Going to Where No One Went Before: Endoscopic Procedures of the Small Bowel

__Abstract__ Diagnostic and therapeutic endoscopic procedures of the small-bowel have for a long time been a great challenge to gastroenterologists. Especially the anatomy of the small intestine in combination with the lack of adequate, non-invasive, diagnostic tools, made it an almost ‘no-go’zone. Only in selected cases push enteroscopy and intraoperative enteroscopy were performed. Push enteroscopy has both diagnostic and therapeutic capabilities, but typically only examines a limited part of the proximal small bowel. Intraoperative enteroscopy permits examination of the entire small bowel and therapeutic interventions, but is much more invasive. The need for endoscopic access to improve diagnosis and treatment of small bowel disease has led to the development of novel endoscopic technologies. In 2000 the diagnostic and non-invasive video capsule endoscopy was introduced, followed by the more invasive double-balloon enteroscopy system in 2001, the latter combining diagnostic and therapeutic capabilities. The following years, single balloon enteroscopy and spiral enteroscopy were introduced as alternatives for double balloon enteroscopy, with in theory, comparable diagnostic and therapeutic capabilities. Complete enteroscopy of the small bowel is now in reach: ‘easy’ and much less invasive, and can be performed world wide in any endoscopy unit

Therapeutic balloon-assisted enteroscopy

Since the introduction of the first balloon-based enteroscopic technique in 2001, therapeutic balloon-assisted enteroscopy (BAE) using either the single or double balloon enteroscopy technique (respectively SBE and DBE) has evolved rapidly. Argon plasma coagulation (APC), polypectomy, dilation therapy of strictures, and therapy of the pancreatico-biliary system in patients with surgical altered proximal intestinal anatomy: all have been successfully introduced to treat pathological findings in all segments of the small bowel. The clinical impact of treatment of vascular malformations, strictures caused by chronic inflammation (especially Crohn's disease) and polypectomy therapy (especially in the Peutz-Jeghers syndrome) seems evident. The decrease of, often repeated, surgical therapy after successful therapeutic BAE in the latter 2 patient groups appears to be a big step forward in treatment. The development of newer enteroscopes, specialized equipment and improved sedation of patients adds positively to the clinical management of undergoing therapeutic BAE. The overall complication rate of therapeutic BAE seems acceptable, but is higher compared to therapeutic colonoscopy which needs further attention in future

Effects of saliva and nasal secretion on some physical properties of four different resin materials

Objective: Aim of this study was to evaluate possible effects of saliva and nasal secretion on some physical properties, such as sorption, solubility, surface hardness and colour change on four different resin-based materials over a certain time period. Materials and Methods: A total of 128 disc-shaped specimens with a diameter of 50mm and thickness of 0.5mm were tested to evaluate sorption and solubility (ISO-1567). The specimens were stored in different solutions prior to testing. Surface hardness measurements were performed by using a Vickers hardness testing machine. A total of 20 cylindershaped test specimens with a diameter of 13 mm and thickness of 1 mm were prepared to evaluate colour change (?E). Analysis of variance was used to determine significant differences among groups. Paired t and Tukey Post-Hoc tests were performed to investigate significant differences among subgroups at all time intervals (p<0.05). Results: It was found that while the percentage absorption value at T7(7 days) of the auto-polymerizing (A) groups storaged in artificial saliva + nasal secretion were the highest (0.057±0.119), the percentage absorption value at T15(15 days) of the D groups storaged in artificial nasal secretion were the lowest (0.013±0.09). Besides, it was found that the percentage solubility value at T30(30 days) of visible ligth-cusing resin (VLC) groups storaged in artificial nasal secretion were the highest (0.016±0.003), and the percentage solubility value at T1(1 day) of the D groups storaged in distilled water were the lowest (0.01±0.02). While the highest hardness value was of T0(Dry) in group heat-polymerizing (H) (36.19±1.35), the lowest hardness value was of T0 in group D (9.83±2.48). When ?E values analysed for each group, VLC group showed the highest values (23.78±5.05) (p<0.05), group D showed the lowest values (9.06±2.82) in time (between the T0 and T30). Conclusion: The new polyamide resin was observed to show better physical properties when compared with other materials

Identification of di-substituted ureas that prevent growth of trypanosomes through inhibition of translation initiation

