Search

Background. The superior mesenteric artery (SMA) syndrome is a rare entity presenting with upper gastrointestinal tract obstruction and weight loss. Studies to determine the optimal methods of diagnosis and treatment are required. Aims and Methods. This study aims at analyzing the clinical presentation, diagnosis, and management of SMA syndrome. Ten cases of SMA syndrome out of 2074 esophagogastroduodenoscopies were suspected. A contrast-enhanced computed tomography (CECT) scan was performed to confirm the diagnosis. After, a gastroenterologist and a nutritionist personalized the therapy. Furthermore, we compared the demographical, clinical, endoscopic, and radiological parameters of these cases with a control group consisting of 10 cases out of 2380 EGDS of initially suspected (but not radiologically confirmed) SMA over a follow-up 2-year period (2015-2016). Results. The prevalence of SMA syndrome was 0.005%. Median age and body mass index were 23.5 years and 21.5 kg/m2, respectively. Symptoms developed between 6 and 24 months. Median aortomesenteric angle and aorta-SMA distance were 22 and 6 mm, respectively. All patients improved on conservative treatment. In our series, a marked (>5 kg) weight loss (p=0.006) and a long-standing presentation (more than six months in 80% of patients) (p=0.002) are significantly related to a diagnosis of confirmed SMA syndrome at CECT after an endoscopic suspicion. A “resembling postprandial distress syndrome dyspepsia” presentation may be helpful to the endoscopist in suspecting a latent SMA syndrome (p=0.02). The narrowing of both the aortomesenteric angle (p=0.001) and the aortomesenteric distance (p<0.001) was significantly associated with the diagnosis of SMA after an endoscopic suspicion; however, the narrowing of the aortomesenteric distance seemed to be more accurate, rather than the narrowing of the aortomesenteric angle. Conclusion. SMA syndrome represents a diagnostic and therapeutic challenge. Our results show the following findings: the importance of the endoscopic suspicion of SMA syndrome; the preponderance of a long-standing and chronic onset; a female preponderance; the importance of the nutritional counseling for the treatment; no need of surgical intervention; and better diagnostic accuracy of the narrowing of the aorta-SMA distance. Larger prospective studies are needed to clarify the best diagnosis and management of the SMA syndrome.

Summary The translation initiation repressor 4E-BP2 is deamidated in the brain on asparagines N99/N102 during early postnatal brain development. This post-translational modification enhances 4E-BP2 association with Raptor, a central component of mTORC1 and alters the kinetics of excitatory synaptic transmission. We show that 4E-BP2 deamidation is neuron specific, occurs in the human brain, and changes 4E-BP2 subcellular localization, but not its disordered structure state. We demonstrate that deamidated 4E-BP2 is ubiquitinated more and degrades faster than the unmodified protein. We find that enhanced deamidated 4E-BP2 degradation is dependent on Raptor binding, concomitant with increased association with a Raptor-CUL4B E3 ubiquitin ligase complex. Deamidated 4E-BP2 stability is promoted by inhibiting mTORC1 or glutamate receptors. We further demonstrate that deamidated 4E-BP2 regulates the translation of a distinct pool of mRNAs linked to cerebral development, mitochondria, and NF-κB activity, and thus may be crucial for postnatal brain development in neurodevelopmental disorders, such as ASD., Graphical Abstract, Highlights • Deamidated 4E-BP2 occurs in neurons and is susceptible to ubiquitination/degradation • mTORC1 or glutamate receptor inhibition stabilizes deamidated 4E-BP2 • A Raptor-CUL4B ubiquitin ligase complex binds to deamidated 4E-BP2 • Deamidated 4E-BP2 regulates postnatal brain translation and NF-κB activity, Kouloulia et al. demonstrate that, during early postnatal brain development, deamidation of the translation initiation factor 4E-BP2 renders it susceptible to ubiquitination and proteasomal degradation via enhanced binding to the Raptor-CUL4B complex. mTORC1 or glutamate receptor inhibition stabilizes deamidated 4E-BP2. Moreover, deamidated 4E-BP2 regulates the translation of specific mRNAs and NF-κB activity.

The translation initiation repressor 4E-BP2 is deamidated in brain on asparagines N99/N102 during early postnatal brain development. This post-translational modification enhances 4E-BP2 association with Raptor, a central component of mTORC1 and alters the kinetics of excitatory synaptic transmission. We show that 4E-BP2 deamidation is neuron-specific, occurs in human brain and changes 4E-BP2 subcellular localisation, but not its disordered structure state. We demonstrate that deamidated 4E-BP2 is ubiquitinated more and degrades faster than the unmodified protein. We find that enhanced deamidated 4E-BP2 degradation is dependent on Raptor binding, concomitant with increased association with a Raptor-CUL4B E3 ubiquitin ligase complex. Deamidated 4E-BP2 stability is promoted by inhibiting mTORC1 or AMPARs, but not NMDARs. We further demonstrate that deamidated 4E-BP2 regulates the translation of a distinct pool of mRNAs linked to cerebral development, mitochondria and NF-κB activity, and thus may be crucial for postnatal brain development in neurodevelopmental disorders, such as ASD.

