ARTICLE Download: 38| View: 148| Comments: 0 | doi:10.20944/preprints201910.0136.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: apoptosis; cardiotrophin-1; colon; inflammation
Online: 12 October 2019 (03:38:00 CEST)
Ulcerative colitis (UC) is a relatively frequent, chronic disease that impacts significantly the patient’s quality of life. Although many therapeutic options are available, additional approaches are needed because many patients either do not respond to current therapies or show significant side effects. Cardiotrophin-1 (CT-1) is a cytokine with potent cytoprotective, anti-inflammatory, and antiapoptotic properties. The purpose of this study was to assess if the administration of CT-1 could reduce colon damage in mice with experimental UC. UC was induced with 5% dextran sulfate sodium (DSS) in the drinking water. Some mice received i.v. dose of CT-1 (200 µg/kg) 2 hours before and 2 and 4 days after DSS administration. Animals were followed during 7 days after DSS. The severity of UC was measured by standard scores. Colon damage was assessed by histology and immunohistochemistry. Inflammatory mediators were measured by Western blot and PCR. CT-1 administration to DSS-treated mice ameliorated both the clinical course (disease activity index), histological damage, inflammation (colon expression of TNF-α, IL-17, IL-10, INF-γ, and iNOS), and apoptosis. Our results suggest that CT-1 administration before UC induction improves the clinical course, tissue damage and inflammation degree in DSS-induced UC in mice.
Mon, 7 October 2019
CASE REPORT Download: 11| View: 68| Comments: 0
Subject: Medicine & Pharmacology, Gastroenterology Keywords: diarrhea; wood creosote; Seirogan; retrospective study; capsule
Online: 7 October 2019 (10:52:58 CEST)
Seirogan, a wood creosote, is a nonprescription drug used to treat diarrhea. However, reports of its clinical use are rare. Here, we report on the efficacy of wood creosote (3 capsules daily) for the alleviation of diarrheal symptoms in 148 patients from 10 clinics in Japan. The wood creosote capsules were classified as remarkably effective (44 patients), effective (71 patients), and partially effective (13 patients) based on the degree of alleviation of diarrheal symptoms that were induced by a variety of causes. The antidiarrheal efficacy of the capsules did not differ between males and females, and young patients (21–30 years) showed greater improvement in diarrheal symptoms than did old patients (> 61 years). Although this report is based on the re-evaluation of old data that had been preserved by our company, the effectiveness and range of symptoms that were treatable with wood creosote has likely remained unchanged. To the best of our knowledge, this is the first public report on the clinical effectiveness of wood creosote capsules for the treatment of a wide range of diarrheal symptoms.
Fri, 20 September 2019
ARTICLE Download: 30| View: 187| Comments: 0
Subject: Medicine & Pharmacology, Gastroenterology Keywords: quality of life; celiac disease; parents; caregivers
Online: 20 September 2019 (19:04:08 CEST)
Celiac disease (CD) is an autoimmune disorder triggered by the ingestion of gluten and affects approximately 1% of the global population. Currently, the only treatment available is lifelong strict adherence to a gluten-free diet (GFD). Chronic diseases such as CD affect patients and their family members’ quality of life (QoL); particularly parents and caregivers who play an essential role in the child’s care and treatment. A higher level of psychological distress has been found in the parents of children with chronic ailments due to limited control over the child’s daily activities and the child’s illness. In this context, the validation of a specific questionnaire of QoL is a valuable tool to evaluate the difficulties faced by parents or caregivers of children with this chronic illness. A specific questionnaire for this population can elucidate the reasons for stress in their daily lives as well as the physical, mental, emotional, and social impact caused by CD. Therefore, this study aimed to develop and validate a specific questionnaire to evaluate the QoL of parents and caregivers of children and adolescents with CD. The study was developed in six steps: (i) development of the CD parent/caregiver QoL questionnaire (CDPC-QoL); (ii) subjective evaluation; (iii) validation of the questionnaire by the Delphi method; (iv) evaluation of the internal consistency and reproducibility of the CDPC-QoL; (v) application of the questionnaire to Brazilian CD parents or caregivers; and (vi) statistical analysis. Overall results showed that a higher family income resulted in a higher score of the worries domain. In addition, having another illness besides CD decreased the QoL (except in the worries domain). The other variables studied did not present a statistically significant impact on the QoL, which was shown to be low in all aspects. Knowledge of the QoL is important to help implement effective strategies to improve celiac patients’ quality of life and reduce their physical, emotional, and social burden.
Wed, 18 September 2019
ARTICLE Download: 24| View: 231| Comments: 1 | doi:10.20944/preprints201909.0214.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: endoscopic retrograde cholangiopancreatography; elderly; adverse event; difficult cannulation
Online: 18 September 2019 (17:54:04 CEST)
Endoscopic retrograde cholangiopancreatography (ERCP) is a routinely used therapeutic procedure for the biliary and pancreatic diseases. Population aging may increase the typical indications of ERCP and come with more complexity and difficulties, especially in cannulation. This study aimed to evaluate the incidence, causes, and management of difficult biliary cannulation during ERCP in super-aged patients and the role of difficult cannulation as a risk factor for adverse events. A total of 614 patients, underwent ERCP, were prospectively studied as a cohort and divided into two groups based on their age. There were 146 patients aged 80 years or older in group A and 468 patients aged less than 80 years in group B. The primary outcome measures were the difficulty grade of papilla cannulation, clinical outcomes, and ERCP-related complications in the two groups. The adverse events were analyzed using logistic regression for patient age, co-morbidities, indications, and cannulation difficulty grade variables. There was no difference in the incidence of difficult cannulation between the two groups (32.9% vs. 34.4%, p=0.765) though, as expected, super-aged Group A had a higher prevalence of periampullary diverticulum (29.5% vs. 16.7%, p=0.001). The technical cannulation success rate was (96.6% vs. 96.8%, p= 0.54). All used cannulation techniques in the elderly group were efficient and safe. Logistic regression showed that age ≥80 was not associated with increased adverse events; however, difficult cannulation (adjusted odds ratio [AOR]=3.478; 95% confidence interval [CI]=1.877, 6.442; p<0.001) and CCI ≥2 (AOR=1.824; 95% CI=0.993, 3.349; p=0.045) were more likely to have adverse events. Age ≤65 (AOR=3.460; 95% CI=1.511, 7.922; p=0.003), female gender (AOR=2.362; 95% CI=1.089, 5.124; p=0.030), difficult cannulation (AOR=4.527; 95% CI=2.078, 9.860; p<0.001), and patients with cholangitis (AOR=3.261; 95% CI=1.204, 8.832; p=0.020) were strongly associated with increasing Post-ERCP Pancreatitis (PEP). Advanced age has not proved to be a risk factor of difficult cannulation, and secondary cannulation techniques can be safely and efficaciously utilized for this group. CCI ≥2 and difficult cannulation are associated with increased overall adverse events rate while age ≥80 factor is not.
Sun, 25 August 2019
REVIEW Download: 36| View: 126| Comments: 0 | doi:10.20944/preprints201908.0258.v1
Online: 25 August 2019 (17:01:23 CEST)
With the continuous progress in modern medicine, the early detection rate of gastric cancer has increased, and the mortality rate has decreased. However, gastric cancer remains the third leading cause of cancer-related death worldwide, with a high recurrence rate. Metastasis is the leading cause of death and recurrence of gastric cancer, which greatly hinders treatment success. Cancer development is a complex process involving multiple sequential steps. In the metastatic cascade, local invasion may be considered an initial, crucial step in the development of a malignant tumor, which leads to distant metastasis. Epithelial-mesenchymal transformation (EMT) is one of the most important developmental processes that occur during tumor invasion. EMT confers certain basic abilities to cancer cells, such as migration, invasion and anti-apoptotic ability, thus initiating and increasing metastasis. However, little is known about the molecular mechanisms that promote EMT and gastric cancer cell metastasis. A number of recent studies have found that circular RNAs（circRNAs）are associated with gastric cancer EMT, regulating the EMT process and promoting the occurrence and development of tumors. Because of their unique continuous circular structure, circRNAs have relatively high stability in plasma and cells, making them more suitable as diagnostic biomarkers in malignant tumors. Therefore, understanding the mechanism of circRNAs in EMT in gastric cancer is an important research direction to actively prevent tumor metastasis and improve the therapeutic effect on advanced malignant tumors.
Thu, 25 July 2019
REVIEW Download: 45| View: 56| Comments: 0 | doi:10.20944/preprints201907.0282.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: HBV reactivation; lymphoma; hematology; immunosuppressive therapy; prophylaxis; hepatitis B virus; occult/active/inactive carrier
Online: 25 July 2019 (07:46:43 CEST)
It is well known that the event of hepatitis B virus reactivation can occur among patients undergoing treatment for hematological malignancies. In this paper we will present the available data regarding the risk of hepatitis B virus reactivation in this special population of immunosuppressed patients and explore the relevance of an accurate prevention and management of this condition. A computerized literature search was performed using appropriate terms arrangement, including English-written literature only or additional relevant articles. The evaluation of hepatitis B reactivation risk is a multidimensional process, which includes conducting an accurate clinical and physical history, considering the virological categories, the knowledge of the medication chosen to treat these hematological malignancies and the induced grade of immunosuppression. Adopting adequate preventive strategies and surveillance according to the current international recommendations is crucial to prevent HBVr and its dire clinical consequences (hepatitis, liver failure, interruption of lifesaving anti-neoplastic treatments). Universal HBV screening of patients scheduled to undergo treatment for hematological malignancies should be the chosen policy, and clinicians should be aware of the inherent risk of viral reactivation among the different virological categories and the classes of immunosuppressive drugs.
