional study included 63 patients with liver cirrhosis. A control group consisted of 30 age- and gender-matched healthy persons. Results: We confirmed significantly higher values of CysC in patients with cirrhosis compared to control group (p = 0.036). Average value of HARI in the examined group was increased (0.72 ± 0.06) and there was the statistically significant difference compared to controls (0.66 ± 0.03) (p < 0.001). We found statistically significant correlation between HARI and CysC in the study group. Analyzing the possibility of distinguishing healthy subjects from patients with fibrosis, we have found that the area under the curve is far greater in the HARI index than CysC. Comparison of CysC among Child–Pugh stages and correlation with a model for end-stage liver disease (MELD) score showed statistically significant results. Conclusion: We confirmed HARI is a more accurate parameter than CysC in discriminating healthy subjects from patients with fibrosis, while CysC could be a better indicator of the stage of liver cirrhosis.

In this study, we aimed to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human saphenous vein (HSV), as a part of its cardioprotective action, and to define the mechanisms underlying this vasorelaxation. (-)-Epicatechin induced a concentration-dependent relaxation of HSV pre-contracted by phenylephrine. Among K

Lerimazoline is a sympathomimetic drug that belongs to the imidazoline class of compounds, and is used as a nasal decongestant. Studies on lerimazoline are rare, and its pharmacological profile is not completely understood. Here, we analyzed the affinity of lerimazoline for dopamine receptor D2, serotonin 5-HT1A and 5-HT2A receptors and alpha(1)-adrenoceptor, and investigated lerimazoline contractile effects in isolated rat thoracic aorta. We also determined the effect of several antagonists on the contractile response to lerimazoline, including prazosin (alpha(1)-adrenoceptor antagonist), RX 821002 and rauwolscine (alpha(2)-adrenoceptor antagonists), JP 1302 (alpha(2C)-adrenoceptor antagonist), methiothepin (non-selective 5-HT receptor antagonist), SB 224289 (5-HT1B receptor antagonist), BRL 15572 (5-HT1D receptor antagonist), and ketanserin (5-HT2A receptor antagonist). Lerimazoline displayed high affinity for the 5-HT1A receptor (Ki = 162.5 nM), similar to the previously reported affinity for the 5-HT1D receptor. Binding affinity estimates (Ki) for alpha(1), 5-HT2A, and D-2 receptors were 6656, 4202 and 3437.5 nM, respectively (the literature reported Ki for 5-HT1B receptor is 3480 nM). Lerimazoline caused concentration-dependent contractions in 70% of preparations, varying in the range between 40% and 55% of the maximal contraction elicited by phenylephrine. While prazosin reduced the maximum contractile response to lerimazoline, rauwolscine showed a non-significant trend in reduction of the response. Both ketanserin (10 nM and 1 mu M) and methiothepin strongly suppressed the maximum response to lerimazoline. Overall, our results suggest that 5-HT2A and, less distinctly, alpha(1)-adrenergic receptors are involved in the lerimazoline-induced contractions, which makes lerimazoline an "atypical" decongestant.

It is well known that physical activity and proper diet can have beneficial effects on health improvement, as a prevention and as a therapy of chronic non-communicable diseases. Pregnancy is a special period in the life of every woman. Therefore, you often ask yourself whether it is advisable to exercise during pregnancy, when and how much? This review article, by analyzing the available literature data, has tried to explain what form of physical activity is recommended during pregnancy, depending on the period of pregnancy, under what conditions pregnant women should exercise, what forms of physical activity they should avoid and when they should not to practice it. In addition, we analyzed the role of physical activity in the prevention of gestational diabetes, the most common metabolic disorder that occurs during pregnancy. Following the recommendations of the FITT principle outlined in this paper, controlled exercise conditions with a specialized trainer and nutritionist, regular moderate physical activity adapted to different periods of pregnancy, undoubtedly contributes to the maintenance and improvement of the musculoskeletal and cardiovascular system of the pregnant woman, better control of her body weight and improvement of her psychological state.

