World Journal of Gastrointestinal Pharmacology and Therapeutics最新文献

Background: Constipation as a most common non-motor symptom of Parkinson's disease (PD), has a higher prevalence compared to the general population. The etiologies of constipation in PD are diverse. In addition to physical weakness and other factors of disease, the lifestyles and eating habits are also important factors. Therefore, the prevalence and influencing factors of constipation may vary among different populations.

Aim: To determine the prevalence of constipation and analyze relative factors in a cohort of Chinese patients with PD.

Methods: All the patients diagnosed with PD according to the movement disorders society criteria were consecutively collected by a self-developed questionnaire. Rome III diagnostic criteria were used to assess functional constipation and Wexner score was used to estimate the severity of constipation. Non-motor symptoms (NMS) were assessed with the non-motor symptoms assessment scale (NMSS). Unified Parkinson's disease Rating Scale III (UPDRS III) was used to evaluate the severity of motor symptoms. The modified Hoehn-Yahr stage was used to evaluate the severity of PD. Cognitive function was assessed using Montreal cognitive assessment (MoCA). Depression and anxiety were rated with the Hamilton depression scale (HAMD) and the Hamilton anxiety scale (HAMA). Quality of life was assessed using the Parkinson's disease Questionnaire-39 items (PDQ-39).

Results: Of 166 patients enrolled, 87 (52.41%) were accompanied with constipation, and 30 (34.48%) experienced constipation for 6.30 ± 5.06 years before motor symptoms occurred. Age, Hoehn-Yahr stage, disease duration, levodopa medication times, incidence of motor complications, the scores of UPDRS total, UPDRS III, NMSS, HAMD, HAMA, and PDQ-39 in the constipation group were higher than those in the non-constipation group (P < 0.05), but there was no difference in the scores of MoCA, clinical types, or medications between the two groups (P > 0.05). There was a higher incidence of depression in patients with constipation (P < 0.05), but there were no difference in the incidence of anxiety and cognitive impairment between the two groups (P > 0.05). As Hoehn-Yahr stages increased, the severity of constipation increased (P < 0.05), but not the incidence of constipation (P > 0.05). Pearson correlation analysis showed that constipation was moderately positively correlated with age, Hoehn-Yahr stage, and scores of NMSS, UPDRS III, UPDRS total, PDQ-39, HAMD, and HAMA (r = 0.255, 0.172, 0.361, 0.194, 0.221, 0.237, 0.238, and 0.207, P < 0.05). Logistic regression analysis showed that only NMSS score was an independent risk factor for constipation (P < 0.001).

Conclusion: Our findings confirm that constipation has a relatively high frequency in patients with PD. PD patients with constipation have a higher inc

Background: Irritable bowel syndrome (IBS) is a bowel disorder involving abdominal pain or discomfort along with irregularity of stool form and passage frequency. The pathophysiology is poorly understood and seems to be multifactorial. Investigations of possible causes of IBS have included only a few colonic transit studies and no simultaneous determination of the colonic faecal content.

Aim: To compare colon transit time and faecal load between IBS-patients and healthy control subjects.

Methods: The study included 140 patients with IBS, with a mean age of 50.0 years. The control group comprised 44 healthy persons with a mean age of 43.4 years, who were selected at random from the National Civil Register. Both the patient group and the control group underwent a marker study to measure colon transit time (CTT) and to calculate a faecal loading score. The patient group underwent treatment with a combined prokinetic regime, after which their CTT and faecal loading were reassessed. Analyses were performed to compare measurements between the control group and the patient group before and after treatment.