Thu, 4 July 2019
ARTICLE Download: 56| View: 147| Comments: 0 | doi:10.20944/preprints201907.0075.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: hepatocellular carcinoma; objective response; modified RECIST; sorafenib; hepatic arterial infusion chemotherapy
Online: 4 July 2019 (10:56:53 CEST)
Background In SILIUS (NCT01214343), combination of sorafenib and hepatic arterial infusion chemotherapy did not significantly improve overall survival in patients with advanced hepatocellular carcinoma (HCC) compared with sorafenib alone. In this study, we explored the relationship between objective response by mRECIST and overall survival (OS) in the sorafenib group, in the combination group and in all patients in the SILIUS trial. Methods Association between objective response and OS in patients treated with sorafenib (n=103), combination (n=102) and all patients (n=205) were analyzed. The median OS of responders was compared with that of non-responders. Landmark analyses were performed according to objective response at several fixed time points, as sensitivity analyses, and the effect on OS was evaluated by Cox regression analysis with objective response as a time-dependent covariate, with other prognostic factors was performed. Results In the sorafenib group, OS of responders (n = 18) was significantly better than that of non-responders (n = 78) (p < 0.0001), where median OS was 27.2 (95% CI, 16.0–not reached) months for responders and 8.9 (95% CI, 6.5–12.6) months for non-responders. HRs from landmark analyses at 4, 6, and 8 months were 0.45 (p=0.0330), 0.37 (p=0.0053), and 0.36 (p=0.0083), respectively. Objective response was an independent predictor of OS based on unstratified Cox regression analyses. In the all patients and the combination group, similar results were obtained. Conclusion In the SILIUS trial, objective response was an independent prognostic factor for OS in patients with HCC.
Mon, 1 July 2019
ARTICLE Download: 26| View: 69| Comments: 0
Subject: Medicine & Pharmacology, Gastroenterology Keywords: liver failure; microRNAs (miRNAs); placenta-derived mesenchymal stem cells (PD-MSCs); phosphatase of regenerating liver-1 (PRL-1); regenerative medicine; stem cells homing; vascular remodeling
Online: 1 July 2019 (17:00:18 CEST)
Placenta-derived mesenchymal stem cells (PD-MSCs) have been highlighted as therapeutic sources in several degenerative diseases. Recently, microRNAs (miRNAs) were mediated one of the therapeutic mechanisms of PD-MSCs in regenerative medicine. To enhance the therapeutic effects of PD-MSCs, we established functionally enhanced PD-MSCs with phosphatase of regenerating liver-1 overexpression (PRL-1(+)). However, the profile and functions of miRNAs induced by PRL-1(+) PD-MSCs in a rat model with hepatic failure prepared by bile duct ligation (BDL) remained unclear. Hence, the objectives of the present study were to analyze the expression of miRNAs and investigate their therapeutic mechanisms for hepatic regeneration via PRL-1(+) in a rat model with BDL. We selected candidate miRNAs based on microarray analysis. Under hypoxic conditions, compared with invaded naïve PD-MSCs, invaded PRL-1(+) PD-MSCs showed improved integrin-dependent migration ability through RHO family-targeted miRNA expression (e.g., hsa-miR-30a-5p, 340-5p, and 146a-3p). Moreover, rno-miR-30a-5p and 340-5p regulated engraftment into injured rat liver by transplanted PRL-1(+) PD-MSCs through the integrin family. Additionally, an increase in PDGFRA by suppressing rno-miR-27a-3p improved vascular structure in rat liver tissues after PRL-1(+) PD-MSCs transplantation. Furthermore, decreased rno-miR-122-5p was significantly correlated with increased proliferation of hepatocytes in liver tissues by PRL-1(+) PD-MSCs by activating IL-6 signaling pathway through the repression of rno-miR-21-5p. Taken together, these findings improve the understanding of therapeutic mechanisms based on miRNA-mediated stem cell therapy in liver diseases.
Thu, 27 June 2019
ARTICLE Download: 134| View: 310| Comments: 0 | doi:10.20944/preprints201906.0285.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: hepatocellular carcinoma; lenvatinib; transcatheter arterial chemoembolisation; intermediate stage; up-to-seven criteria
Online: 27 June 2019 (08:13:58 CEST)
Background: Although transcatheter arterial chemoembolisation (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC), this is a largely heterogeneous disease that includes a subgroup of patients who do not benefit from TACE. The treatment strategy for this subgroup of patients currently remains an unmet need in clinical practice. Here, we performed a proof-of-concept study that lenvatinib may be more favourable treatment option over TACE as an initial treatment in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-seven criteria. Methods: This proof-of-concept study included 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria [unresectable, beyond the up-to-seven criteria, no prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child-Pugh A liver function] were selected for the study. Propensity score matching was used to adjust for patient demographics. Results: After propensity-score matching, outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials, 1 in early access program and 15 in real world setting) and 60 patients treated with cTACE as the initial treatment was compared. The change of ALBI score from baseline to the end of treatment were -2.61 to -2.61 for 30 patients in lenvatinib group (p = 0.254) and -2.66 to -2.09 in cTACE group (p < 0.01), respectively. The lenvatinib group showed a significantly higher objective response rate (73.3% vs. 33.3%; p < 0.001) and significantly longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p < 0.001). Overall survival was significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p < 0.01). Conclusion: In patients with large or multinodular intermediate-stage HCC exceeding the up-to-seven criteria with Child-Pugh A liver function, who usually do not benefit from TACE, lenvatinib provides more favorable outcome than TACE.
Sun, 16 June 2019
ARTICLE Download: 81| View: 227| Comments: 0 | doi:10.20944/preprints201906.0151.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: ostomy; remote monitoring; stoma bag; machine learning; thermistor; capacitive sensor
Online: 16 June 2019 (17:15:26 CEST)
Over 55% of stoma patients suffer complications such as dehydration. Outcomes may be improved through communicating stoma output data to the patient and their clinical teams. Past artificial neural networks to improve accuracy in fluid level sensing were designed to account for ‘slosh’ caused by variable acceleration in one or two axes of movement. This paper describes the development of a novel sensor platform for non-invasive monitoring of stoma output in real time through incorporating a volumetric array consisting of thermistors and capacitive sensors into an ostomy appliance. Stoma output which exits the body at core temperature passes into a stoma appliance in a pattern which is dictated by water content, existing effluent within the bag and distortion of the usual bag shape. By using thermistors, a thermal boundary demarcates the accumulated level of fecal material as the effluent settles. A capacitive array allows the measurement of volume of output. The sensing components communicates via near field communication (NFC) and transmits data to a smartphone application by Bluetooth low energy (BLE). Testing of the device on 11 existing ileostomy patients with 51.6 bag hours of data found a correlation between measured volume and predictive value, supporting its use in this population.
Wed, 5 June 2019
ARTICLE Download: 44| View: 218| Comments: 0 | doi:10.20944/preprints201906.0045.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Cirrhosis; Bone marrow; Mesenchymal stem cells; Characteristics; Liver regeneration
Online: 5 June 2019 (15:43:03 CEST)
Liver cirrhosis leads to hepatic dysfunction and life-threatening conditions. Though clinical efficacy of autologous bone marrow-drived mesenchymal stem cells (BM-MSC) transplantation in alcoholic cirrhosis (AC) was demonstrated, the relevant mechanism has not been elucidated. We aimed to identify predictive factors and gene/pathways for responders after autologous BM-MSC transplantation. Fifty-five patients with biopsy-proven AC underwent autologous BM-MSC transplantation. The characteristics of responders who showed improvement in fibrosis score (≥ 1) after transplantation were compared with those of non-responders. BM-MSCs were analyzed with cDNA microarrays to identify genes and pathways that were differentially expressed in responder after transplantation. Thirty-three patients (66%) were responders. In the multivariate analysis, initial high Laennec score (p=0.007, odds ratio 3.73) and performance of BM-MSC transplantation (p=0.033, odds ratio 5.75) were predictive factors for responder. Three genes (olfactory receptor 2L8, microRNA4520-2, and chloride intracellular channel protein 3) were upregulated in responders and 11 metabolic pathways (inositol phosphate, ATP-binding cassette transporters, protein kinase signaling, extracellular matrix-receptor interaction, endocytosis, phagosome, hematopoietic cell lineage, adipocytokine, peroxisome proliferator-activated receptor, fat digestion/absorption, and insulin resistance) were upregulated in non-responders (p<0.05). BM-MSC transplantation is warranted treatment for AC patients with high Laennec score. Cell-based therapy utilizing response-relating genes or pathway can be treatment candidate.
Mon, 20 May 2019
REVIEW Download: 96| View: 181| Comments: 0 | doi:10.20944/preprints201905.0239.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: oligonucleotide therapeutics; RNA interference; antisense; aptamer; decoy; pancreatic cancer
Online: 20 May 2019 (10:12:46 CEST)
Although there is a several array of diagnostic and therapeutic choices for pancreatic cancer in recent years, a crucial medical approach for the refractory disease is still needed. Oligonucleotide therapeutics, such as those based on antisense RNAs, RNA interference, aptamers and decoys, are promising agents against pancreatic cancer because they identify a specific nucleotide sequence or protein and interfere with gene expression as molecular-targeted agents. Within just the past quarter-century, the diversity and feasibility of these drugs as diagnostic or therapeutic tools have dramatically increased. Actually, there have been several clinical and preclinical studies of oligonucleotides for patients with pancreatic cancer so far. To support the discovery of effective diagnostic or therapeutic options by using oligonucleotide-based strategies in the absence of satisfactory therapies for long-term survival and the rising trend of diseases, we summarize the current clinical trials of oligonucleotide therapeutics for pancreatic cancer patients with underlying preclinical or scientific data and focus on the possibility of oligonucleotides to target pancreatic cancer in clinical implications.
