Inflammatory Bowel Disease Therapies and Acute Liver Injury.

Drug-induced liver disease (DILI) represents one of the main problems in the therapeutic field. There are several non-modifiable risk factors, such as age and sex, and all drugs can cause hepatotoxicity of varying degrees, including those for the treatment of inflammatory bowel diseases (IBD). The aim of this review is to illustrate the adverse effects on the liver of the various drugs used in the treatment of IBD, highlighting which drugs are safest to use based on current knowledge. The mechanism by which drugs cause hepatotoxicity is not fully understood. A possible cause is represented by the formation of toxic metabolites, which in some patients may be increased due to alterations in the enzymatic apparatus involved in drug metabolism. Various studies have shown that the drugs that can most frequently cause hepatotoxicity are immunosuppressants, while mesalazine and biological drugs are, for the most part, less associated with such complications. Therefore, it is possible to assume that in the future, biological therapies could become the first line for the treatment of IBD.

Composition of gut microbiota and its correlations with neurological, intestinal, cardiovascular and metabolic diseases.

The intestinal microbiota is a microenvironment that has been the subject of studies for several decades. Over time, it has been reconsidered as a possible cofactor of multiple acute and chronic human diseases. In fact, alterations of the intestinal bacterial flora have been found in various neurological diseases. There are three modes of interaction between the intestinal microbiota and the gut-brain-axis: chemical signals, neural pathways and immune system. Even at the gastrointestinal level, the gut microbiota plays certainly an important role in the etiopathogenesis of chronic intestinal inflammatory diseases but also in irritable bowel syndrome. An important correlation has also been demonstrated with non-alcoholic fatty liver disease, as well as in other metabolic, cardiovascular and oncological diseases. Bacteria, viruses, fungi and various microorganisms that normally reside in our intestines can also be called into question as protective factors against these diseases. All this evidence leads researchers to consider the gut microbiota as a key element in the determination of aforementioned diseases. Therefore, it would be foreseeable in the future to associate the use of probiotics with the therapies used in the treatment of all these diseases. In this review we have condensed the main current knowledge regarding the link between the most frequent diseases and the gut microbiota.

Natural Compounds as Integrative Therapy for Liver Protection against Inflammatory and Carcinogenic Mechanisms: From Induction to Molecular Biology Advancement.

The liver is exposed to several harmful substances that bear the potential to cause excessive liver damage ranging from hepatitis and non-alcoholic fatty liver disease to extreme cases of liver cirrhosis and hepatocellular carcinoma. Liver ailments have been effectively treated from very old times with Chinese medicinal herbal formulations and later also applied by controlled trials in Japan. However, these traditional practices have been hardly well characterized in the past till in the last decades when more qualified studies have been carried out. Modern advances have given rise to specific molecular targets which are specifically good candidates for affecting the intricate mechanisms that play a role at the molecular level. These therapeutic regimens that mainly affect the progression of the disease by inhibiting the gene expression levels or by blocking essential molecular pathways or releasing cytokines may prove to play a vital role in minimizing the tissue damage. This review, therefore, tries to throw light upon the variation in the therapies for the treatment of benign and malignant liver disease from ancient times to the current date. Nonetheless, clinical research exploring the effectiveness of herbal medicines in the treatment of benign chronic liver diseases as well as prevention and treatment of HCC is still warranted.