Bacground/Aim. Crohn's disease (CD) and ulcerative colitis (UC) are chronic, idiopathic, inflammatory diseases of the digestive tract. The aim of this study was to determine a possible correlation between the clinical parameters of the disease activity degree and the presence of extraintestinal manifestations with disease activity histopathological degree, in patients presented with CD and UC. Methods. This cross-sectional study included 134 patients (67 with CD and UC, respectively) treated at the Clinic of Gastroenterology, Clinical Center of Serbia, Belgrade. After clinical, laboratory, endoscopic, histopathologic and radiologic diagnostics, the patients were divided into two groups according to their histopathological activity. The group I comprised 79 patients whose values of five-grade histopathological activity were less than 5 (45 with CD and 34 with UC), while the group II consisted of 55 patients with the values higher than 5 (22 with CD and 33 with UC). The CD activity index (CDAI) and Truelove and Witts' scale of UC were used for clinical evaluation of the disease activity. Results. CD extraintestinal manifestations were present in 28.9% and 63.6% of the patients in the groups I and II, respectively (p < 0.05). Comparison of the mean CDAI values found a significant difference between these two patients groups (the group I: 190.0 ? 83.0, the group II: 263.4 ? 97.6; p < 0.05). No correlation of extraintestinal manifestations of the disease, Truelove and Witts' scale and histological activity was found in UC patients (p > 0.05). Conclusion. In the patients presented with CD, the extraintestinal manifestations with higher CDAI suggested a higher degree of histopathological activity. On the contrary, in the UC patients, Truelove and Witts' scale and extraintestinal manifestations were not valid predictors of the disease histopathological activity.

Inflammatory bowel disease (IBD), manifesting as Crohn's disease (CD) and ulcerative colitis (UC), is characterized by recurring episodes of inflammation in gastrointestinal tract, in which aberrant production of regulatory cytokine interleukin-10 (IL-10) presumably plays important role. Single nucleotide polymorphisms (SNPs) that affect IL-10 production, such as rs1800896 (G/A) at position -1082 and rs1800871 (C/T) at position -819 in the promoter region of the IL10 gene, have been associated with CD and/or UC, but the results were inconsistent. Another SNP that may alter IL-10 production, rs3024505 (C/T) located immediately downstream of the IL10 gene has been recently identified. T allele of rs3024505 was associated with both UC and CD in Western populations, but the studies from East European countries are lacking. Therefore, our aim was to assess the association of rs3024505, rs1800896 and rs1800871 with Serbian IBD patients. To this end, 107 CD and 99 UC patients and 255 healthy controls were genotyped. As a result, T allele of rs3024505 was associated with CD at allelic, genotypic (GT genotype) and haplotypic (GCCT haplotype) level, suggesting potential role of this variant in susceptibility to CD. In contrast, CD patients carrying C allele of rs3024505 had significantly increased risk of anemia and stricturing/penetrating behavior. No association was observed between rs3024505 and UC or SNPs in IL10 promoter region and any form of IBD. In conclusion, rs3024505 SNP flanking the IL10 gene is associated with susceptibility and severity of disease in Serbian CD patients, further validating its role as a potential biomarker in IBD.

Introdution. Tumour necrosis factor alpha (TNF?) has a central role in the host immune response to mycobacterial infection. TNF? blockade may therefore result in reactivation of recent or remotely acquired infection. In reported mycobacterium tuberculosis infections, extra-pulmonary and disseminated tuberculosis (TB) was common, appeared rapidly, and if unrecognized, with fatal outcome. We present a female patient with miliary TB following treatment with infliximab for fistulizing Crohn?s disease. Case Outline. Five years before admission, the patient was diagnosed with Crohn?s disease, with inflammation limited to the terminal ileum and sigmoid colon and has been on azathioprine 100 mg/day for the last 10 months. Three months before admission to the hospital she developed an enterocutaneous fistula for which therapy with infliximab was started in addition to azathioprine therapy. A tuberculin skin test and a chest x-ray were performed prior to the first infusion with normal findings. She presented with a 6-week history of fever, weakness, weight-loss and a 2-week dry cough. Chest x-ray and computed tomography displayed remarkable bilateral hilar and mediastinal lymphadenopathy and uniformly distributed fine nodules throughout both lung fields varying in size from 2 to 3 mm, without any signs of cavitation. Since there were clinical and morphological signs that indicated miliary TB, the treatment with antituberculous therapy was started and six weeks later all of the symptoms completely resolved and the lesions visible on x-ray diminished. Conclusion. The clinical use of TNF-inhibitors is associated with increased risk of developing tuberculosis. Physicians should be aware of the increased risk of reactivation of TB among patients treated with anti-TNF agents and regularly look for usual and unusual symptoms of TB.