Mon, 1 April 2019
ARTICLE Download: 81| View: 157| Comments: 0 | doi:10.20944/preprints201904.0019.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Castor oil; Ascorbic acid; Bowel preparation; Polyethylene glycol
Online: 1 April 2019 (13:42:38 CEST)
Our aim was to evaluate efficacy and safety of 30mL CaO alone or plus Asc in bowel preparation before colonoscopy. Two hundred and forty six patients were allocated randomly to ingest 2L PEG with 30mL CaO, 1L PEG with 30mL CaO plus 5g Asc, or 3L PEG. We used Boston Bowel Preparation Scale (BBPS) to evaluate bowel preparation efficacy. We also determined other outcomes such as procedure time, polyp or adenoma detection rate and adverse events (AEs). Of 282 patients recruited, 36 were excluded. Groups were matched for baseline characteristics except weight (P = 0.020) and body mass index (BMI) (P = 0.003). Patient’s satisfaction were higher in 2L PEG-CaO (P = 0.016) and 1L PEG-CaO-Asc groups (P = 0·017). Patients’ compliance was 67.5%, 71.4% and 80.5% in 3L PEG, 2L PEG-CaO and 1L PEG-CaO-Asc groups (P = 0.014). Adequate bowel preparation rate was 75%, 78.57% and 53.66% in 3L PEG, 2L PEG-CaO and 1L PEG-CaO-Asc groups (P = 0.021). There were no differences in terms of remaining outcomes. Despite an increase in patients’ satisfaction and compliance, 1L PEG-CaO-Asc significantly decreased adequate bowel preparation rate. However, 2L PEG-CaO improved the patients' satisfaction and compliance and increased adequate bowel preparation rate.
Fri, 29 March 2019
REVIEW Download: 121| View: 241| Comments: 0 | doi:10.20944/preprints201903.0282.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: pancreatitis; epidemiology; diagnosis; complications; treatment; prognosis.
Online: 29 March 2019 (12:13:17 CET)
Acute pancreatitis (AP) is an inflammatory condition of the pancreas and is one of the most common ailments of the gastrointestinal system that results in significant morbidity and mortality. The main etiologic causes of AP are alcohol consumption, gallstones, hypertriglyceridemia, and biliary stones. The clinical signs and symptoms, and diagnostic criteria of AP are well established in the literature and multiple studies. Multiple scoring systems have been used to predict the severity, prognosis, and mortality associated with AP. The present review of the literature brings to light the significant and recent contributions in the etiology, risk factors, epidemiology, diagnosis, complications, prognosis and newest modalities in treatment that could be beneficial in the management of AP.
Thu, 28 March 2019
REVIEW Download: 81| View: 185| Comments: 0 | doi:10.20944/preprints201903.0267.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: hepatocellular carcinoma, gut microbiota, gut-liver axis, intestinal dysbiosis
Online: 28 March 2019 (13:43:07 CET)
Hepatocellular carcinoma (HCC), one of the leading causes of death worldwide, has a causal nexus with liver injury, inflammation, and regeneration that accumulate over decades. Observations from recent studies have accounted for the involvement of the gut-liver axis in the pathophysiological mechanism responsible for HCC. The human intestine nurtures a diversified colony of microorganisms residing in the host ecosystem. The intestinal barrier is critical for conserving the normal physiology of the gut microbiome. Therefore, a rupture of this barrier or dysbiosis cause the intestinal microbiome to serve as the main source of portal-vein endotoxins such as lipopolysaccharide, in the progression of hepatic diseases. Indeed, increased bacterial translocation is a key sign of HCC. Considering the limited number of clinical studies on HCC with respect to the microbiome, we focus on the clinical as well as animal studies involving the gut microbiota with the current understandings of the mechanism by which the intestinal dysbiosis promotes hepatocarcinogenesis. Future research might offer mechanistic insights into the specific phyla targeting the leaky gut, as well as microbial dysbiosis, and their metabolites, as key pathways that drive HCC-promoting microbiome-mediated liver inflammation and fibrosis, thereby restoring the gut barrier function.
Mon, 11 March 2019
ARTICLE Download: 153| View: 317| Comments: 0 | doi:10.20944/preprints201903.0128.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Liver cirrhosis; epidemiology; etiology; risk factors; pathophysiology; diagnosis.
Online: 11 March 2019 (09:44:18 CET)
Liver cirrhosis is a chronic disease that is characterized by the presence of fibrosis and regeneration of nodules in the liver whose consequences are the development of portal hypertension and liver failure. Cirrhosis arises from a wide variety of chronic diseases, which progresses slowly after years or decades. Liver cirrhosis is a public health problem. It is usually associated with viral hepatitis, consumption of alcohol, metabolic syndrome, autoimmune processes, storage diseases, toxic substances, and medications. Cirrhosis is the fourteenth most common cause of death in adults throughout the world, the fourth in Europe and the ninth in the United States. The prevalence of this disease is underestimated because it is symptomatic it is not diagnosed in initial stages, and it usually goes to the decompensated stage at a rate of 5 to 7% per year. We review here the epidemiology, pathophysiology, etiology, and diagnosis of liver cirrhosis.
Mon, 25 February 2019
REVIEW Download: 135| View: 198| Comments: 0 | doi:10.20944/preprints201902.0220.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Acute pancreatitis; Etiology; Biliary pancreatitis; Systematic review; Meta-analysis
Online: 25 February 2019 (08:58:59 CET)
Introduction: Cholelithiasis and consumption of alcohol are the most frequent causes of acute pancreatitis (AP), accounting for about 30 to 40% of the cases, respectively. The frequency of acute biliary pancreatitis is high in a certain population in Brazil. Objective: To estimate the global frequencies of acute biliary pancreatitis (ABP), acute alcoholic pancreatitis (AAP) and the cases considered as acute idiopathic pancreatitis (AIP) in studies published from October 2006 to December 31, 2018. Methods: A systematic review of observational studies was performed from October 2006 to December 31, 2018. A meta-analysis by the random effects model was used to calculate the frequencies of global ABP, AIP and AAP and subgroups. Results: Forty-six studies representing 2,341,007 AP cases were included in 36 countries. The overall estimate for acute biliary pancreatitis (ABP) was 41.6% (95% CI 39.2-44.1), followed by acute alcoholic pancreatitis (AAP) with 20.5% (95% CI) 16.6- 24.6) and acute idiopathic pancreatitis (AIP) in 18.3% (95% CI 15.1-27.7). Conclusion: ABP is the most prevalent etiology of AP, being two times more frequent than second-placed pancreatitis. Latin America has a frequency for ABP much higher than the rest of the world. The importance of the etiologic diagnosis is the treatment of the cause for prevention of recurrence.
Tue, 12 February 2019
ARTICLE Download: 64| View: 556| Comments: 0 | doi:10.20944/preprints201902.0100.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: obesity; diabetes; body weight; body composition; glucose tolerance; insulin tolerance; incretin; energy expenditure
Online: 12 February 2019 (10:37:42 CET)
Background/Goals: The gut hormone PYY secreted from intestinal L-cells has been implicated in the mechanisms of satiation via Y2-receptor (Y2R) signaling in the brain and periphery and is a major candidate for mediating the beneficial effects of bariatric surgery on appetite and body weight. Methods: Here we assessed the role of Y2R signaling in the response to low- and high-fat diets and its role in the effects of Roux-en-Y gastric bypass (RYGB) surgery on body weight, body composition, food intake, energy expenditure and glucose handling, in global Y2R-deficient (Y2RKO) and wildtype mice made obese on high-fat diet. Results: Both male and female Y2RKO mice responded normally to low- and high-fat diet in terms of body weight, body composition, fasting levels of glucose and insulin, as well as glucose and insulin tolerance for up to 30 weeks of age. Contrary to expectations, obese Y2RKO mice also responded similarly to RYGB compared to WT mice for up to 20 weeks after surgery, with initial hypophagia, sustained body weight loss, and significant improvements in fasting insulin, glucose tolerance, HOMA-IR, and liver weight compared to sham-operated mice. Furthermore, non-surgical Y2RKO mice weight-matched to RYGB showed the same improvements in glycemic control as Y2RKO mice with RYGB that were similar to WT mice. Conclusions: PYY signaling through Y2R is not required for the normal appetite-suppressing and body weight-lowering effects of RYGB in this global knockout mouse model. Potential compensatory adaptations of PYY signaling through other receptor subtypes or other gut satiety hormones such as GLP-1 remain to be investigated.
Thu, 7 February 2019
ARTICLE Download: 74| View: 624| Comments: 0 | doi:10.20944/preprints201902.0070.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Helicobacter pylori, aspirin, atrophic gastritis, intestinal metaplasia, microRNA, methylation
Online: 7 February 2019 (11:30:17 CET)
The risk of gastric cancer (GC) declines after Helicobacter pylori (H. pylori) eradication and long-term aspirin use. We evaluated the effects of H. pylori eradication (Cohort 1) and aspirin use (Cohort 2) on the methylation of microRNAs (miRNAs) such as miR-34c, miR-124a-3, miR-129-2, and miR-137 in the gastric mucosa with and without GC, i.e., atrophic mucosa (AM) and intestinal metaplasia (IM). DNA was isolated from AM and IM separately using laser caption microdissection. In Cohort 1, H. pylori eradication was associated with a significant reduction of miR-124a-3 methylation only in AM, but not in IM. miR-129-2 methylation in AM may be a surrogate marker of GC in H. pylori-infected patients. In Cohort 2, aspirin did not reverse miRNA methylation in either AM or IM irrespective of H. pylori infection. miR-129-2 methylation in AM was an independent predictive marker of GC in H. pylori-infected but not -eradicated patients. These results indicate that H. pylori eradication and aspirin use were less effective in improving methylation in IM compared with AM; thus, these interventions are recommended at an early stage prior to the development of IM to prevent GC development.