Non-alcoholic fatty liver disease: correlation with hyperuricemia in a European Mediterranean population.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are two pathologies that intersect each other. It was found that there is an association between MetS/NAFLD and hyperuricemia. The aim of our study was to demonstrate this association in a European Mediterranean population. METHODS: We compared 236 patients with NAFLD to 218 patients without NAFLD. We assessed laboratory metabolic parameters (serum uric acid - SUA, fasting glucose, triglycerides, total cholesterol, etc.) and the presence or absence of MetS in a retrospective, cross-sectional, case-control manner. RESULTS: Analysis of the two main variables in study showed a moderate direct correlation (p< 0.01; Pearson coefficient 0.443) between SUA and NAFLD. Evaluation for SUA quartiles showed a decreased risk of NAFLD for the first and second quartiles (OR Q1 = 0.20; OR Q2 = 0.59), but increased for the third and fourth quartiles (OR Q3 = 2.22; OR Q4 = 6.97). In females, the risk of NAFLD was less compared to males for the first three quartiles of SUA, but it was more than double for the fourth quartile (OR Q1 0.21 vs 0.16; OR Q2 0.82 vs 0.45; OR Q3 2.50 vs 2.26; OR Q4 4.50 vs 9.83). In the NAFLD group, hyperuricemia was significantly correlated with sex, obesity, hypertension, and with the number of components of the MetS. In the Control group, SUA directly correlated with age, diabetes, and ALT, but not with obesity. CONCLUSION: We have found a significant correlation between NAFLD and hyperuricemia. The higher SUA levels accompanied the risk of NAFLD.

Triglycerides to high-density lipoprotein cholesterol ratio for diagnosing nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic Fatty Liver Disease (NAFLD) is a widespread disease in the western world. It can develop into more serious pathological conditions (i.e. liver cirrhosis). Therefore, it is important to diagnose it in order to prevent this evolution. For diagnosis it is possible to use both imaging methods and biomarkers, such as the Triglycerides To High-Density Lipoprotein Cholesterol Ratio (TG/HDL-C). Aim of our study is to determine whether TG/HDL-C ratio is significantly associated with NAFLD and Metabolic Syndrome (MetS). METHODS: We recruited 231 patients, 131 with and 100 without NAFLD. The Body Mass Index had been calculated and different laboratory parameters had been obtained. TG/HDL-C ratio was calculated for each. RESULTS: In our sample HDL-C was not significantly reduced in NAFLD group (P=0.49), but higher TG and TG/HDL-C ratio were significantly associated with NAFLD: in both P<0.001. According to receiver operating characteristic curve, the best cut-off of TG/HDL-C in NAFLD population was 1.64 (area under the curve [AUC] 0.675 [95% CI 0.604-0.746], P<0.001). TG/HDL-C higher ratio was significantly associated with MetS (P<0.001). The best cut-off of TG/HDL-C in patients with MetS was 2.48 (AUC 0.871 [95% CI 0.808-0.935], P<0.001). CONCLUSIONS: We demonstrated that higher TG/HDL-C ratio is associated with NAFLD and MetS. Though nowadays TG/HDL-C ratio is not a criteria for NAFLD diagnosis, we believe that in the future it could be used as a reliable non-invasive marker in routine diagnostics of NAFLD.

FIB-4 and APRI scores for predicting severe liver fibrosis in chronic hepatitis HCV patients: a monocentric retrospective study.

AIM OF THE STUDY: Hepatitis C virus (HCV) can cause a chronic liver infection which could then develop into fibrosis, cirrhosis, and hepatocellular carcinoma. Today the diagnosis of liver fibrosis also includes the use of biomarkers. The purpose of our study was to determine the ability of the fibrosis index based on four factors (FIB-4) and aspartate aminotransferase-to-platelet ratio (APRI) to predict the severity of liver fibrosis or cirrhosis. MATERIAL AND METHODS: Medical records of 106 patients with HCV-related liver fibrosis were analyzed. All patients underwent clinical examination, blood tests (complete blood count, total bilirubin, etc.) and transient elastography. FIB-4 and APRI were calculated for each patient. RESULTS: Twenty-six patients (24.52%) had F4 fibrosis, 80 patients (75.48%) had non-F4 fibrosis (F0-F3). There was a statistically significant difference (p < 0.05) between non-F4 fibrosis patients and F4 fibrosis patients in many parameters, including APRI (F4 fibrosis patients had higher values: 2.06 ±3.22 compared to 0.68 ±0.76 of the non-F4 group; p = 0.044) and FIB-4 (F4 fibrosis patients had higher values: 4.84 ±4.14 compared to 2.29 ±2.90 of the non-F4 group; p = 0.006). Receiver operating characteristic (ROC) curve analysis for APRI and FIB-4 revealed that the area under the curve (AUC) of FIB-4 was 0.855 (CI: 0.813-0.936), while the APRI score had an AUC of 0.767 (CI: 0.79-0.932). CONCLUSIONS: In this study, patients with severe fibrosis or cirrhosis were found to have a higher FIB-4 value than APRI in the context of chronic hepatitis C.