Some 1,3-diarylureas and 1-((1,4-trans)-4-aryloxycyclohexyl)-3-arylureas (cHAUs) activate heme-regulated kinase causing protein synthesis inhibition via phosphorylation of the eukaryotic translation initiation factor 2 (eIF2) in mammalian cancer cells. To evaluate if these agents have potential to inhibit trypanosome multiplication by also affecting the phosphorylation of eIF2 alpha subunit (eIF2 alpha), we tested 25 analogs of 1,3-diarylureas and cHAUs against Trypanosoma cruzi, the agent of Chagas disease. One of them (I-17) presented selectivity close to 10-fold against the insect replicative forms and also inhibited the multiplication of T. cruzi inside mammalian cells with an EC50 of 1-3 mu M and a selectivity of 17-fold. I-17 also prevented replication of African trypanosomes (Trypanosoma brucei bloodstream and procyclic forms) at similar doses. It caused changes in the T. cruzi morphology, arrested parasite cell cycle in G1 phase, and promoted phosphorylation of eIF2 alpha with a robust decrease in ribosome association with mRNA. The activity against T. brucei also implicates eIF2 alpha phosphorylation, as replacement of WT-eIF2 alpha with a non-phosphorylatable eIF2 alpha, or knocking down eIF2 protein kinase-3 by RNAi increased resistance to I-17. Therefore, we demonstrate that eIF2 alpha phosphorylation can be engaged to develop trypanosome-static agents in general, and particularly by interfering with activity of eIF2 kinases.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)CNPqFundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)NIHUniv Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, BR-04039032 Sao Paulo, SP, BrazilUniv Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Parasitol Mol, Rio De Janeiro, RJ, BrazilInst Butantan, Sao Paulo, SP, BrazilUniv Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, Sao Paulo, SP, BrazilBrigham & Womens Hosp, Dept Med, Hematol Lab Translat Res, 75 Francis St, Boston, MA 02115 USAHarvard Med Sch, 75 Francis St, Boston, MA 02115 USAUniv Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, BR-04039032 Sao Paulo, SP, BrazilFAPESP: 2015/20031-0FAPESP: 2014/01577-2CNPq: 445655/2014-3NIH: R01 CA152312Web of Scienc

High genetic diversity and differentiation of the babesia ovis population in Turkey

Babesia ovis is a tick‐transmitted protozoan haemoparasite causing ovine babesiosis in sheep and goats leading to considerable economic loss in Turkey and neighbouring countries. There are no vaccines available, therapeutic drugs leave toxic residues in meat and milk, and tick vector control entails environmental risks. A panel of eight mini‐ and micro‐satellite marker loci was developed and applied to study genetic diversity and substructuring of B. ovis from western, central and eastern Turkey. A high genetic diversity (He = 0.799) was found for the sample of overall B. ovis population (n = 107) analyzed. Principle component analysis (PCoA) revealed the existence of three parasite subpopulations: (a) a small subpopulation of isolates from Aydin, western Turkey; (b) a second cluster predominantly generated by isolates from western Turkey; and (c) a third cluster predominantly formed by isolates from central and eastern Turkey. Two B. ovis isolates from Israel included in the analysis clustered with isolates from central and eastern Turkey. This finding strongly suggests substructuring of a major Turkish population into western versus central–eastern subpopulations, while the additional smaller B. ovis population found in Aydin could have been introduced, more recently, to Turkey. STRUCTURE analysis suggests a limited exchange of parasite strains between the western and the central–eastern regions and vice versa, possibly due to limited trading of sheep. Importantly, evidence for recombinant genotypes was obtained in regionally interchanged parasite isolates. Important climatic differences between the western and the central/eastern region, with average yearly temperatures of 21°C versus 15°C, correspond with the identified geographical substructuring. We hypothesize that the different climatic conditions may result in variation in the activity of subpopulations of Rhipicephalus spp. tick vectors, which, in turn, could selectively maintain and transmit different parasite populations. These findings may have important implications for vaccine development and the spread of drug resistance.Instituto de PatobiologíaFil: Mira, Anabela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Unlu, Ahmet Hakan. Van Yuzuncu Yil University. Vocational School of Gevas; TurquíaFil: Bilgic, Huseyin Bilgin. Aydin Adnan Menderes University. Faculty of Veterinary Medicine. Department of Parasitology; TurquíaFil: Bakirci, Serkan. Aydin Adnan Menderes University. Faculty of Veterinary Medicine. Department of Parasitology; TurquíaFil: Hacilarlioglu, Selin. Aydin Adnan Menderes University. Faculty of Veterinary Medicine. Department of Parasitology; TurquíaFil: Karagenc, Tulin. Aydin Adnan Menderes University. Faculty of Veterinary Medicine. Department of Parasitology; TurquíaFil: Carletti, Tamara. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; ArgentinaFil: Weir, William. Universityof Glasgow. College of Medical, Veterinary and Life Sciences; Reino UnidoFil: Shiels, Brian. Universityof Glasgow. College of Medical, Veterinary and Life Sciences; Reino UnidoFil: Shkap, Varda. Kimron Veterinary Institute. Division of Parasitology; IsraelFil: Aktas, Munir. Firat University. Faculty of Veterinary Medicine. Department of Parasitology; TurquíaFil: Florin-Christensen, Monica. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schnittger, Leonhard. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

IL-24 Promotes Apoptosis through cAMP-Dependent PKA Pathways in Human Breast Cancer Cells