Irritable bowel syndrome (IBS) is a chronic, recurring, and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain, distention, and changes in bowel habits. Although there are several drugs for IBS, effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed. Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism, neurohormonal regulation, immune, dysfunction, the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS. With regards to therapies for restoring intestinal permeability, multiple studies with prebiotics and probiotics are ongoing, even if to date their efficacy has been limited. In parallel, much progress has been made in targeting low-grade inflammation, especially through the introduction of drugs such as mesalazine and rifaximin, even if a better knowledge of the mechanisms underlying the low-grade inflammation in IBS may allow the design of clinical trials that test the efficacy and safety of such drugs. This literature review aims to summarize the findings related to new and investigational therapeutic agents for IBS, most recently developed in preclinical as well as Phase 1 and Phase 2 clinical studies.

Zollinger-Ellison syndrome is an often progressive, persistent and frequently life-threatening disease, described for the first time as characterized by ulceration of the upper jejunum, hypersecretion of gastric acid and non-beta islet cell tumors of the pancreas; this syndrome is due to the hypersecretion of gastrin. We report a case of Zollinger-Ellison syndrome presenting as severe esophagitis evolving in stenosis, which demonstrates how a delayed diagnosis may induce risk of disease spreading. In this setting new diagnostic approaches, such as somatostatin receptor scanning and positron emission tomography with 68 Ga-labeled octreotide, could be particularly useful, as well as further new therapeutic options, such as molecular targeted treatments and peptide receptor radionuclide therapy, though surgery is currently the only form of curative treatment, and the role of the therapeutic options mentioned needs to be clarified by forthcoming studies

Low-grade intestinal inflammation plays a key role in the pathophysiology of irritable bowel syndrome (IBS), and this role is likely to be multifactorial. The aim of this review was to summarize the evidence on the spectrum of mucosal inflammation in IBS, highlighting the relationship of this inflammation to the pathophysiology of IBS and its connection to clinical practice. We carried out a bibliographic search in Medline and the Cochrane Library for the period of January 1966 to December 2014, focusing on publications describing an interaction between inflammation and IBS. Several evidences demonstrate microscopic and molecular abnormalities in IBS patients. Understanding the mechanisms underlying low-grade inflammation in IBS may help to design clinical trials to test the efficacy and safety of drugs that target this pathophysiologic mechanism.

Pneumatic dilatation (PD) and Surgical Miotomy (SM) are presently the best treatments for untreated achalasia, with similar efficacy. There is no information on the relative efficacy of PD in younger compared to older patients. Aim of our study was to compare success rate and safety of PD in patients under fifty years old and in those over fifty years old affected by achalasia. Twenty consecutive symptomatic patients were treated in our Unit with graded PD under fluoroscopic view. Five male and 15 female with a median age of 47 years were treated. Twelve patients were less than fifty years old (group I) while 8 were older (group II). Median dysphagia questionnaire score was 14 and13 ingroup I and II respectively. Technical success was achieved in all patients. Seven patients were previously treated through other techniques. In group I all patients achieved a complete remission of symptoms with significant decrease of the dysphagia questionnaire score (3). In group II all patients achieved a complete remission of symptoms with significant decrease of the dysphagia questionnaire score (4.5) but 3 of them repeated the procedure. In boths groups the efficacy of the dilation was radiologically confirmed. Neither early nor late complication were reported in either groups. In our experience PD was an effective and safe procedure both in young and old patients although the older group had more recurrences, all successfully re-dilated.

Background: self-expandable metallic stents (SEMS) are employed as the preferred non surgical palliative treatment for gastric outlet obstruction due to malignancies. Metallic stents are often employed to treat malignant anastomotic obstructions after surgicsl interventions as esophagojejunostomy, gastrojejunostomy and esophagogastrojejunostomy. Methods: this case series reports prospectively the clinical outcomes of SEMS in the palliative care of malignant anastomotic strictures caused by the recurrence gastric cancer follwing gastric surgery as oncological curative treatment, in a series of nine consecutive patients, treated between January 2009 and december 2012 in our center. Results: Nine patients (M:F=8:1) were enrolled in the study. The operation was a total gastrectomy with esophagogastrojejunostomy (n=4), subtotal gastrectomy with Bilroth-II reconstruction (n=4), subtotal gastrectomy with Billroth-II reconstruction (n=3), and subtotal gastrectomy with esophagogastrostomy (n=2). The technical success rate was 88,9%, and the clinical success rate was 88.9%. The reostruction of the stent, due to the ingrowth of the tumor, occurred in 1 patient (11,1%) within 1 month after stent placement. the migration of the stent occurred after the placement of a covered stent in 1 patient who underwent a subtotal gastrectomy (with Billroth-II reconstruction). A case o partial stent dislodgement was treated with the placement of a second stent. The median survival period was 180 days (range, 30-240 days) and the median stent patency was 45 days 8range, 30-90 days). Conclusions: Although the number of the patients treated with SEMS results, in this series, almost small to certainly judge the safety and feasibility of SEMS, we believe that the endoscopic insertion of SEMS seems to be a safe, easily feasible, and effective treatment in the palliative care of malignant anastomotic strictures caused by the recurrence of gastric cancer following gastric surgery. The technical and clinical success, and the onset of complications of this procedure are influenced by several factors, such as the type of anastomosis, the technical features of the stent, and the extent of the underlying tumor.