Lactose intolerance: An update on its pathogenesis, diagnosis, and treatment.

Lactose intolerance has a high prevalence worldwide, ranging between 57% and 65%. It is caused by a reduction or loss of the activity of the intestinal enzyme lactase-phlorizin hydrolase, responsible for the digestion of lactose. This alteration determines an increased osmotic load in the small intestine and the fermentation of lactose by the bacterial flora, which leads to a high production of short-chain fatty acids and gas. This is followed by the onset of abdominal pain, diarrhea, and flatulence. In addition to these problems, it was found that subjects with lactose intolerance have an increased risk of developing various extra-intestinal diseases, including cancers. The diagnosis is essential to undertake an adequate treatment and, for this purpose, different methods have been tested. These include genetic test, hydrogen breath test (HBT), quick lactase test, and lactose tolerance test. HBT is the most used method because it is non-invasive, inexpensive, and highly sensitive and specific, as well as easy to perform. In clinical practice, the other methods are mainly used as HBT integration tests. There are also many therapeutic options. An appropriate intervention concerns the dietetic style, such as the consumption of lactose-free foods, but with nutritional characteristics comparable to dairy products. Other valid choices are represented by the use of exogenous enzymes, probiotics, prebiotics, the selection of milk containing specific types of beta-caseins. This review is intended to illustrate the diagnostic methods currently available and the possible therapeutic options for lactose intolerance.

Beyond Physical Exercise: The Role of Nutrition, Gut Microbiota and Nutraceutical Supplementation in Reducing Age-Related Sarcopenia.

Sarcopenia is a commonly prevalent geriatric condition mainly characterized by progressive loss of the skeletal muscle mass that results in noticeably reduced muscle strength and quality. Most of the geriatric population above 60 years of age are overweight, leading to the accumulation of fat in the muscles resulting in abated muscle function. The increased loss of muscle mass is associated with high rates of disability, poor motility, frailty and mortality. The excessive degeneration of muscles is now also being observed in middle-aged people. Therefore, geriatrics has recently started shifting towards the identification of early stages of the disability in order to expand the life span of the patient and reduce physical dependence. Recent findings have indicated that patients with increased physical activity are also affected by sarcopenia, therefore indicating the role of nutritional supplements to enhance muscle health which in turn helps to counteract sarcopenia. Various interventions with physical training have not provided substantial improvements to this disorder, thereby highlighting the crucial role of nutritional supplementation in enhancing muscle mass and strength. Nutritional supplementation has not only been shown to enhance the positive effects of physical interventions but also have a profound impact on the gut microbiome that has come forward as a key regulator of muscle mass and function. This brief review throws light upon the efficiency of nutrients and nutraceutical supplementation by highlighting their ancillary effects in physical interventions as well as improving the gut microbiome status in sarcopenic adults, thereby giving rise to a multimodal intervention for the treatment of sarcopenia.

Irritable bowel syndrome and lactose intolerance: the importance of differential diagnosis. A monocentric study.

BACKGROUND: Nowadays irritable bowel syndrome (IBS) and lactose intolerance (LI) are two very frequent diseases. IBS is a functional disorder, while LI is caused by the inability to digest lactose. LI is often incorrectly diagnosed as IBS. The aim of our study is to identify LI patients among IBS patients, so as to set up a correct therapy. METHODS: We enrolled 259 patients with IBS and we compared them to a control group of 108 patients. All patients underwent H2 Breath-Test (HBT) and two questionnaires regarding the symptoms associated with IBS and LI were administered to the intolerant subjects and one questionnaire to IBS patients with no LI. RESULTS: At the HBT, 79.9% (N.=207) of patients with IBS were positive, while in the control group were positive 25.0% (N.=27) of subjects (P<0.001). The questionnaires showed, after a month of therapy, a marked improvement in LI symptoms subjects. In addition, there was also a prevalence of more severe symptoms among subjects with IBS and LI than those with IBS and no LI. CONCLUSIONS: We can affirm that most patients with initial diagnosis of IBS are, instead, lactose intolerant. This diagnosis allows us to undertake an adequate therapy so as to improve symptoms and quality of life. Therefore it is important to include LI in the pathologies with which IBS enters into differential diagnosis.