Results: Compared to healthy controls, IBS-patients exhibited a significantly prolonged mean CTT (45.48 h vs 24.75 h, P = 0.0002) and significantly greater mean faecal loading scores in all colonic segments (P < 0.001). Among IBS patients, we found no significant differences between the 48 h and 96 h radiographs. Among patients exhibiting increased CTT and faecal loading, approximately half exhibited a palpable mass in the right iliac fossa. After intervention with a prokinetic treatment, the mean CTT among IBS patients was reduced from 45.48 h to 34.50 h (P = 0.091), with the post-treatment CTT not significantly differing from the CTT among control subjects (P = 0.095). The faecal loading score among IBS patients did not significantly differ before and after treatment (P = 0.442). The post-treatment faecal loading score in IBS patients remained significantly higher compared to that in controls (5.3 vs 4.3, P = 0.014). After treatment, half of the IBS-patients were relieved of bloating, while the majority no longer experienced abdominal pain and achieved a daily consistent stool.

Conclusion: IBS-patients exhibited prolonged CTT and heavier faecal loading. These assessments may aid in diagnosis. Faecal retention may contribute to IBS symptoms, which can be treated using a prokinetic regime.

Background: TreXTAM^® is a combination of the key regulatory cytokine transforming growth factor beta (TGFβ) and all trans retinoic acid (ATRA) microencapsulated for oral delivery to immune structures of the gut. It is in development as a novel treatment for inflammatory bowel disease (IBD).

Aim: To measure TGFβ levels in blood and tissue after oral administration of encapsulated TGFβ.

Methods: Animals were orally administered encapsulated TGFβ by gavage. Levels of drug substance in blood and in gut tissues at various times after administration were measured by ELISA.

Results: We made the surprising discovery that oral administration of TreXTAM dramatically (approximately 50%) and significantly (P = 0.025) reduced TGFβ levels in colon, but not small intestine or mesenteric lymph nodes. Similarly, levels in rat serum after 25 d of thrice weekly dosing with either TreXTAM, or microencapsulated TGFβ alone (denoted as TPX6001) were significantly (P < 0.01) reduced from baseline levels. When tested in the SCID mouse CD4+CD25- adoptive cell transfer (ACT) model of IBD, oral TPX6001 alone provided only a transient benefit in terms of reduced weight loss.

Conclusion: These observations suggest a negative feedback mechanism in the gut whereby local delivery of TGFβ results in reduced local and systemic levels of the active form of TGFβ. Our findings suggest potential clinical implications for use of encapsulated TGFβ, perhaps in the context of IBD and/or other instances of fibrosis and/or pathological TGFβ signaling.

Background: After parietal peritoneum excision with an underlying superficial layer of muscle tissue in rats, there is failed vasculature, and finally, increased adhesion formation. We hypothesized that unlike nitric oxide (NO)-agents, L-NAME and/or L-arginine, the application of the stable gastric pentadecapeptide BPC 157 with its most recent vascular effects ("vascular recruitment") means attenuated bowel adhesion formation and NO- and malondialdehyde (MDA)-tissue values.

Aim: To focused on the bowel adhesion and the therapy with the BPC 157, its most and application of NO-agents.

Methods: Along with defect creation, medication was (1) during surgery, once, at 1 min after defect creation as an abdominal bath (1 mL/rat), BPC 157 (10 µg/kg, 10 ng/kg, 1 mL/rat), an equivolume of saline, L-NAME (5 mg/kg), L-arginine (200 mg/kg) alone and/or combined. Alternatively, medication was (2) intraperitoneally once daily, first application at 30 min after surgery, last application 24 h before assessment at d 7 or d 14. As a postponed therapy to pre-existing adhesion (3), BPC 157 (10 µg/kg, 10 ng/kg intraperitoneally, 1 mL/rat) was given once daily since d 7.