Mon, 14 January 2019
REVIEW Download: 74| View: 167| Comments: 0 | doi:10.20944/preprints201901.0133.v1
Online: 14 January 2019 (11:25:46 CET)
Early detection of pancreatic ductal adenocarcinoma (PDAC) requires further examination after selecting cases with risk factors for the condition, such as family history, hereditary pancreatic carcinoma syndrome, intraductal papillary mucinous neoplasms, or chronic pancreatitis. The Japan Study Group on the Early Detection of Pancreatic Cancer has investigated and clarified the clinicopathological features for the early diagnosis of PDAC. Further approaches for the early diagnosis of PDAC are warranted.
Wed, 26 December 2018
CASE REPORT Download: 50| View: 167| Comments: 0 | doi:10.20944/preprints201812.0316.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Stomach, giant, gastrointestinal stromal tumor; treatment
Online: 26 December 2018 (12:29:23 CET)
Gastrointestinal stromal tumors are the mostly seen mesenchymal tumors of the gastrointestinal system and mostly seen at the stomach. We report a case of giant gastrointestinal stromal tumor of the stomach in a 71-year-old woman. The physical examination and radiological findings revealed that a giant mass occupied most of the abdominal cavity. The patient underwent an en-block resection of this giant mass with partial resection of the distal stomach and transverse colon and, reconstruction with gastro-jejunostomy and end-to end colo-colic anatomoses. The histopathologic diagnosis was revealed as gastrointestinal stromal tumor of the stomach. We suggest that complete surgical resection is the only effective radical treatment approach for giant gastrointestinal stromal tumors of the stomach.
CASE REPORT Download: 43| View: 161| Comments: 0 | doi:10.20944/preprints201812.0315.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Duodenum, gastrointestinal stromal tumor; treatment
Online: 26 December 2018 (12:25:28 CET)
Gastrointestinal stromal tumors are the mostly seen mesenchymal tumors of the gastrointestinal system. This rare tumor in duodenum is seen 5%. The diagnosis and treatment is hard because of its rarity and location. Case: A 63-year-old man with a solid mass at the third part of the duodenum, and local segmental resection of the tumor was performed. The histopathology was reported as gastrointestinal stromal tumor of the duodenum with negative surgical margins. Discussion: Gastrointestinal stromal tumors at the duodenum are seen rarely. They can be asymptomatic or may involve symptoms of upper GI bleeding and abdominal pain at presentation. Because of the misleading clinical presentation the differential diagnosis may be difficult. Tumors less than 2 cm can be followed by endoscopic ultrasound. Local segmental resection with 1cm clear margin is the treatment choice.
Thu, 20 December 2018
CASE REPORT Download: 51| View: 144| Comments: 0 | doi:10.20944/preprints201812.0244.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: robotic surgery, da Vinci Xi, rectal cancer, vaginal extraction
Online: 20 December 2018 (09:47:08 CET)
Introduction: Novel robotic surgery systems (da Vinci Xi) are superior to classical open and laparoscopic techniques with its clear and three-dimensional view. We aimed to present the first case low anterior resection of rectal cancer and vaginal specimen extraction with Da Vinci Xi.Case: A 75-year-old female patient with rectum adenocarcinoma was undergone robotic-assisted low anterior resection (LAR) of the rectum, vaginal removal of the specimen, colorectal anastomosis and loop ileostomy. The operation time was 190 minutes. There were no postoperative complications. Pathological tumor stage was stage pT1N0 with negative proximal, distal and radial resection margins. The patient was discharged on the third postoperative day.Conclusion: Robot-assisted LAR, total mesorectal excision, vaginal removal of the specimen, colorectal anastomosis, and loop ileostomy can be performed easily and safely with Da Vinci Xi at early stage rectal cancer. And the vaginal extraction of the specimen avoids us from a traditional abdominal incision.
CASE REPORT Download: 52| View: 137| Comments: 0 | doi:10.20944/preprints201812.0242.v1
Online: 20 December 2018 (09:14:40 CET)
Colonic lipomas are usually seen as small dimensions in the cecum and ascending colon of elderly women. Many of colon lipomas are asymptomatic and diagnosed incidentally during endoscopy or surgery. As diameter increases it can cause symptoms such as bleeding, obstruction or intussusceptions. 53 years old female patient was admitted to the emergency department with ongoing intermittent abdominal pain more significantly over the past year with nausea and vomiting. On routine physical examinations more pronounced abdominal tenderness and rebound was observed in the right lower quadrant. At blood count leucocytosis was measured as 15,300. Other biochemical parameters were normal. Air-fluid levels were detected on abdominal graphy, bowel dilatation and a mass of 7x5x4 cm in diameters in cecum, compatible with lipoma reported by ultrasound and computed tomography,The patientunderwent laparotomy the mass which cause the lumen almost completely obstructed was palpated in the cecum with proximal bowel dilatation. A right hemicolectomy and ileotransversostomy was performed. Histopathologic examination of the resected specimen was reported as lipoma consisting of grossly compatible with yellow microscopic fatty cells. On the fifth postoperative day the patient was discharged uneventfully without any complaints and complications. We report a case of giant cecal lipoma causing intussusseption who admitted to our clinic and discharged successfully.
Tue, 20 November 2018
REVIEW Download: 79| View: 109| Comments: 0 | doi:10.20944/preprints201811.0511.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: coeliac disease; Crohn’s disease; dysplasia; histotype; overall survival; tumor infiltrating lymphocyte.
Online: 20 November 2018 (16:43:14 CET)
Small bowel carcinomas (SBC) are uncommon neoplasms, whose predisposing conditions include hereditary syndromes and immune-mediated intestinal disorders, including coeliac disease (CD) and Crohn’s disease (CrD). Although both CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) arise from an inflammatory background, they differ substantially in tumour cell phenotype, frequency of microsatellite instability and nuclear β-catenin expression, as well as in prognosis. For these patients, high tumor-infiltrating lymphocyte density and glandular/medullary histotype represent independent positive prognostic factors. Dysplasia adjacent to SBC is rare and characterized by intestinal phenotype and nuclear β-catenin in CD, while it is frequent and typified by gastro-pancreatobiliary marker expression and preserved membranous β-catenin in CrD. Recent evidence suggests that Epstein-Barr virus-positive dysplasia and SBC, albeit exceptional, do exist and are associated with CrD. In this review we summarize the novel pathological and molecular insights of clinical and therapeutic interest to guide the care of CD-SBC and CrD-SBC.
ARTICLE Download: 88| View: 118| Comments: 0 | doi:10.20944/preprints201811.0488.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Crohn’s disease; NOD2 gene; variation; WES.
Online: 20 November 2018 (08:44:01 CET)
The NOD2 gene, involved in innate immune responses to bacterial peptidoglycan, has been found to be strongly associated with Crohn’s Disease, with an Odd Ratio ranging from 3 to 36. Families with 3 or more CD affected patients were related to high frequency of NOD2 gene variations as R702W, G908R, 1007fs and were reported in EPIMAD Registry. However, some rare CD multiplex families were described without identification of common NOD2 linked-to-disease variations. In order to identify new genetic variation(s) with a major effect on Crohn’s disease (CD), whole exome sequencing was performed in available subjects comprising 4 patients on 2 generations affected with Crohn’s disease without R702W and G908R variation, and 3 unaffected related subjects. A new rare and not yet reported missense variation of the NOD2 gene, the N1010K, was detected and co-segregated across affected patients. In silico evaluation and modeling highlighted evidences for a deleterious effect of the N1010K variation regarding CD. Moreover cumulative characterization of N1010K and 1007fs as compound heterozygous state in two more severely CD family members strongly suggesting that the N1010K should be a new risk factor involved in Crohn’s disease genetic susceptibility.
Thu, 15 November 2018
BRIEF REPORT Download: 58| View: 50| Comments: 0 | doi:10.20944/preprints201811.0341.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: colorectal cancer; new technologies; palliative care for colorectal cancer patients; stenting
Online: 15 November 2018 (04:59:37 CET)
BACKGROUND: Endoscopic placement of Self Expandable Metal Stents to relieve malignant colorectal obstruction has become a common therapeutic advancement in clinical practice. MATERIAL: In a 16 year period 167 patients had endoscopic placement of a Self Expandable Metal Stent in a center where gastroenterologists and surgeons cooperate in a daily basis, discussing indications. RESULTS: There was no operative mortality and no major complication in placement of the stent. Technical and clinical success was respectively 95.1% and 92.9%. Consultation among specialists changed the preoperative indication in 60 patients, during the same time period. CONCLUSIONS: Self expandable metal stents placement represents an important tool to treat patients with obstructing colorectal cancer and complications after colorectal resection . A proper training is required, and this training in operative endoscopy is not always available and possible. In this scenario, a close collaboration among specialists in selecting the most appropriate operative procedure is essential and brings to better results.
Wed, 24 October 2018
REVIEW Download: 161| View: 132| Comments: 0 | doi:10.20944/preprints201810.0554.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: gut brain axis; microbiota; functional gastrointestinal disorders
Online: 24 October 2018 (07:41:58 CEST)
The central nervous system (CNS) and the human gastrointestinal (GI) tract communicate through the gut-brain axis (GBA). Such communication is bi-directional and involves neuronal, endocrine and immunological mechanisms. The scientific data are mounting that gut microbiota is a source of a number of neuroactive and immunocompetent substances, which shape the structure and function of brain regions involved in control of emotions, physical activity and cognition. Most of GI maladies are associated with altered transmission within the GBA and influenced both by genetic and environmental factors. Current treatment protocols widely advocated for the treatment of GI disorders may positively or adversely affect the composition of intestinal microbiota with diverse impact on therapeutic outcome. The alterations of gut microbiota have been associated with mood and depressive disorders. and mental health is frequently altered in the course of many GI and non-GI ailments. Deregulation of the GBA may constitute a grip point for the development of diagnostic tools and personalized microbiota-based therapy. For example next generation sequencing (NGS) offers detailed analysis of microbiome footprints in patients with mental and GI disorders. Psychobiotics are new class of beneficial bacteria, with documented efficacy in the treatment of gut-brain axis disorders.