An association between multiple sclerosis and autoimmune hepatitis has been described. The latter can also be unmasked or exacerbated by a variety of therapies used in multiple sclerosis, such as beta-Interferon or glatiramer acetate. Two cases of hepatitis occurring after exposure to glatiramer acetate are described here: the first, was possibly due to autoimmune hepatitis, rather than glatiramer acetate induced liver injury, the second was definite autoimmune hepatitis. Both occurred in patients who had already experienced hepatitis exacerbations during previous beta-Interferon treatment. We suggest that glatiramer acetate can unmask hepatitis. Thus, liver enzyme monitoring should be undertaken frequently in those patients with multiple sclerosis receiving glatiramer acetate, with a history of hepatitis during treatment with Interferon beta-1a.

Twenty-four 12-week-old female turkeys divided into four equal groups were fed a basal diet (CONT) or basal diet supplemented with 300 mg α-tocopheryl acetate/kg (TOC), or 5 g rosemary/kg (ROS5), or 10 g rosemary/kg (ROS10), for 4 weeks. Following slaughter, fillets from breast were stored at 4 °C in the dark for 12 days, and lipid oxidation was assessed on the basis of the malondialdehyde formed, whereas microbial growth on the basis of total viable counts (TVC), lactic acid bacteria (LAB), Enterobacteriaceae (ENB) and psychrotrophic (PSY) bacteria. Results showed that incorporation of dried rosemary in turkey diets delayed lipid oxidation in raw breast meat during refrigerated storage. Dietary rosemary at the level of 1 g/100 g was significantly ( P 0.05 ) more effective in delaying lipid oxidation compared to 0.5 g/100 g but inferior to the dietary supplementation of 300 mg α-tocopheryl acetate/kg. TVC, LAB, ENB and PSY bacterial counts were all significantly increased ( P 0.05 ) in breast samples of all groups throughout the refrigerated storage. The TOC and CONT groups presented TVC, LAB, ENB and PSY counts that did not differ ( P > 0.05 ) among each other, during the whole storage period. However, the rosemary-supplemented groups presented bacterial counts that were significantly lower ( P 0.05 ) than the CONT and TOC groups, at day 2 of storage period and thereafter. During this period, the ROS5 group presented TVC, LAB, ENB and PSY counts that were significantly higher ( P 0.05 ) than the ROS10 group.

The aim of this work was to determine the chemical composition and microbiological quality of Mediterranean horse mackerel ( Trachurus mediterraneus ) muscle during the year and the consequent advantages or disadvantages in processing the raw material. A total of 180 samples were examined (15 samples per month) during two years (November 2001–November 2003). Fish were caught in the coastal waters of Chalkidiki peninsula (Northern Greece). Proximate composition of the muscle during the year resulted in: water 76.8 ± 1.39%, proteins 20.3 ± 0.68%, fat 1.3 ± 1.08% and ash 1.5 ± 0.08%. In March, April and May an increase in fat content of the muscle (2.5%, 2.8% and 2.1%, respectively) and a decrease in water content of the muscle (below 75.9%) were observed. On the contrary, fat content showed a decrease in September and October (0.4% and 0.6%, respectively), while water content of the muscle increased during these months (78.2% and 77.6%, respectively). The protein content of the muscle remained at high values, while the ash content was almost constant during the year. The mean value of muscle pH was 6.38 ± 0.16; extreme values ( 7) of muscle pH were not observed. Total Viable Bacteria, Shewanella putrefaciens and Pseudomonas spp. were used as microbial indices to evaluate the microbiological quality of the muscle. Mean counts of Total Viable Bacteria, S. putrefaciens and Pseudomonas spp. during the year were: 4.01 ± 0.38 log 10 cfu/g, 2.37 ± 0.43 log 10 cfu/g and 3.34 ± 0.27 log 10 cfu/g, respectively. The variations of the values within seasons are minimal and significant homogeneity in the chemical composition and microbiological quality of Mediterranean horse mackerel muscle is observed. This is an important advantage in processing of the raw material.