Results: The recovery effect of the BPC 157 regimens goes with the presence of abundant vascular vessels in and near the defect, which occurs rapidly. Lastly, also applied as post-treatment, BPC 157 creates attenuated adhesions, minimal or no adhesion. Contrarily, NO-agents have diverse initial and final effects: The initial weakening of blood vessel disappearance and finally, severe worsening of adhesions (L-NAME) vs the initial weakening of blood vessel disappearance and finally, attenuation of adhesions formation (L-arginine), which counteract each other response given together. Importantly, BPC 157 maintains its beneficial effect also when given with NO-agents (L-NAME + BC 157; L-arginine + BPC 157; L-NAME + L-arginine + BPC 157). Finally, with respect to the increased NO- and MDA- values-adhesion tissue formation relation, unlike diverse effect of the NO-agents, the BPC 157 application effect regularly combines decrease on the increased NO- and MDA- values and the beneficial outcome (less adhesion formation).

Conclusion: BPC 157 therapy can be suited for the realization of the peritoneal defect healing with minimal or no adhesion formation.

Background: Advanced gastric cancer (GC) with liver metastasis is often characterized by multiple and bilobular metastases and may also be associated with extrahepatic metastatic lesions. Hence, many physicians consider that radical surgeries are contraindicated for liver metastases from GC (LMGC). According to the 2017 Japanese treatment guideline for GC, a smaller number of liver metastases without unresectable factors may be an indication for liver resection (LR) with curability. The actual 5-year overall survival (OS) rate ranges from 0 to 0.37.

Aim: To present the institutional indications for LR for LMGC and identify important factors for prognostic outcomes.

Methods: In total, 30 patients underwent LR for LMGC during a 14-year period, and we evaluated the clinical, surgical, and oncological findings. In all patients, radical surgery with intentional lymphadenectomy was performed for the primary GC. The median follow-up duration after the initial LR was 33.7 mo, and three patients with no recurrence died of causes unrelated to the LMGC. The OS and recurrence-free survival rates after the initial LR were assessed.

Results: Seventeen patients had metachronous LMGC. The initial LR achieved curability in 29 patients. Perioperative chemotherapy was introduced in 23 patients. The median greatest LMGC dimension was 30 mm, and the median number of LMGC was two. Twenty-two patients had unilobular LMGC. The 5-year OS and recurrence-free survival rates were 0.48 and 0.28, respectively. The median survival duration and recurrence-free duration after the initial LR were 16.8 and 8.6 mo, respectively. Twenty-one patients developed recurrence after the initial LR. Additional surgeries for recurrence were performed in nine patients, and these surgeries clearly prolonged the patients' survival. Pathological serosal invasion was an independent predictor of a poor prognostic outcome after the initial LR. Aggressive LR may be indicated for carefully selected patients with LMGC.

Conclusion: Our results of LR for LMGC seem acceptable. Additional surgeries for recurrence after the initial LR might prolong OS. Pathological serosal invasion is important for poor prognostic outcomes.

Background: The existence of genetic anticipation has been long disputed in inflammatory bowel disease (IBD) in the absence of the explanatory mechanism.

Aim: To determine whether it was predictive of genetic anticipation, we evaluated telomere length in IBD. We hypothesized that multiplex IBD families exhibit a genetic defect impacting telomere maintenance mechanisms.

Methods: We studied three IBD families with multiple affected members in three successive generations. We determined telomere length (TL) in lymphocytes and granulocytes from peripheral blood of the affected members using flow cytometry and fluorescence in-situ hybridization (flow FISH). We also performed whole exome sequencing in the blood of all available family members and used PhenoDB to identify potential candidate gene variants with recessive or dominant modes of inheritance.

Results: Out of twenty-four patients of European descent selected to participate in the study, eleven patients, eight parent-child pairs affected by IBD, were included in the genetic anticipation analysis. Median difference in age at diagnosis between two successive generations was 16.5 years, with earlier age at onset in the younger generations. In most of the affected members, the disease harbored similar gastrointestinal and extraintestinal involvement but was more aggressive among the younger generations. TL was not associated with earlier age at onset or more severe disease in members of successive generations affected by IBD. NOD2 gene mutations were present in the Crohn's disease patients of one family. However, no gene variants were identified as potential candidates for inheritance.