Tue, 23 October 2018
ARTICLE Download: 111| View: 133| Comments: 0 | doi:10.20944/preprints201810.0521.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: alcohol-induced Golgi disorganization; Golgi recovery; giantin; hepatic proteins; ethanol withdrawal
Online: 23 October 2018 (06:10:04 CEST)
Background: In hepatocytes and alcohol-metabolizing cultured cells, Golgi undergoes ethanol (EtOH)-induced disorganization. Periniclear and organized Golgi is important in liver homeostasis, but how the Golgi remains intact is unknown. Work from our laboratories showed that EtOH-altered cellular function could be reversed after alcohol removal; we wanted to determine whether this recovery would apply to Golgi. Methods: We used alcohol-metabolizing HepG2 (VA-13) cells (cultured with or without EtOH for 72 h) and rat hepatocytes (control and EtOH-fed (Lieber-DeCarli diet). For recovery, EtOH was removed and replenished with control medium (48 hours for VA-13 cells) or control diet (10 days for rats). Results: EtOH-induced Golgi disassembly was associated with de-dimerization of the largest Golgi matrix protein giantin, along with impaired transport of selected hepatic proteins. After recovery from EtOH, Golgi regained their compact structure, and alterations in giantin and protein transport were restored. In VA-13 cells, when we knocked down giantin, Rab6a GTPase or non-muscle Myosin IIB, minimal changes were observed in control conditions, but post-EtOH recovery was impaired. Conclusions: These data provide a link between Golgi organization and plasma membrane protein expression and identify several proteins whose expression is important to maintain Golgi structure during the recovery phase after EtOH administration.
Mon, 22 October 2018
ARTICLE Download: 77| View: 81| Comments: 0 | doi:10.20944/preprints201810.0496.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: zinc, HCC, liver function, Zn concentration
Online: 22 October 2018 (12:38:25 CEST)
Background and Aim: Zinc plays a pivotal role in various zinc enzymes, resulting in the maintenance of liver function. Patients with chronic liver diseases (CLDs) usually have lower concentrations of zinc, which decrease further as liver fibrosis progresses. It remains unknown whether long-term zinc supplementation improves liver function and reduces the risk of hepatocellular carcinoma (HCC) development. Patients and Methods: Two hundred sixty-seven patients with CLDs who received a zinc preparation (Zn-group; 196 patients), or who did not receive zinc (no Zn-treatment group; 71 patients) were retrospectively analyzed in this study. The Zn-group was divided into 4 groups according to their serum Zn concentrations at 6 months after the start of Zn treatment. Results: Liver function significantly deteriorated in the no Zn-treatment group, while no notable change was observed in the Zn-group. The cumulative incidence rates of events and HCC at 3 years were lower in the Zn-group (9.5%, 7.6%) than in the no Zn-treatment group (24.9%, 19.2%) (p<0.001). According to the serum Zn concentrations, the cumulative incidence rates of events and HCC were significantly decreased in patients with Zn concentrations ≥ 70 µg/dl (p<0.001). Conclusion: Zinc supplementation appears to be effective at maintaining liver function and suppressing events and HCC development, especially among patients whose Zn concentration is greater than 70 µg/dl.
Fri, 19 October 2018
REVIEW Download: 108| View: 92| Comments: 0 | doi:10.20944/preprints201810.0450.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: hepatocellular carcinoma; natural killer cell
Online: 19 October 2018 (11:09:02 CEST)
Hepatocellular carcinoma (HCC) is currently the third leading cause of malignancy-related mortalities worldwide. Natural killer (NK) cells are involved in the critical role of first line immunological defense against cancer development. Defects in NK cell functions are recognized as important mechanisms for immune evasion of tumor cells. NK cell function appears to be attenuated in HCC, and many previous reports suggested that NK cells play a critical role in controlling HCC, suggesting that boosting the activity of dysfunctional NK cells can enhance tumor cell killing. However, the detailed mechanisms of NK cell dysfunction in tumor microenvironment of HCC remain largely unknown. A better understanding of the mechanisms of NK cell dysfunction in HCC will help in the NK cell-mediated eradication of cancer cells and prolong patient survival. In this review, we describe the various mechanisms underlying NK cell dysfunction in HCC. Further, we summarize current advances in the approaches to enhance endogenous NK cell function and in adoptive NK cell therapies, to cure this difficult-to-treat cancer.
Thu, 18 October 2018
REVIEW Download: 124| View: 108| Comments: 0 | doi:10.20944/preprints201810.0429.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Copper; fructose; Kupffer cell (KC); iron; non-alcoholic fatty liver disease (NAFLD); metabolic syndrome; gut microbiota
Online: 18 October 2018 (16:57:06 CEST)
Compelling epidemiologic data support the critical role of dietary fructose in the epidemic of obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). The metabolic effects of fructose on the development of metabolic syndrome and NAFLD are not completely understood. High fructose intake impairs copper status, and copper-fructose interactions have been well documented in rats. Altered copper-fructose metabolism leads to exacerbated experimental metabolic syndrome and NAFLD. A growing body of evidence has demonstrated that copper levels are low in NAFLD patients. Moreover, hepatic and serum copper levels are inversely correlated with the severity of NAFLD. Thus, high fructose consumption and low copper availability are considered two important risk factors in NAFLD. However, the causal effect of copper-fructose interactions as well as the effects of fructose intake on copper status remain to be evaluated in humans. The aim of this review is to summarize the role of copper-fructose interactions in the pathogenesis of the metabolic syndrome and discuss the potential underlying mechanisms. This review will shed light on the role of copper homeostasis and high fructose intake and point to copper-fructose interactions as novel mechanisms in the fructose induced NAFLD.
ARTICLE Download: 77| View: 105| Comments: 0 | doi:10.20944/preprints201810.0423.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Crohn’s disease, dietary intake, malnutrition, Mediterranean diet
Online: 18 October 2018 (12:03:28 CEST)
The purpose of this study was to (a) compare macro- and micronutrient intakes between male and female CD patients (b) compare micronutrient intakes of CD patients to a representative population of healthy individuals, and; (c) describe Mediterranean diet scores (P-MDS) of male and female CD patients in remission recruited from an IBD clinic in Calgary, AB. Consecutive patients with ileal and/or colonic CD in endoscopic remission were recruited for participation in this cross-sectional study. Sixty-seven patients were enrolled, with a mean age of 45, and a BMI ≥ 25. Compared with the healthy population, patients with CD had similar energy, protein, carbohydrate and total fat intake. However, PUFA, omega-6 and 3 and MUFA were lower in CD patients and dietary fibre intake was higher. Vitamins C, D, thiamin, niacin, magnesium, phosphorus, zinc and potassium were all significantly lower in all CD patients compared to a healthy population. Few patients with CD met P-MDS criteria for olive oil, vegetable, legumes, and fish intake or consuming Sofrito sauce (mean 4.5, SD=1.1 in males and 4.7, SD=1.8 in females). Patients with CD in remission have suboptimal dietary intakes and patterns and targeted dietary interventions may be beneficial in this population to improve intake.
Mon, 15 October 2018
REVIEW Download: 137| View: 86| Comments: 0 | doi:10.20944/preprints201810.0324.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: celiac disease; gluten-free diet; effectiveness; adherence; nutritionists; clinic; serology; duodenal biopsies; structured questionnaires; peptides derived from gluten in feces and urine.
Online: 15 October 2018 (16:27:32 CEST)
Celiac disease (CD) is a genetically conditioned autoimmune process that appears in susceptible people. It can affect people of any age, and slightly predominates in females. It has a fairly homogenous global distribution, with an average prevalence of 1-2%, the frequency having increased in recent decades. The only effective treatment is a strict and permanent gluten-free diet (GFD), although the level of compliance with it is poor, at about 50% of cases. To monitor the effectiveness of the GFD, several procedures involving various approaches are employed: a) periodic interviews by nutritionists; b) clinical follow-up; c) serological controls of specific antibodies; d) endoscopies with collection of duodenal biopsies; e) structured questionnaires; f) determination of gluten peptides derived from gluten in feces and/or urine. All of these procedures are useful when applied, alone or in combination, depending on the cases. Some patients will only need to consult to their doctors, while others will require a multidisciplinary approach to assess their compliance with the GFD. In children, normalization of duodenal mucosa was achieved in 95% of cases within 2 years, while it is more delayed in adults, whose mucosa take longer to heal completely.
Wed, 10 October 2018
ARTICLE Download: 130| View: 212| Comments: 0 | doi:10.20944/preprints201810.0201.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: hepatitis c viruses; hepatitis e virus; dentists
Online: 10 October 2018 (05:21:20 CEST)
Health care workers (HCWs), specifically dentists, are at the front line for acquiring blood-borne virus infections. The highest proportion of occupational transmission is through percutaneous injuries via hollow-bore needles. Several studies around the world have reported that hepatitis viruses and human immunodeficiency virus are the main pathogens for most cases of occupationally acquired blood-borne infection. We aim to investigate the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis E virus (HEV), and human immunodeficiency virus (HIV) among Mexican dentists. Methods. We included 159 dentists who attended the annual meeting at the Medica Sur Clinic & Foundation held in Mexico City in May 2016. A survey was applied in order to obtain data of occupational exposure to blood-borne viruses (BBV). Serum samples were screened serologically using enzyme-linked immunosorbent assays. Results. Two dentists (1.2%) were positive for antibodies against HCV antigen, one (0.6%) was positive for antibodies against HBV antigen and three (1.8%) were positive for the detection of IgG antibodies against HEV. Two cases (1.2%) were positive for antibodies against HIV. Conclusions. The infection by HEV was the most prevalent among dentists. However, the prevalence of BBV in dentists was similar to that in the general population.