Platelet to lymphocyte ratio as a predictive biomarker of liver fibrosis (on elastography) in patients with hepatitis C virus (HCV)-related liver disease.

BACKGROUND: Liver fibrosis is a frequent complication of chronic hepatitis C virus (HCV) infection. Its evaluation is very important for the prognosis of these patients. The aim of this study was to evaluate the possibility of exploiting the platelet to lymphocyte ratio and the neutrophil to lymphocyte ratio as non-invasive predictive markers of liver fibrosis. METHODS: We recruited 120 patients with chronic HCV infection. They were subjected to various clinical investigations to assess the severity of fibrosis. Transient elastography and some serological tests were performed, and the platelet to lymphocyte ratio and the neutrophil to lymphocyte ratio were estimated. RESULTS: Sixty-four patients had F4 fibrosis (defined by elastography) and their platelet to lymphocyte ratio (69.92 ± 26.47) was lower than in patients with non-F4 fibrosis (95.19 ± 48.15) (p = 0.001). The neutrophil to lymphocyte ratio was also estimated, but the difference between the 2 groups of patients was not significant statistically (p = 0.07). CONCLUSION: The platelet to lymphocyte ratio can be used as a predictive biomarker of liver fibrosis, unlike the neutrophil to lymphocyte ratio which is not predictive of this HCV-related chronic hepatitis complication. More studies are needed to validate this hypothesis.

Benefits of aged garlic extract in modulating toxicity biomarkers against p-dimethylaminoazobenzene and phenobarbital induced liver damage in Rattus norvegicus.

Garlic (Allium sativum L.), a popular spice, has been used for decades in treating several medical conditions. Although Allicin, an active ingredient of garlic has been extensively studied on carcinogen-induced hepatotoxicity and oxidative stress in rats (Rattus norvegicus), no systematic study on the beneficial effects of generic aged garlic and specific aged garlic extract-Kyolic has been done. The present study involves rats fed chronically with two liver carcinogens, p-dimethylaminoazobenzene and phenobarbital, to produce hepatotoxicity. The aged garlic extract was characterized by UV-spectra, FTIR, HPLC and GC-MS. Biochemical and pathophysiological tests were performed by keeping suitable controls at four fixation intervals, namely, 30, 60, 90, and 120 days, utilizing several widely accepted toxicity biomarkers. Compared to the controls, remarkable elevation in the activities of lactate dehydrogenase, gamma glutamyl transferase and decline in catalase and glucose-6-phosphate dehydrogenase were observed in the carcinogen fed rats. Daily administration of aged garlic extract, could favorably modulate the elevated levels of various toxicity biomarkers including serum triglyceride, creatinine, urea, bilirubin, blood urea nitrogen except total cholesterol. It also altered the levels of blood glucose, HDL-cholesterol, albumin, AST, ALT, and hemoglobin contents in carcinogen intoxicated rats, indicating its protective potential against hepatotoxicity and oxidative stress in the experimental rats. Down-regulation of Bcl-2 and p53 proteins caused cell cycle arrest and apoptosis in garlic fed group. Kyolic exhibited additional benefits by arresting cell viability of cancer cells. This study would thus validate the use of aged garlic extract in the treatment of diseases causing liver toxicity including hepatocarcinoma.

Benign pancreatic hyperenzymemia-Gullo's syndrome: focus on this clinical challenge. A monocentric retrospective study.