Conclusion: Telomere shortening appears unlikely to be involved in mechanisms of possible genetic anticipation in IBD. Further studies using a larger sample size are required to confirm or refute our findings.

Background: There has been a worldwide increase in the reported incidence of inflammatory bowel disease (IBD) in children over the past 2-3 decades. The hepatobiliary (HB) manifestations of IBD have been well-studied in children in industrialized and developed countries but are infrequently reported in low- and middle-income countries (LMIC) such as Egypt.

Aim: To determine the prevalence of the HB manifestations in a cohort of Egyptian children with IBD.

Methods: This cross-sectional observational study was carried out over a period of 6 mo (between June 2013 to December 2013) at the Paediatric Hepatology and Gastroenterology Units of Cairo University Children's Hospital, which is the largest paediatric tertiary care centre in the country.

Results: The study included 48 patients with confirmed IBD based upon clinical, laboratory, endoscopic and histopathological features, 29 (60.4%) were male. Twenty-four patients (50%) had ulcerative colitis (UC), 11 (22.9%) had Crohn's disease (CD) and 13 (27.1%) had unclassified-IBD (IBD-U), which was formerly known as indeterminate colitis. The mean age of the patients at the time of presentation was 8.14 (± SD 4.02) years and the mean age at the time of study enrolment was 10.16 (± SD 4.19) years. All patients were screened for HB manifestations by physical examination, liver function tests, imaging and liver biopsy when indicated. HB disorders were confirmed in 13 patients (27.1%). Transaminases were elevated in 3 patients (6.3%). Two patients (4.2%) had elevated biliary enzymes (one was diagnosed as primary sclerosing cholangitis (PSC) and the other was diagnosed with PSC/autoimmune hepatitis overlap syndrome and the third patient had hepatitis C virus infection. Ten patients (20.8%) had bright echogenic liver on ultrasound suggesting fatty infiltration as a sequel of malnutrition or medication toxicity.

Conclusion: The commonest HB disorders in Egyptian children with IBD were abnormal liver function tests, fatty infiltration and PSC. These HB manifestations in paediatric patients in LMIC may be relatively more common than in industrialized countries. Therefore, IBD patients in LMIC should be meticulously screened for liver disease to allow prompt diagnosis and management.

Background: Malnutrition affects 40%-90% of patients with cirrhosis of the liver. L3 skeletal muscle index (L3SMI) is presently accepted as the most objective and quantitative measure available for sarcopenia, a surrogate marker of malnutrition. L3SMI application is, however, limited by non-availability of computed tomography scanning in remote areas, cost, need for extensive training, and the risk of exposure to radiation. Therefore, an alternative dependable measure with wider availability is needed. Malnutrition causes sarcopenia not only in skeletal muscles but also in other muscular structures such as the psoas muscle, diaphragm and tongue. We therefore hypothesised that the tongue, being easily accessible for inspection and for measurement of thickness using ultrasonography, may be used to document sarcopenia.

Aim: To measure and compare tongue thickness in healthy individuals and in patients with cirrhosis of the liver and to study its correlation with conventional prognostic scores for patients with cirrhosis of the liver.

Methods: Tongue thickness was measured using ultrasonography. One hundred twenty subjects of either gender aged 18 to 65 years were studied, with 30 subjects in each group. The tongue thickness was compared between groups based on "Child Turcotte Pugh" (CTP) scores. The correlations between measured tongue thickness and "Model for end stage liver disease" (MELD) score and between age and measured tongue thickness were also assessed.