Sat, 29 September 2018
ARTICLE Download: 91| View: 125| Comments: 0 | doi:10.20944/preprints201809.0590.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: acute appendicitis; complicated appendicitis; laparoscopic appendectomy; intraabdominal abscess
Online: 29 September 2018 (10:51:00 CEST)
Background: To investigate the preoperative clinical and radiological factors that predict the development of a postoperative intraabdominal abscess (IAA) in patients with acute appendicitis who were treated by laparoscopic appendectomy (LA). Methods: Two hundred sixteen patients with pathologically proven acute appendicitis underwent LA between January 2013 and March 2018 in our department. Of these, 147 patients were diagnosed with complicated appendicitis (CA) (CA group), while the other 69 patients were diagnosed with simple appendicitis (SA) (SA group). We compared the perioperative clinical and radiographic factors between the two groups and investigated the predictive factors of postoperative IAA. Results: Sixteen patients developed postoperative IAA in the CA group, while no patients did in the SA group. The univariate analysis revealed that time from onset to surgery more than 3 days (p = 0.011), the preoperative CT finding of periappendiceal fluid (p = 0.003), abscess (p < 0.001), and free air (p <0.001), operation time more than 120 minutes (p = 0.023) and placement of a drainage tube (p <0.001) were significantly associated with the development of IAA. Multivariate analysis revealed that the preoperative CT finding of free air was independently associated with the development of IAA (p = 0.007, odds ratio = 5.427). Conclusions: IAA was developed predominantly in the patients with CA. Preoperative CT findings of free air was found to be an independent predictor for the development of IAA. Surgeons should be meticulous in managing the postoperative course of patients with this finding.
Thu, 20 September 2018
REVIEW Download: 220| View: 206| Comments: 0 | doi:10.20944/preprints201809.0397.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: lactobacilli; bifidobacilli; arthritis; inflammatory bowel; microbiome; metabolomics; aryl hydrocarbon reductase; adenosine; histamine; short chain fatty acid
Online: 20 September 2018 (05:12:00 CEST)
Probiotics have been used to ameliorate gastrointestinal symptoms since ancient times. Over the past 40 years, probiotics have been shown to exert major effects on the immune system, both in vivo and in vitro. This interaction is clearly linked to gut microbes, their polysaccharide antigens, and key metabolites produced by these bacteria. At least four metabolic pathways have been implicated in mechanistic studies of probiotics, based on carefully studied animal models. Microbial-immune system crosstalk has been linked to short chain fatty acid production and signaling, tryptophan metabolism and the activation of aryl hydrocarbon receptors, nucleoside signaling in the gut, and activation of the intestinal histamine-2 receptor. Several randomized controlled trials have now shown that microbial modification by probiotics may improve gastrointestinal symptoms and multi-organ inflammation in rheumatoid arthritis, ulcerative colitis, and multiple sclerosis. Future work will need to carefully assess safety issues, selection of optimal strains and combinations, and attempts to prolong the duration of colonization of beneficial microbes.
Fri, 14 September 2018
REVIEW Download: 355| View: 297| Comments: 0 | doi:10.20944/preprints201809.0268.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Liver; NAFLD; NASH; Biomarkers; Reactive Species; Oxidative Stress; Lipid Peroxidation; Antioxidants.
Online: 14 September 2018 (14:11:31 CEST)
Non-Alcoholic Fatty Liver Disease (NAFLD) is a term that covers a range of hepatic disorders involving fat deposits in the liver. NAFLD begins with simple steatosis and progresses into non-alcoholic steatohepatitis (NASH) characterised by inflammation, fibrosis, apoptosis, oxidative stress, lipid peroxidation, mitochondrial dysfunction and release of adipokines and pro-inflammatory cytokines. Oxidative stress and antioxidants are known to play a vital role in the pathogenesis and severity of NAFLD/NASH. A number of oxidative stress and antioxidant markers are employed in the assessment of the pathological state and progression of the disease. In this article, we review several biomarkers of oxidative stress and antioxidants that have been measured at clinical and experimental levels. The levels/ activity in various models reviewed are also included. Also included is a comprehensive description of oxidative stress, sources and contribution to the pathogenesis of NAFLD/NASH
Fri, 7 September 2018
ARTICLE Download: 157| View: 175| Comments: 0 | doi:10.20944/preprints201809.0133.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: cell migration; hepatic stellate cell; TGF-β1; Rap1; RhoA; NF-κB
Online: 7 September 2018 (12:19:49 CEST)
Although the migration of hepatic stellate cells (HSCs) is important for hepatic fibrosis, the regulation of HSC migration is poorly understood. Interestingly, transforming growth factor (TGF)-β1 induces monocyte migration to sites of injury or inflammation in the early phase but inhibits cell migration in the late phase. In this study, we investigated the role of RhoA signaling in TGF-β1-induced HSC migration. We found that TGF-β1 increased the protein and mRNA levels of α-SMA and collagen type I in HSC-T6 cells. The level of RhoA-GTP in TGF-β1-stimulated cells was significantly higher than that in control cells. Moreover, cofilin phosphorylation and F-actin formation was more strongly detected in TGF-β1-stimulated cells than in control cells. Additionally, TGF-β1 induced the activation of NF-κB and the expression of extracellular matrix proteins and several cytokines in HSC-T6 cells. The active form of Rap1 (Rap1 V12) suppressed RhoA-GTP levels, whereas the dominant negative form of Rap1 (Rap1 N17) augmented RhoA-GTP levels. Therefore, we confirmed that Rap1 regulates RhoA activation in TGF-β1-stimulated HSC-T6 cells. These findings suggest that TGF-β1 regulates Rap1, resulting in RhoA suppression, NF-κB activation and F-actin formation during the migration of HSCs.
Thu, 23 August 2018
REVIEW Download: 122| View: 154| Comments: 0 | doi:10.20944/preprints201807.0525.v2
Subject: Medicine & Pharmacology, Gastroenterology Keywords: 4-Hydroxynonenal; lipid peroxidation; redox balance; oxidative stress; stomach; peptic ulcer; gastritis; Helicobacter pylori; gastric cancer; non-steroid anti-inflammatory drugs-induced gastropathy
Online: 23 August 2018 (04:24:43 CEST)
Maintenance of integrity and function of the gastric mucosa (GM) requires a high regeneration rate of epithelial cells during the whole life span. The health of the gastric epithelium highly depends on redox homeostasis, antioxidant defense and activity of detoxifying systems within the cells as well as robustness of blood supply. Bioactive products of lipid peroxidation, in particular second messengers of free radicals, the bellwether of which is 4-hydroxynonenal (HNE), are important mediators in physiological adaptive reactions and signaling but they are also thought to be implicated in the pathogenesis of numerous gastric diseases. Molecular mechanisms and consequences of increased production of HNE and its protein adducts in response to stressors during acute and chronic gastric injury are well studied. However, several important issues related to the role of HNE in gastric carcinogenesis, tumor growth and progression, the condition of GM after eradication of Helicobacter pylori, or the relevance of antioxidants for HNE-related redox homeostasis in GM still need more studies and new comprehensive approaches. In this regard, preclinical studies and clinical intervention trials are required, which should also include the use of state-of-the-art analytical techniques such as HNE determination by immunohistochemistry and ELISA as well as modern mass-spectroscopy methods.
Fri, 27 July 2018
REVIEW Download: 120| View: 171| Comments: 0 | doi:10.20944/preprints201807.0525.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: 4-Hydroxynonenal; lipid peroxidation; redox balance; oxidative stress; stomach; peptic ulcer; gastritis; Helicobacter pylori; gastric cancer; non-steroid anti-inflammatory drugs-induced gastropathy
Online: 27 July 2018 (03:07:19 CEST)
The integrity, high functional activity and sufficient regeneration rate of gastric mucosa (GM) in harsh conditions is very challenging pathophysiological demand. The health of gastric epithelium highly depends of efficiency of redox balance maintenance, antioxidant defense and activity of detoxifying systems within the cells as well as robustness of blood supply. Bioactive products of lipid peroxidation, in particular second messengers of free radicals, the bellwether of which is 4-hydroxynonenal (HNE), are important mediators in (patho)physiological adaptive reactions, cells signaling, and are also implicated in pathogenesis of numerous gastric diseases. However, while mechanisms and consequences of HNE and its protein adducts production in response to strong stressors during acute and chronic gastric injury are well studied, many other important issues related to gastric carcinogenesis, tumor growth and progression, the condition of GM after eradication of Helicobacter pylori, the relevance of antioxidants for HNE-related redox homeostasis in GM and many other still need extensive studies and new comprehensive approaches. Therefore, in order to address existing issues preclinical studies and clinical intervention trials are required, which should include also determination of HNE preferably by immunohistological and specific HNE-His ELISA analyses.
Fri, 13 July 2018
ARTICLE Download: 263| View: 200| Comments: 0 | doi:10.20944/preprints201807.0247.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: vitamin D receptor, cytokines, miR-346, primary sclerosing cholangitis, colorectal cancer
Online: 13 July 2018 (17:36:38 CEST)
Primary sclerosing cholangitis (PSC) is a cholestatic liver disorder frequently associated with ulcerative colitis (UC). Patients with PSC and UC have higher risk of colorectal neoplasia than patients with UC without PSC. Oncogenic properties of micro RNA 346 (miR-346) have been recently reported. In this study we investigated expressions of miR-346 and its two target genes i.e. the receptor of vitamin D (VDR) and the tumor necrosis factor α (TNF-α), which are known to modulate carcinogenesis. Biopsies from ascending and sigmoid colon were obtained from patients with PSC with and without UC, patients with UC and healthy controls. MiR-346 expression was increased in ascending but not sigmoid colon of patients with PSC and UC when compared to other analyzed groups (p<0.001 for all). In patients with UC an exceptionally low colonic expression of miRNA-346 was accompanied by the increase in VDR expression, and the extensive upregulation of TNF-α gene which protein product is known to be cytotoxic to tumor cells at high concentration. In summary, a substantial upregulation of miRNA-346 in ascending colon of patients with PSC and UC may be responsible for the inhibition of VDR and TNF-α signaling -pathway which may result in an inadequate suppression of neoplasia.