BACKGROUND: An abnormal and chronic rise of pancreatic enzymes in the blood is most often due to pancreatic diseases, primarily inflammatory or neoplastic, or to numerous extra-pancreatic pathologies. Benign chronic pancreatic hyperenzymemia was described for the first time - as a separate nosological entity - in 1996 by Lucio Gullo et al. They demonstrated the existence of a benign chronic pancreatic hyperenzymemia in asymptomatic subjects and without clinical implications; however, a follow-up of at least 1-2 years is necessary during which no specific symptomatology or morpho-functional impairment of the pancreas should occur, also evaluated through the aid of instrumental diagnostic investigations such as ultrasonography (US), computed tomography (CT) or magnetic resonance cholangio pancreatography (MRCP). METHODS: This study was performed with the analysis of a group of 43 subjects arrived at the observation of the Gastroenterology Team of Policlinico Hospital G. Rodolico in Catania-Italy which presented a chronic pancreatic hyperenzymemia, in order to establish the actual benignity of this condition over time. RESULTS: During the follow-up, pancreatic alterations and hyperenzymemia were found in 10 patients, while hyperenzymemia was not associated with pancreatic modification in 33 patients. CONCLUSIONS: Because of this enzymatic elevation - often conspicuous and lasting - the patient is often particularly anxious. For the same reason, the patient frequently undergoes very expensive laboratory and instrumental diagnostic methods. Good knowledge of the syndrome makes it possible to manage the event more rationally, also to reduce management costs to a minimum.

Effect of VBC-1814/7J, a poly-phytocompound, on a non-infectious model of pharyngitis.

Pharyngitis presents as an inflammation of the oropharynx, and clinical examination often shows evidence of nasopharyngitis. In numerous cases the condition occurs as a self-limiting illness of non-infectious aetiology, whose clinical management remains a matter for debate given the inappropriateness of antibiotics, the reported worsening following steroid use and the recent discouragement of the use of Chinese herbal medicine. The aim of the present study was thus to test VBC-1814/7J, a poly-phytocompound with known anti-inflammatory and immune-response enhancing properties, in an experimental model of non-infectious pharyngitis. Experimental non-infectious pharyngitis was induced by applying a pyridine solution to the surface of the pharyngeal mucosa in rats that were either normally fed (group A) or fed VBC-1814/7J three days prior to and three days subsequent to the induction of pharyngitis (group B). Healthy rats treated with topical saline were used as a control (group C). At time-points of 0, one hour, one day and three days sacrifices were carried out and microscopic examination, Evans blue (EB) dye extravasation and tissue concentrations of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and mRNA of α- and ß-defensins were studied. As compared with group C, group A showed significant microscopic damage, EB extravasation, and increases in the levels of TNF-α and IL-6, as well as in the mRNA of three defensins (P<0.001) on the third day of observation. VBC-1814/7J significantly mitigated these microscopic and inflammatory markers while allowing a prompter and wider defensin reaction (P<0.05 vs. group A). These data suggest that VBC-1814/7J, as demonstrated in earlier studies, has the potential to address non-infectious pharyngitis in clinical practice.

A 2-year Double-Blind RCT Follow-up Study with Fermented Papaya Preparation (FPP) Modulating Key Markers in Middle-Age Subjects with Clustered Neurodegenerative Disease-Risk Factors.