It is known that physical activity undoubtedly exhibits positive effects, decreasing the incidence of many chronic diseases. But, at present, physical activity is consider a pre-analytical factor/error related to the sampling process. Namely, different types of physical activity as well as its different intensity may influence a broad array of laboratory variables. The amount of extracellular release and clearance from blood of most of these biomarkers is markedly influenced by the biological characteristics of the molecule(s), level of training, type, intensity and duration of exercise, and time of recovery after training. It is therefore noteworthy to have the anamnestic information about these specific characteristics of physical activity and to understand the "physiologic" effects of exercise on laboratory results and when the threshold to pathological effects has been crossed. There are a lot of research data about the influence of physical activity on laboratory test results, but the accessible results are scattered and inconsistent since variations in type, duration, and intensity of exercise, sample size, and biological, behavioral, and experimental variables are not always adequately controlled. In this study we put an effort to summarize the most often changes in laboratory results that occur as a result of physical activity and to explain these changes in accordance with their biochemical, physiological and metabolic features.

Even though pancreatic cancer is not such a common diagnosis, its treatment is very expensive and it has a great economic impact to the health system. 5-year survival rates after excessive surgical treatment is only 5%, which imposes more careful selection of patients that have to be surgically treated. According to experience from some medical centers all over the world, EUS is considered as a high sensitive diagnostic method for establishing a diagnosis of pancreatic cancer and evaluation of TNM staging. The main purpose of this survey is to present our experience in using of EUS as a diagnostic method in establishing a diagnosis of pancreatic cancer, as well as to evaluate how reliable this method is in preoperative evaluation if tumor could be successfully resected. We examined the group of 63 patients with pancreatic cancer, which were surgically explored after EUS examination. We wanted to compare TNM status before and after the surgical treatment. All patients were examined by Olympus equipment for endoscopic ultrasound with radial probe working with the frequency of 7,5 and 12 MHz at the Department for Endoscopic Ultrasound of the Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia. Evaluation of pancreatic tumor extension to local organs (pancreas, duodenum, choledochus, stomach, colon and large veins) was performed for all patients. All regional lymph nodes were also explored. Due to low penetration ability of the probe working with the frequency of 7.5 MHz, EUS is not a suitable method for evaluation of M stage (figure 8,9). Patients were divided in different groups, specified by TNM status. For 10 patients resection was estimated as a probably successful solution, but only 8 of them was surgically treated. According to this, our estimation was 79.7% accurate, which is in accordance to results obtained from other medical centers all over the world.

Evidences have suggested that flavanol compound (-)-epicatechin is associated with reduced risk of cardiovascular diseases. One of the mechanisms of its cardioprotective effect is vasodilation. However, the exact mechanisms by which (-)-epicatechin causes vasodilation are not yet clearly defined. The aims of the present study were to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human internal mammary artery (HIMA) and to determine the mechanisms underlying its vasorelaxation. Our results showed that (-)-epicatechin induced a concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Among the K(+) channel blockers, 4-aminopyridine (4-AP) and margatoxin, blockers of voltage-gated K(+) (KV) channels, and glibenclamide, a selective ATP-sensitive K(+) (KATP) channels blocker, partly inhibited the (-)-epicatechin-induced relaxation of HIMA, while iberiotoxin, a most selective blocker of large conductance Ca(2+)-activated K(+) channels (BKCa), almost completely inhibited the relaxation. In rings pre-contracted by 80mM K(+), (-)-epicatechin induced partial relaxation of HIMA, whereas in Ca(2+)-free medium, (-)-epicatechin completely relaxed HIMA rings pre-contracted by phenylephrine and caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca(2+)-ATPase inhibitor, slightly antagonized (-)-epicatechin-induced relaxation of HIMA pre-contracted by phenylephrine. These results suggest that (-)-epicatechin induces strong endothelium-independent relaxation of HIMA pre-contracted by phenylephrine whilst 4-AP- and margatoxin-sensitive KV channels, as well as BKCa and KATP channels, located in vascular smooth muscle, mediate this relaxation. In addition, it seems that (-)-epicatechin could inhibit influx of extracellular Ca(2+), interfere with intracellular Ca(2+) release and re-uptake by the sarcoplasmic reticulum.