Mon, 25 June 2018
REVIEW Download: 197| View: 249| Comments: 0 | doi:10.20944/preprints201806.0390.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Inflammatory Bowel Disease (IBD); colitis; PET; SPECT; microbiota; cytokine; chemokine; inflammation
Online: 25 June 2018 (12:57:48 CEST)
Inflammatory Bowel Disease (IBD) is characterized by chronic remitting and relapsing inflammation of the lower gastrointestinal tract. The etiology underlying IBD remains unknown but is thought to involve a hypersensitive immune response to environmental antigen, including the microbiota. Diagnosis and monitoring of disease is heavily reliant on endoscopy, which is invasive and does not provide information regarding specific mediators. This review describes recent developments in imaging of IBD with a focus on PET and SPECT imaging of inflammatory mediators, and how this may be applied to the microbiota.
Tue, 8 May 2018
REVIEW Download: 331| View: 652| Comments: 0 | doi:10.20944/preprints201805.0129.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: BET inhibitors; HDAC inhibitors; pancreatic cancer; aberrant transcription; enhancers; transcription factors; distal regulatory elements; MYC; FOXA1; BRD4
Online: 8 May 2018 (10:47:27 CEST)
While the mortality rates of cancer are generally declining, pancreatic cancer persists to be an exception with a 5-year-survival rate of less than 7%. Late diagnosis and resistance to conventional therapies contribute to high mortality rates in spite of the remarkable recent advances in cancer management and research. Consequently, there is an urgent need to find new and unconventional therapeutic targets to improve prognosis and survival of pancreatic cancer patients. In this review, we discuss the transcriptional effects of the most widely used epigenetic inhibitors in pancreatic cancer focusing on Bromodomain and Extraterminal domain (BET) and Histone Deacetylase (HDAC) inhibitors, which are currently highly promising therapeutic options. We suggest that these inhibitors can be better utilized at lower doses which exploit their transcriptional modulatory effects on pancreatic cancer transcriptional programs directed by specific factors such as MYC and FOXA1, rather than simply based on their anti-proliferative effects. This approach can potentially help avoid the intolerable adverse events frequently elicited by the use of these treatments at higher doses. In particular, we underscore the crucial role of distal regulatory elements in mediating the specific effects of these epigenetic inhibitors and propose using them in a more selective and prudent manner.
Mon, 16 April 2018
ARTICLE Download: 190| View: 191| Comments: 0 | doi:10.20944/preprints201804.0199.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: ultrasound; strain elastography; quantification; strain ratio; strain quantification; measurement variability; pancreas; EUS; Crohn’s disease; carcinoma
Online: 16 April 2018 (08:56:58 CEST)
1) Background: Ultrasound-based strain imaging is now available in several ultrasound (US) scanners. Strain ratio (SR) can be used to quantify strain recorded simultaneously in two different user-selected areas, ideally exposed to the same amount of stress. The aim of this study was to evaluate SR variability when assessed in an in-vitro setup with a tissue-mimicking phantom, on resected tissue samples and in live tissue scanning with endoscopic applications. 2) Material and methods: Retrospective analysis of SR for quantification of elastic contrasts in a tissue-mimicking phantom containing four homogenous inclusions, in 38 resected bowel wall lesions and in 48 focal pancreatic lesions examined in vivo. Median SR and the inter-quartile range (IQR) was calculated on all external and endoscopic US-applications. The IQR/median provides a measure of the SR variability focusing on the two percentiles of the data closest to the median value. 3) Results: The overall variability of SR was lowest in a tissue-mimicking phantom (mean QR/median SR: 0.07). In resected bowel wall lesions representing adenomas, adenocarcinomas or Crohn lesions, the variability increased (mean IQR/Median: 0.62). During an endoscopic examination of focal pancreatic lesions in vivo, the variability increased further (mean IQR/Median: 2.04). 4) Conclusion: SR variability increased when assessed on different targets with growing heterogeneity and biological variability as one moved from homogeneous media to live tissues and endoscopic application. This may indicate a limitation for the accuracy SR evaluation in clinical applications.
Fri, 30 March 2018
ARTICLE Download: 252| View: 255| Comments: 0 | doi:10.20944/preprints201803.0258.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: afamin; adropin; alcoholic liver cirrhosis
Online: 30 March 2018 (06:21:07 CEST)
Introduction: Liver cirrhosis develops in about 10% of alcohol abusers. To date, a number of cells and cytokines have been identified, which are involved in induction of liver fibrotic processes. Nevertheless, the pathogenesis of liver cirrhosis has not been fully elucidated. The aim of the present study was to determine serum concentrations of afamin and adropin in patients with alcoholic liver cirrhosis and to define their correlation with the stage of disease. Materials and methods: The study included 99 patients with alcoholic cirrhosis from the region of Lublin, (Eastern Poland). Liver cirrhosis was diagnosed based on clinical features, history of heavy alcohol consumption, laboratory tests and abdominal ultrasonography. The control group consisted of 20 healthy individuals without liver disease who did not abuse alcohol. The serum afamin and adropin concentrations were determined using ELISA kits. Results: The concentration of afamin was found to be significantly lower in patients with compensated alcoholic liver cirrhosis, i.e. P-Ch B (85.1±40.6 μg/ml) and P-Ch C (56.4±32.3 μg/ml) individuals, as compared to the control group (135.9±43.6 μg/ml); p-value was <0.01 and <0.001, respectively. As far as adropin is concerned, a reverse relationship was demonstrated: the highest concentration was found in patients with P-Ch C (11.7±5.7 ng/ml) cirrhosis. Furthermore, the above concentration was significantly higher compared to patients with P-Ch A cirrhosis (7.2±2.8 ng/ml; p<0.05) and controls (7.5±2.6 ng/ml; p<0.05). Conclusions: The concentration of afamin decreases with the severity of alcoholic liver cirrhosis, which most likely results from impaired hepatic synthesis. Otherwise, the higher the stage of disease according to the Child-Pugh score, the higher the concentration of adropin.
Thu, 15 February 2018
REVIEW Download: 212| View: 207| Comments: 0 | doi:10.20944/preprints201802.0101.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Spleen; Islet Transplantation; Transplant site; Immunity; Tolerance; Regeneration; Diabetes mellitus; Liver; Intrasplenic; Stem cell
Online: 15 February 2018 (10:42:16 CET)
Islet transplantation is a cellular replacement therapy to treat severe diabetes mellitus, but its clinical outcome is unsatisfactory at present. One factor in clinical success of this therapy is selection of the most appropriate transplantation site. In this review, we review evidence showing the advantages of the spleen as a transplantation site for islets. The spleen has been studied for a long time as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity. Recently it has also been shown that the spleen contributes to the regeneration of transplanted islets and that splenic stem cells have the potential to differentiate into islet cells. The spleen also has some disadvantages associated with the transplantation procedure itself (bleeding, thrombosis and splenic infarction). The efficacy of transplantation is not as high as that obtained with intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established before the spleen can be effectively used in the clinic to support the engraftment of multiple transplanted islets.
Thu, 7 December 2017
REVIEW Download: 611| View: 352| Comments: 0 | doi:10.20944/preprints201712.0042.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: corticotropin releasing factor; irritable bowel syndrome (IBS); maternal separation (MS); neurotransmitters; pain; psychosocial stress; visceral hyperalgesia; water avoidance stress (WAS); wrap restrain stress (WRS)
Online: 7 December 2017 (07:39:49 CET)
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal diseases in humans. It is characterized by visceral pain and/or discomfort, hypersensitivity and abnormal motor responses along with change in gut habits. Although the etio-pathogenesis of IBS is only partially understood, a main role has been attributed to psychosocial stress of different origin. Animals models such as neonatal maternal separation, water avoidance stress and wrap restraint stress have been developed as psychosocial stressors in the attempt to reproduce the IBS symptomatology and identify the cellular mechanisms responsible for the disease. The study of these models has led to the production of drugs potentially useful for IBS treatment. This review intends to give an overview on the results obtained with the animal models; to emphasize the role of the enteric nervous system in IBS appearance and evolution and as a possible target of drug therapies.
Mon, 4 December 2017
REVIEW Download: 542| View: 450| Comments: 0 | doi:10.20944/preprints201712.0014.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: pancreatic cancer; immune surveillance; galectins; immunotherapy; immune checkpoints; stroma
Online: 4 December 2017 (05:17:15 CET)
Pancreatic ductal adenocarcinoma (PDA), the most frequent type of pancreatic cancer, is one of the main unfinished businesses in the biomedical and clinical fields, with still discouraging 5 year survival rates and poor therapy efficiency. PDA abundant desmoplasia has for long played the lead in the mechanisms involved in poor drug performance, being the main source of cytokines and chemokines orchestrating rapid and silent tumor progression and guilty of isolating tumor cells into a extense fibrotic reaction resulting in inefficient drug delivery. However, since immunotherapy was proclaimed the breakthrough of the year back to 2013, the focus in the stroma of pancreatic cancer has interestingly moved from activated fibroblasts to the immune compartment, trying to understand the immunosuppressive factors that play part in the strong immune evasion that characterizes PDA. PDA microenvironment is highly immune-suppressive, being basically composed of T regulatory cells (Tregs), tumor-associated macrophages (TAMs) and myeloid-derived suppressive cells (MDSCs), which boycott CD8+ T-cell duties in tumor recognition and clearance. Interestingly, preclinical data have highlighted the importance of this immune evasion as the source of resistance to single checkpoint immunotherapies and cancer vaccines and point at pathways inhibiting the immune attack as the key to solve the therapy puzzle. Here, we will discuss the molecular mechanisms involved in PDA immune escape as well as the state of the art of the PDA immunotherapy.