In recent years a number of studies have reported the significant relationship between metabolic syndrome and neurodegenerative disease. There is accumulating evidence that the interplay of combined genetic and environmental risk factors (from diet to life style to pollutants) to intrinsic age-related oxi-inflammatory changes may be advocated for to explain the pandemic of neurodegenerative diseases. In recent years a specific Fermented Papaya Preparation (FPP) has been shown to significantly affect a number of redox signalling abnormalities in a variety of chronic diseases and as well in aging mechanisms either on experimental and on clinical ground. The aim of the present study was to evaluate FPP use in impending metabolic disease patients with potentially neurodegenerative disease clustered risk factors. The study population consisted of 90 patients aged 45-65 years old, with impending metabolic syndrome and previously selected as to be ApoE4 genotype negative. By applying a RCT, double-blind method, one group received FPP 4.5 g twice a day (the most common dosage utilized in prior clinical studies) while the other received an oral antioxidant cocktail (trans-resveratrol, selenium, vitamin E, vitamin C). Then, after 21 month treatment period, a selected heavy metal chelator was added at the dosage of 3 g/nocte for the final 3 months study treatment. The parameters tested were: routine tests oxidized LDL-cholesterol, anti-oxidised LDL, Cyclophilin-A (CyPA), plasminogen activator inhibitor-1 and CyPA gene expression. From this study it would appear that FPP, unlike the control antioxidant, significantly decreased oxidized-LDL and near normalizing the anti-Ox-LDL/Ox-LDL ratio (p<0.001) although unaffecting the lipid profile per sè. Moreover, only FPP decreased cyclophilin-A plasma level and plasminogen activator-inhibitor (p<0.01) together with downregulating cyclophilin-A gene expression (p<0.01). Insulin resistance was only mildly improved. Heavy metals gut clearance proved to be effectively enhanced by the chelator (p<0.01) and this was not affected by any of the nutraceuticals, nor it added any further benefit to the biological action of FPP.

Exploring the metabolic syndrome: Nonalcoholic fatty pancreas disease.

After the first description of fatty pancreas in 1933, the effects of pancreatic steatosis have been poorly investigated, compared with that of the liver. However, the interest of research is increasing. Fat accumulation, associated with obesity and the metabolic syndrome (MetS), has been defined as "fatty infiltration" or "nonalcoholic fatty pancreas disease" (NAFPD). The term "fatty replacement" describes a distinct phenomenon characterized by death of acinar cells and replacement by adipose tissue. Risk factors for developing NAFPD include obesity, increasing age, male sex, hypertension, dyslipidemia, alcohol and hyperferritinemia. Increasing evidence support the role of pancreatic fat in the development of type 2 diabetes mellitus, MetS, atherosclerosis, severe acute pancreatitis and even pancreatic cancer. Evidence exists that fatty pancreas could be used as the initial indicator of "ectopic fat deposition", which is a key element of nonalcoholic fatty liver disease and/or MetS. Moreover, in patients with fatty pancreas, pancreaticoduodenectomy is associated with an increased risk of intraoperative blood loss and post-operative pancreatic fistula.

Beneficial effect of refined red palm oil on lipid peroxidation and monocyte tissue factor in HCV-related liver disease: a randomized controlled study.

BACKGROUND: A large amount of endotoxin can be detected in the peripheral venous blood of patients with liver cirrhosis, contributing to the pathogenesis of hepatotoxicity because of its role in oxidative stress. The present study aimed to test the effect of the supplementation with red palm oil (RPO), which is a natural oil obtained from oil palm fruit (Elaeis guineensis) rich in natural fat-soluble tocopherols, tocotrienols and carotenoids, on lipid peroxidation and endotoxemia with plasma endotoxin-inactivating capacity, proinflammatory cytokines profile, and monocyte tissue factor in patients with chronic liver disease. METHODS: The study group consisted of sixty patients (34 males and 26 females; mean age 62 years, range 54-75) with Child A/B, genotype 1 HCV-related cirrhosis without a history of ethanol consumption, randomly enrolled into an 8-week oral daily treatment with either vitamin E or RPO. All patients had undergone an upper gastrointestinal endoscopy 8 months before, and 13 out of them showed esophageal varices. RESULTS: Both treatments significantly decreased erythrocyte malondialdehyde and urinary isoprostane output, only RPO significantly affected macrophage-colony stimulating factor and monocyte tissue factor. Liver ultrasound imaging did not show any change. CONCLUSIONS: RPO beneficially modulates oxidative stress and, not least, downregulates macrophage/monocyte inflammatory parameters. RPO can be safely advised as a valuable nutritional implementation tool in the management of chronic liver diseases.

PROBIOTIC APPROACHES FOR TARGETING INFLAMMATORY BOWEL DISEASE: AN UPDATE ON ADVANCES AND OPPORTUNITIES IN MANAGING THE DISEASE.