Background and aim Malnutrition is a common feature of inflammatory bowel disease (IBD). There are numerous methods for the assessment of nutritional status, but the gold standard has not yet been established. The aims of the study were to estimate the prevalence of undernutrition and to evaluate methods for routine nutritional assessment of active IBD patients. Material and methods Twenty-three patients with active Crohn disease, 53 patients with active ulcerative colitis and 30 controls were included in the study. The nutritional status was assessed by extensive anthropometric measurements, percentage of weight loss in the past 1–6 months and biochemical markers of nutrition. Results All investigated nutritional parameters were significantly different in IBD patients compared to control subjects, except MCV, tryglicerides and serum total protein level. Serum albumin level and bodymass index (BMI) were the most predictive parameters of malnutrition. According to different assessment methods the prevalence of undernutrition and severe undernutrition in patients with active IBD were 25.0%–69.7% and 1.3%–31.6%, respectively, while in the control subjects no abnormalities have been detected. There was no statistically significant difference of nutritional parameters between UC and CD patients except lower mid-arm muscle circumference in UC group. Conclusions Malnutrition is common in IBD patients. BMI and serum albumin are simple and convenient methods for the assessment of the nutritional status in IBD patients. Further studies with larger group of patients are necessary to elucidate the prevalence of malnutrition and the most accurate assessment methods in IBD patients.

Villous adenomas are benign epithelial lesions with malignant potential that can occur in any part of the gastrointestinal tract. We present a case of a middle age woman with acromegaly who was investigated for nonspecific gastrointestinal complaints. Ultrasonography and subsequent endosonography diagnosed a large (4.5 cm), hyperechoic, sessile polyp with numerous pedicles. An open cholecystectomy was performed and revealed a villous adenoma with several foci of carcinoma in situ. Detailed investigations showed no other tumors of the gastrointestinal tract. After five years of follow-up, the patient reports no complaints, and the results of laboratory testing and imaging studies are within the normal range.