Tue, 14 November 2017
REVIEW Download: 2631| View: 438| Comments: 0 | doi:10.20944/preprints201711.0081.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Marfan; connective tissue disease; irritable bowel syndrome; hernia
Online: 14 November 2017 (04:08:45 CET)
Symptoms attributed to the gastrointestinal manifestations of multi-system disorders play an important role in the long-term management of these conditions. Gastrointestinal complications of a variety of connective tissue disorders have been studied and there is an increased interest in the incidence and prevalence of these symptoms. Descriptions of the occurrence of gastrointestinal complications in Marfan syndrome have appeared infrequently in the medical literature. In this review article we focus on both structural and functional gastrointestinal pathology that may occur in patients with Marfan syndrome.
Wed, 25 October 2017
REVIEW Download: 328| View: 330| Comments: 0 | doi:10.20944/preprints201710.0160.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: inflammasomes; ulcerative colitis; Crohn’s disease; interleukin (IL)-1β; IL-18
Online: 25 October 2017 (02:46:14 CEST)
Pattern recognition receptors such as nucleotide-binding oligomerization domain (NOD)-containing protein receptors (NLRs) and the pyrin and HIN domain (PYHIN) receptors initiate the inflammatory response following cell stress or pathogenic challenge. When activated some of these receptors oligomerize to form the structural backbone of a signalling platform known as the inflammasome. The inflammasome promotes the activation of caspase-1 and the maturation of the proinflammatory cytokines, interleukin (IL)-1β and IL-18. In the gut dysregulation of the inflammasome complex is thought to be a contributing factor in the development of inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD). The importance of inflammasomes to intestinal health has been emphasized by various inflammasome deficient mice in dextran sulphate sodium (DSS) models of intestinal inflammation and by the identification of novel potential candidate genes in population based human studies. In this review we summarise the most recent finding with regard to formation, sensing and regulation of the inflammasome complex and highlight their importance in maintaining intestinal health.
Fri, 14 July 2017
ARTICLE Download: 495| View: 487| Comments: 0 | doi:10.20944/preprints201707.0033.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: hepatic inflammation; high-fat-cholesterol diet; hypertension; mitogen-activated protein kinase; nonalcoholic steatohepatitis; nuclear factor erythroid 2-related factor 2 pathway; nuclear factor-kappa B; spontaneously hypertensive rat; stroke-prone spontaneously hypertensive5/Dmcr; Wistar Kyoto
Online: 14 July 2017 (10:54:38 CEST)
Populations with essential hypertension have a high risk of nonalcoholic steatohepatitis (NASH). In this study, we investigated the mechanism that underlies the progression of hypertension-associated NASH by comparing differences in the development of high fat and cholesterol (HFC) diet-induced NASH among three strains of rats, i.e., two hypertensive strains comprising spontaneously hypertensive rats and the stroke-prone spontaneously hypertensive 5/Dmcr, and the original Wistar Kyoto rats as the normotensive control. We investigated histopathological changes and molecular signals related to inflammation in the liver after feeding with the HFC diet for 8 weeks. The diet induced severe lobular inflammation and fibrosis in the livers of the hypertensive rats, whereas it only caused mild steatohepatitis in the normotensive rats. Increased activation of proinflammatory signaling (transforming growth factor-β1/mitogen-activated protein kinases pathway) was observed in the hypertensive strains fed with the HFC diet. In addition, the HFC diet suppressed the nuclear factor erythroid 2-related factor 2 pathway in the hypertensive rats and led to lower increases in the hepatic expression of heme oxygenase-1, which has anti-oxidative and anti-inflammatory activities. In conclusion, these signaling pathways might play crucial roles in the development of hypertension-associated NASH.
Wed, 3 May 2017
ARTICLE Download: 522| View: 752| Comments: 0 | doi:10.20944/preprints201704.0181.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: microparticles, biomarkers, hepatocellular carcinoma
Online: 3 May 2017 (09:53:22 CEST)
Circulating microparticles (MPs) are novel potential biomarkers in cancer patients. Their role in hepatocellular carcinoma (HCC) is under intensive investigation. In this study we tested the hypothesis that MPs expressing the antigen HepPar1 are increased in the blood of subjects with HCC and may serve as markers of early recurrence after liver resection (LR). We studied fifteen patients affected by HCC undergoing LR and used flow cytometry to assess the number of circulating HepPar1+ MPs. Ten subjects without HCC (five with liver cirrhosis and 5 with healthy liver) were used as controls. After LR, HCC patients were followed-up for early recurrence, which occurred in seven cases. The number of circulating HepPar1+ MPs was significantly higher in subjects affected by HCC, compared to individuals without cancer (p<0.01). We also found that, among HCC patients, the number of circulating HepPar1+ MPs, measured before LR, was significantly higher in those who displayed early recurrence compared to those without recurrence (p=0.02). Of note, other types of circulating MPs, such as those derived from endothelial cells (CD144+) or those produced by the activated endothelium (CD144+/CD62+) were not associated with HCC, neither could predict HCC recurrence. HepPar1+ MPs deserve further investigation as novel biomarkers of disease and prognosis in HCC patients.
Tue, 11 April 2017
ARTICLE Download: 624| View: 688| Comments: 0 | doi:10.20944/preprints201704.0062.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: survivin; high expression; gastrointestinal cancer; prognostic
Online: 11 April 2017 (10:51:06 CEST)
Previous studies on the prognostic impact of survivin expression in gastrointestinal (GI) cancer have yielded inconsistent results. This study was initiated to assess the relationship between survivin expression and overall survival (OS) or disease free survival (DFS) in GI cancer patients. We applied system literature searches on EMBASE, PubMed, Web of science, and the Cochrane library to conduct this up-to-date meta-analysis. Thirty studies with totally 3622 GI cancer patients were collected. The prevalence of high survivin expression in GI cancer was 0.57 (95% CI: 0.51-0.63). High survivin expression was significantly associated with shorter OS (HR 1.57, 95% CI: 1.42-1.74) and DFS (HR 1.38, 95% CI: 1.21-1.58). Subgroup analysis also showed significant association between high survivin expression and poorer OS or DFS in gastric cancer or colorectal cancer. In summary, our study indicated that high survivin expression was related to poor prognosis in GI cancer. Well-designed studies with large sample and more convincing data are needed to confirm our conclusion.
Mon, 27 March 2017
ARTICLE Download: 710| View: 717| Comments: 0 | doi:10.20944/preprints201703.0204.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: alcohol; liver cirrhosis; selenium; interleukin-6; growth differentiation factor-15
Online: 27 March 2017 (16:12:33 CEST)
According to some authors, the serum selenium level is strongly associated with the severity of liver diseases including liver cirrhosis. The aim of the study was to determine the relationship between the concentration of selenium and pro-inflammatory and profibrotic cytokines – interleukin-6 (IL-6) and growth differentiation factor 15 (GDF-15) in patients with alcoholic liver cirrhosis. The parameters studied were determined in serum of 99 alcoholic liver cirrhosis patients divided based on the severity of disease according to the Child-Turcotte-Pugh criteria. In patients with liver cirrhosis, the serum selenium concentration was statistically lower whereas serum IL-6 and GDF-15 concentrations were higher than those in the control group. Moreover, the concentration of selenium negatively correlated with the levels of GDF-15 and IL-6. The above results may indicate a role of selenium deficiency in the pathogenesis and progression of alcoholic liver disease.
Wed, 15 March 2017
REVIEW Download: 486| View: 563| Comments: 0 | doi:10.20944/preprints201703.0093.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: lifestyle factors; chronic inflammatory diseases; treatment result; treatment response; diet; meat intake; dietary pattern; food; mucosa associated bacteria; epithelium-associated bacteria; microbiome; fibre intake; personalized medicine; mucus; sulphate-reducing bacteria; mucin-degrading bacteria; Western style diet; anti-TNF
Online: 15 March 2017 (07:29:13 CET)
We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had no dietary restrictions (78% versus 67%, p = 0.51). A meta-analysis of 295 patients found higher odds of achieving clinical remission and remaining in clinical remission among patients on combination therapy with specialised enteral nutrition and Infliximab (IFX) compared with IFX monotherapy (OR 2.73; 95% CI: 1.73–4.31, p < 0.01, OR 2.93; 95% CI: 1.66–5.17, p < 0.01, respectively). In conclusion, evidence-based knowledge on impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in observational, animal and interventional studies are warranted.
Mon, 21 November 2016
ARTICLE Download: 1159| View: 958| Comments: 0 | doi:10.20944/preprints201611.0107.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: pancreatic cancer; deguelin; autophagy; doxorubicin
Online: 21 November 2016 (10:01:23 CET)
Pancreatic cancer is the fourth most common cause of cancer mortality worldwide. Furthermore, patients with pancreatic cancer experience limited benefit from current chemotherapeutic approaches because of drug resistance. Therefore, an effective therapeutic strategy for patients with pancreatic cancer is urgently required. Deguelin is a natural chemopreventive drug that exerts potent antiproliferative activity in solid tumors by inducing cell death. However, the molecular mechanisms underlying this activity have not been fully elucidated. Here we show that deguelin blocks autophagy and induces apoptosis in pancreatic cancer cells in vitro. Autophagy induced by doxorubicin plays a protective role in pancreatic cancer cells, and suppressing autophagy by chloroquine or silencing autophagy protein 5 enhanced doxorubicin-induced cell death. Similarly, inhibition of autophagy by deguelin also chemosensitized pancreatic cancer cell lines to doxorubicin. These findings suggest that deguelin has potent anticancer effects against pancreatic cancer and potentiates the anti-cancer effects of doxorubicin. These findings provide evidence that combined treatment with deguelin and doxorubicin represents an effective strategy for treating pancreatic cancer.