Results: Mean tongue thickness (mean ± SD) in patients with CTP class A, B and C was 4.39 ± 0.39 cm, 4.19 ± 0.53 cm, and 3.87 ± 0.42, respectively, and was 4.33 ± 0.49 cm in normal healthy individuals. Significant differences were seen in tongue thickness between patients with CTP class C and those with CTP class A and B (P < 0.05). Patients with CTP class C also had a significantly reduced tongue thickness than normal individuals (P < 0.05). However, no significant difference was seen in tongue thickness between patients with CTP class A and B and normal individuals. A statistically significant, negative correlation was found between MELD score and tongue thickness (r = -0.331) (P < 0.001). No correlation was observed between L3SMI and MELD score (r = 0.074, P = 0.424). L3SMI (mean ± SD) in healthy subjects was 39.66 ± 6.8 and was 38.26 ± 8.88 in patients with CTP class C, and the difference was not significant. No significant correlation was found between age of the patients and tongue thickness. Intra-class correlation coefficient was used to determine the reliability of the tongue thickness measurements. The intra-class correlation coefficient was 0.984 (95%CI: 0.979-0.989) and was indicative of good reliability.

Conclusion: Tongue thickness measured by ultrasonography, correlates significantly with the severity of liver disease, as ass

Background: Neovascularisation is common to a variety of gastrointestinal (GI) disorders with differing aetiologies and presentations; usually affecting adults above 60 years. Shared angiogenic factors modulated by disease specific elements could be a common denominator and represent novel diagnostic and therapeutic targets. As yet, assessment of angiogenic factors across several GI vascular disorders associated with recurrent bleeding and anaemia has not been reported.

Aim: To assess serum levels of angiogenic factors in several intestinal vascular disorders.

Methods: A case control study was performed in Tallaght University Hospital in patients with endoscopically proven small bowel angiodysplasia (SBA), portal hypertensive gastropathy (PHG), gastric antral vascular ectasia (GAVE) and non-bleeding, non-anaemic controls. Using enzyme-linked immunosorbent assay, concentrations of Angiopoietin 1 (Ang-1), Ang-2 and vascular endothelial growth factor (VEGF) were measured from 2 serum tubes of blood following informed consent. The relative expression of Ang-1 and Ang-2 and Ang-1/2 ratio was calculated and compared between groups. Statistical analysis was applied using a t-test, and a P value of < 0.05 was considered significant.

Results: To date 44 samples were tested: 10 SBA, 11 PHG, 8 GAVE and 15 controls. Mean age 60 (range 20-85) years and 20 (45%) were males. Controls were significantly younger (49 years vs 66 years, P = 0.0005). There was no difference in VEGF levels between the groups (P = 0.6). SBA, PHG and GAVE Ang-1 levels were similar and were significantly lower than controls, (P = 0.0002, 95%CI: 241 to 701). Ang-2 levels were statistically higher in PHG and GAVE groups compared to controls (P = 0.01, 95%CI: 77.8 to 668) and as a result, also had a lower Ang-1/2 ratios compared to controls. While SBA Ang-2 levels were higher than controls, this did not reach statistical significance. Neither age nor haemoglobin level, which was similar between disease groups, could explain the difference. In addition, the median Ang-1/Ang-2 ratio for all patients was found to be significantly lower compared to controls, 8 vs 28 respectively, P = 0.001, 95%CI: -27.55 to -7.12.

Conclusion: Our novel pilot study suggests common alterations in Ang-1 and Ang-2 levels across several GI vascular disorders. Differences in Ang-1/Ang-2 ratios among vascular disorders compared to controls suggest disease-specific modulation.

Gastric outlet obstruction (GOO) is a medical condition characterized by epigastric pain and postprandial vomiting due to mechanical obstruction. The obstructions typically involved in GOO can be benign or malignant. Peptic ulcer disease is the most common cause of benign GOO, and malignant causes include gastric cancer, lymphoma, and gastrointestinal stromal tumor. With the eradication of Helicobacter pylori (H. pylori) and the use of proton pump inhibitors, the predominant causes have changed from benign to malignant diseases. Treatment of GOO depends on the underlying cause: Proton pump inhibitors, H. pylori eradication, endoscopic treatments including balloon dilatation or the placement of self-expandable stents, or surgery.