s / Atherosclerosis 241 (2015) e32ee71 e50 EAS-0759. EPICATECHIN INDUCED VASORELAXATION OF HUMAN INTERNAL MAMMARY ARTERY A. Novakovic , M. Marinko , A. Vranic , G. Jankovic , I. Stojanovic , P. Milojevic , N. Ugresic , V. Kanjuh , Q. Yang , G.W. He . Department of Pharmacology, Faculty of Pharmacy University of Belgrade, Belgrade, Serbia; Department of Surgery, 1) Faculty of Medicine University of Belgrade 2) Institute for Cardiovascular Diseases “Dedinje”, Belgrade, Serbia; Department of Pharmacology, Academy of Sciences and Arts, Belgrade, Serbia; Department of Surgery, The Chinese University of Hong Kong, Hong Kong, Hong Kong China; 5 TEDA International Cardiovascular Hospital, Medical College Nankai University, Tianjin, China Aim: Epicatechin is a flavanol abundantly present in grapes, cocoa and tea. Different biological actions of flavanol-rich foods support their potential cardioprotective effects including vasodilation, as well as reduction of oxidative stress, early event in development of atherosclerosis. Because the exact mechanisms by which epicatechin causes vasodilation are unclear, we aimed to investigate relaxant effect of epicatechin on the isolated human internal mammary artery (HIMA) and its underlying mechanisms. Methods: Discarded segments of HIMA were collected from patients undergoing coronary artery bypass grafting and studied in organ baths. Results: Epicatechin induced a concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Among the K+ channel blockers, 4-aminopyridine and margatoxin, blockers of voltage-gated K+ (KV) channels, and glibenclamide, a selective ATP-sensitive K+ (KATP) channels blocker, partly inhibited the epicatechin-induced relaxation of HIMA, while iberiotoxin, a most selective blocker of large conductance Ca2+-activated K+ channels (BKCa), almost completely inhibited the relaxation. In rings pre-contracted by 80 mM K+, epicatechin induced partial relaxation of HIMA, whereas in Ca2+-free medium, epicatechin completely relaxed HIMA rings pre-contracted by phenylephrine and caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca2+-ATPase inhibitor, slightly antagonized epicatechin-induced relaxation of HIMA pre-contracted by phenylephrine. Conclusions: These results suggest that epicatechin induces strong endothelium-independent relaxation of HIMA pre-contracted by phenylephrinewhilst 4-aminopyridineandmargatoxin-sensitive KV channels, as well as BKCa and KATP channels, located in vascular smooth muscle, mediate this relaxation. In addition, it seems that epicatechin could inhibit influx of extracellular Ca2+, interfere with intracellular Ca2+ release and reuptake by the sarcoplasmic reticulum. CV risk factors and atherosclerosis II EAS-0052. INFANT BIRTH WEIGHT AND RISK FACTORS FOR ADULT CARDIOVASCULAR DISEASE INCLUDING BODY MASS INDEX IN THE LIFEWAYS CROSS-GENERATION COHORT STUDY OF A THOUSAND FAMILIES S. McKey, M. Heinen, R. Segurado, J.O.H.N. Mehegan, C. Murrin, C. Kelleher. School of Public Health Physiotherapy and Population Science, University College Dublin, Dublin, Ireland Background: Infant birth-weight predicts risk of adult chronic disease and more recently studies have reported on cross-generation transmission of risk patterns. The Lifeways study is highly novel, with information on three generations of the same families. Aim: To examine whether adults' birth-weights were associated with measures of own health status, or social position and to relate these also to infant birth-weights (BW) of index child or grandchild. Methods: Participants were 1083 children and 934 adult cohort members, mothers, fathers and grandparents, recruited in 2001, followed prospectively until 2014. At baseline adults reported own birth weight (RBW) by questionnaire. Child's birth-weight was from hospital records. At descriptive uni-variate level, categorical chi2 and Pearson's correlations were performed. A multi-level mixed effects linear regression model with adults' body mass index as the outcome variable was also undertaken. Results: Male adults' RBW were significantly higher than females' (p1⁄40.001). There was a u-shaped association with education in that those adults with highest education were least likely to be in either the highest or lowest tertile for RBW (p1⁄40.004). Child's BW was correlated positively with that of mother for both sexes (r 1⁄4 0.168, p1⁄40.001). Paternal grandfather's RBW was inversely associated with child's BW (r1⁄4-0.424, p1⁄40.039). In the multi-level model, adults' BMI was positively associated with age (p1⁄40.000), index child's BW (p1⁄40.001), educational status (p1⁄40.001), group (0.011) but not RBW, adjusting for family ID. Conclusion: Cross-generational associations for birth-weight and BMI are confirmed in the Lifeways cohort, consistent with the developmental origins of disease hypothesis. EAS-0100. RELATIONS BETWEEN RETINAL ARTERIOLES ANATOMY AND LARGE ARTERY GEOMTRY AND FUNCTION AND PERIPHERAL RESISTANCE IN HYPERTENSIVES D. Rosenbaum, N. Kachenoura , E. Koch , M. Paques , P. Cluzel , E. Brucket , A. Redheuil , X. Girerd . Cardiovascular prevention, GH Piti eSalpetri ere, Paris, France; 2 laboratoire d'imagerie biom edicale, INSERM U1166, Paris, France; CIC des 15/20, Institut de la vision, Paris, France; Cardiovascular imaging department, GH Piti e Salpetri ere, Paris, France; 5 cardiovascular prevention unit, GH Piti e Salpetri ere, Paris, France Background: Microvascular remodeling and large artery stiffness are key determinants of blood pressure (BP) yet they are difficult to study noninvasively in humans. Our objective was to study relationships between retinal arterioles anatomy and total peripheral resistance (TPR) as well as with large artery geometry and function in hypertension. Methods and results: Demographics, ambulatory home and central BP were assessed in 80 subjects (age 52±13 years; 53% male): 23 normotensives, 28 treated and controlled hypertensives and 29 treated and uncontrolled hypertensives. Retinal arteriolar wall-to-lumen ratio (WLR) was assessed non-invasively using an Adaptive Optic camera. Carotido-femoral pulse wave velocity (Cf-PWV) was assessed along with cardiovascular MRI ascending aorta distensibility (AAD), geometry and ultrasound carotid intima media thickness (IMT). TPR was calculated using central BP and CMR-derived aortic flow. WLR, IMT and TPR were significantly higher and AAD lower in hypertensives, compared to normotensives. In univariate analysis, WLR correlated positively with central BP (p

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