Interleukin 24 (IL-24) is a tumor-suppressing protein, which inhibits angiogenesis and induces cancer cell-specific apoptosis. We have shown that IL-24 regulates apoptosis through phosphorylated eukaryotic initiation factor 2 alpha (eIF2α) during endoplasmic reticulum (ER) stress in cancer. Although multiple stresses converge on eIF2α phosphorylation, the cellular outcome is not always the same. In particular, ER stress-induced apoptosis is primarily regulated through the extent of eIF2α phosphorylation and activating transcription factor 4 (ATF4) action. Our studies show for the first time that cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) activation is required for IL-24-induced cell death in a variety of breast cancer cell lines and this event increases ATF4 activity. We demonstrate an undocumented role for PKA in regulating IL-24-induced cell death, whereby PKA stimulates phosphorylation of p38 mitogen-activated protein kinase and upregulates extrinsic apoptotic factors of the Fas/FasL signaling pathway and death receptor 4 expression. We also demonstrate that phosphorylation and nuclear import of tumor suppressor TP53 occurs downstream of IL-24-mediated PKA activation. These discoveries provide the first mechanistic insights into the function of PKA as a key regulator of the extrinsic pathway, ER stress, and TP53 activation triggered by IL-24

Evaluation and Management of Antrochoanal Polyps

Antrochoanal polyps (ACPs) are benign polypoid lesions arising from the maxillary antrum and they extend into the choana. They occur more commonly in children and young adults, and they are almost always unilateral. The etiopathogenesis of ACPs is not clear. Nasal obstruction and nasal drainage are the most common presenting symptoms. The differential diagnosis should include the causes of unilateral nasal obstruction. Nasal endoscopy and computed tomography scans are the main diagnostic techniques, and the treatment of ACPs is always surgical. Functional endoscopic sinus surgery (FESS) and powered instrumentation during FESS for complete removal of ACPs are extremely safe and effective procedures. Physicians should focus on detecting the exact origin and extent of the polyp to prevent recurrence

Determination of Enzyme Inhibition and Antioxidant Activity in Some Chestnut Honeys

Sahin, Huseyin/0000-0002-6018-1494;WOS: 000435448500024Honey has always been seen as the main source of healthy natural food and folk medicines. It has been prized due to bioactive components that are responsible for different therapeutic effects. Phenolic compounds are one the parts of these components. It is claimed that these have been antioxidant agents. But it also has to be evaluated by different perspectives in biomechanics except antioxidative effects. A variety of diseases may be treated by the inhibition of some individual enzymes. A pharmaceutical drug and synthetic agents are used to treat and avert illness even though there is a potential risk named drug resistance. Nowadays, the most effective treatment seems to be the combined administration of natural foods. The study aims at investigating hyaluronidase (HYA), xanthine oxidase (XOD) and the urease enzyme inhibition of some chestnut honeys from different locations of Giresun and Ordu in Turkey. Moreover, the antioxidant activities of the prepared chestnut honey extracts were investigated by using different methods. The total phenolic (TP), total flavonoid (TF), FRAP, CUPRAC assays and DPPH, and ABTS inhibition potential were carried out using in vitro models. The enzyme IC50 values in the samples ranged from 0.793 to 12.639 mg/ml for HYA; from 0.029 to 0.106 g/ml for XO; from 0.002 to 0.054 g/ml for urease, respectively. In conclusion, honey extracts exhibited good potentials towards the inhibition of activities of the studied enzymes, and the samples also suggest a practical value for surveying natural inhibitors for specific clinical purposes. Moreover, all results can provide a basis of future studies on the alternative medicinal application related to honey.Giresun University Research Fund; Bilimsel Arastirma Projeleri (BAP) Yurutucu Sekreterligi [FEN-BAP-A-200515-70]; TUBITAK projectTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114Z370]The authors would like to thank Giresun University Research Fund, Bilimsel Arastirma Projeleri (BAP) Yurutucu Sekreterligi (Project FEN-BAP-A-200515-70) and TUBITAK project (114Z370) for the financial support. The authors are also grateful to all the beekeepers (especially Yusuf Kulekci and Mehmet Kulekci) and those who assisted with the collection of honey specimens

PREDICTIVE MODEL FOR THE ADDED VALUE OF SULTANA SEEDLESS GRAPE PRODUCTION

Turkey after USA is the second important raisin grape producer by cv “Sultana”in the world (Kara,2014). The Manisa district alone accounts for 31% of totalgrape production and 80% of the whole sultana seedless raisin grape production inTurkey. 95% of total grape output generated in Manisa is made up of Sultanaseedless grape(TUIK, 2012). In thisstudy, the added value of grape production inManisa has been calculated and according to the findings, the per capita addedvalue of grape production has been computed. In order to calculate the addedvalue of grape production in Manisa, costs of labor, fuel, fertilizer, disinfection,hormone, repair and maintenance of the businesses around have been investigated.After calculated costs had been deducted from total business income, the totaladded value of grape production in Manisa and the per capita added valueofgrape production in Manisa were attained The efficiency per hectare in the sampleproduction units, which was investigated during the field research, measures up to26.470 kg. The percentile distributions of cost items at this efficiency level are;27,8% fuel costs, 23,2% fertilizing costs, 19,9% irrigation costs, 11,4%disinfection costs, 7,5% hormone usage costs, 4,6% harvesting and transportingcosts and the rest consists of maintenance costs. When the costs are deducted from income per hectare (11.646 USD), the added value per hectare turns out to be8843 US