Various commensal enteric and pathogenic bacteria may be involved in the pathogenesis of inflammatory bowel diseases (IBDs), a chronic condition with a pathogenic background that involves both immunogenetic and environmental factors. IBDs comprising of Crohn's disease, and ulcerative colitis, and pauchitis are chronic inflammatory conditions, and known for causing disturbed homeostatic balance among the intestinal immune compartment, gut epithelium and microbiome. An increasing trend of IBDs in incidence, prevalence, and severity has been reported during recent years. Probiotic strains have been reported to manage the IBDs and related pathologies, and hence are current hot topics of research for their potential to manage metabolic diseases as well as various immunopathologies. However, the probiotics industry will need to undergo a transformation, with increased focus on stringent manufacturing guidelines and high-quality clinical trials. This article reviews the present state of art of role of probiotic bacteria in reducing inflammation and strengthening the host immune system with reference to the management of IBDs. We infer that t healthcare will move beyond its prevailing focus on human physiology, and embrace the superorganism as a paradigm to understand and ameliorate IBDs.

In vitro protective effect of Celergen, a bioactive marine compound, on interleukin-6-related invasiveness of pancreatic cancer.

The purpose of this study was to assess the effect of Celergen, a marine nutraceutical, against tumor cell invasion in human pancreatic cancer cell line (PSN-I). High invasive clone (HI) and low invasive clone (LI) were established from wild type PSN-l cell line after a repeated invasion assay test. The invasive ability of HI cells and the level of IL-6 in the conditioned medium of HI cells was significantly higher than that one of LI cells but both these parameters were significantly reduced by the addition of Celergen (p<0.01). Exogenous IL-6 administration induced a dose dependent enhancement of invasive ability in both cell populations. Moreover, IL-6 receptor expression was detected in 72% of HI cells whereas this occurred only in 37% of LI cells. When co-cultured with Celergen this parameter was significantly downregulated in both cellular subsets (p<0.05). The addition of conditioned medium derived from HI cells (HCM) and LI cells(LCM) enhanced the invasive ability in both cell populations without affecting cell proliferation. The effect of HCM on the invasive ability of HI cells was partially inhibited by the addition of Celergen (p<0.01). In summary, overexpression of IL-6 and its receptor may be one relevant factor contributing to the highly invasive characteristic of the pancreatic cancer cell line we used while a significantly beneficial modulation was obtained by applying this novel marine nutraceutical. This advices to further explore the possibility of marine compounds regulation of IL-6 ligand/receptor and other possible invasive factor interaction in the therapy of this malignancy while further studies are awaited in this setting.

Nonalcoholic fatty liver disease increases risk for gastroesophageal reflux symptoms.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is now recognized as a leading cause of liver dysfunction. Gastroesophageal reflux disease (GERD) is a common disorder causing symptoms that often impair patients' quality of life. In recent years, the prevalence of both these diseases has increased, partially overlapping the rise of metabolic disorders. AIMS: We investigated whether a relation does exist between NAFLD and GERD symptoms. METHODS: Cross-sectional study among 206 outpatients diagnosed with NAFLD and 183 controls. We collected clinical and laboratory data, assessed severity and frequency of GERD symptoms and the esophageal endoscopic pattern. RESULTS: The prevalence of GERD symptoms was higher in NAFLD patients than controls (61.2 vs. 27.9%, p < 0.001). We found a positive association between NAFLD and the experiencing of heartburn, regurgitation and belching. GERD symptoms were related to body mass index (BMI) and metabolic syndrome (MetS); a strong association persisted after adjustment for all the covariates (adjusted OR 3.49, 95 CI% 2.24-5.44, p < 0.001). CONCLUSIONS: Our data show that the prevalence of GERD typical symptoms is higher in patients with NAFLD. GERD was associated with higher BMI and MetS, but not with age and diabetes type 2. NAFLD remained strongly associated with GERD, independently of a coexisting MetS status. Consistent with these findings, MetS can be considered a shared background, but cannot completely explain this correlation. We suggest NAFLD as an independent risk factor for GERD symptoms.