Chronic cannulation in the small intestine of feral pigeons (Columba livia) to assess bioavailability

We improved a method of chronic duodenal cannulation to study intestinal transport of solutes in an in vivo model (pigeon, Columba livia). A hypoallergenic cannula was inserted into the proximal part of the small intestine of pigeons and used for solution administration. Recovery from surgery was extremely rapid and animals started eating and drinking within a day. After surgery, the body mass of cannulated pigeons was stable, and no adverse effects in the weight could be detected. The method is simple, economical and useful to determine intestinal bioavailability of solutes, for nutritional and ecological studies, in intact animals without influence of anesthesia.Fil: Chediack, Juan Gabriel. Universidad Nacional de San Luis. Facultad de Ciencias Humanas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Bioquímica y Ciencias Biológicas; ArgentinaFil: Cid, Fabricio Damian. Universidad Nacional de San Luis. Facultad de Ciencias Humanas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Bioquímica y Ciencias Biológicas; ArgentinaFil: Fasulo, S. V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Ciencias Humanas; ArgentinaFil: Caviedes Vidal, Enrique Juan Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Ciencias Humanas; Argentina. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Bioquímica y Ciencias Biológicas; Argentin

Comparative study of haematology of two teleost fish (Mugil cephalus and Carassius auratus) from different environments and feeding habits

Haematological parameters are valuable indicators of fish health status. This study is aimed to provide baseline data of the blood profile of two teleost fish species living in different environments and with divergent feeding behaviour, namely the flathead grey mullet Mugil cephalus Linnaeus, 1758, a marine herbivorous fish, and the goldfish Carassius auratus (Linnaeus, 1758), a freshwater omnivorous fish. Using an automated system coupled with flow cytometry and light microscopy, significant variations were found between M. cephalus and C. auratus blood parameters, except for haemoglobin concentration (Hgb). A significant increase in red blood cell count (RBC) and haematocrit (Hct) levels, associated with reduced mean corpuscular volume (MCV), was revealed in mullets in respect to goldfish. These data may be attributable to differences in fish species, or to their divergent physiological activeness as high RBC values are associated with fast movement and high activity with streamlined bodies, or to environmental factors such as water salinity, an increase in which may lead to erythropoiesis as an adaptive process in seawater fish. Additionally, lower values of white blood cell count (WBC) and thrombocyte count (TC) were recorded in mullets with respect to goldfish, and these changes may be due to divergent feeding habits of the two fish species, or to their different environments since increased salinity may inversely affect WBC. Overall, findings from this study provide a better understanding of the influences of divergent environmental conditions and feeding habits on fish blood parameters. The combined use of an automatic haematological count with flow cytometry was demonstrated to be effective for an early assessment of blood parameters in different fish species

The Endoscopic Management of Zenker’s Diverticulum: A Comprehensive Review

Zenker’s Diverticulum (ZD) is the most common hypopharyngeal diverticulum; however, it is often underdiagnosed. It results from the herniation of the mucosa and submucosa through Killian’s Triangle. Dysphagia is the primary symptom, occurring in 80–90% of cases. The primary goal of treatment is to transect the cricopharyngeal muscle (CM) and connect the ZD cavity to the esophageal lumen. Traditional treatments include surgical open transcervical diverticulectomy and CM septomyotomy, using rigid or flexible endoscopes. However, surgery is burdened by technical difficulties and not negligible rates of adverse events (AEs). For this reason, endoscopic techniques for ZD treatment have gained traction in recent years. Flexible endoscopic septum division (FESD), introduced nearly 20 years ago, involves a full-thickness incision of the diverticular septum. The advent of third-space endoscopy has led to the application of these techniques to ZD treatment as well. Zenker-POEM (Z-POEM) and, subsequently, Per Oral Endoscopic Septomyotomy (POES) have been developed. Hybrid techniques, such as Peroral Endoscopic Diverticulotomy (POED) and tunneling-free methods, represent additional ZD treatment options. This review outlines the armamentarium of ZD endoscopic management, summarizing the characteristics of these techniques, their benefits and limitations, and highlighting future research directions

VAC-Stent in the Treatment of Post-Esophagectomy Anastomotic Leaks: A New “Kid on the Block” Who Marries the Best of Old Techniques—A Review

Esophagectomy, while a pivotal treatment for esophageal cancer, is not without adverse events. Among these, anastomotic leak (AL) is the most feared complication, threatening patient lives and incurring significant healthcare costs. The management of AL is complex and lacks standardization. Given the high morbidity and mortality rates associated with redo-surgery, which poses risks for already fragile patients, various endoscopic treatments have been developed over time. Self-expandable metallic stents (SEMSs) were the most widely used treatment until the early 2000s. The mechanism of action of SEMSs includes covering the wall defect, protecting it from secretions, and promoting healing. In 2010, endoscopic vacuum therapy (EVT) emerged as a viable alternative for treating ALs, quickly gaining acceptance in clinical practice. EVT involves placing a dedicated sponge under negative pressure inside or adjacent to the wall defect, aiming to clear the leak and promote granulation tissue formation. More recently, the VAC-Stent entered the scenario of endoscopic treatment of post-esophagectomy ALs. This device combines a fully covered SEMS with an integrated EVT sponge, blending the ability of SEMSs to exclude defects and maintain the patency of the esophageal lumen with the capacity of EVT to aspirate secretions and promote the formation of granulation tissue. Although the literature on this new device is not extensive, early results from the application of VAC-Stent have shown promising outcomes. This review aims to synthesize the preliminary efficacy and safety data on the device, thoroughly analyze its advantages over traditional techniques and disadvantages, explore areas for improvement, and propose future directions

Hypercoagulability in splenectomized thalassemic patients detected by whole-blood thromboelastometry, but not by thrombin generation in platelet-poor plasma

Background: The mechanisms responsible for the increased thrombotic risk associated with thalassemia are still unclear. They might be related to the effects of red blood cell or endothelial cell derangements, increased numbers of platelets as well as abnormal plasma coagulation. Design and Methods: To evaluate the relative role played by cells and plasma we investigated 169 patients with thalassemia by means of thromboelastometry and thrombin generation tests. Thromboelastometry measures indices of the viscoelastic properties of whole blood after activation of coagulation and is characterized by the clotting time, which may be considered as a conventional coagulation time, clot formation time, defined as the time needed for the clot to reach a fixed firmness, and the maximum clot firmness, defined as the maximal amplitude of the tracing. Results: All the thromboelastometry parameters determined in whole blood (including shortened clotting time and clot formation time, and increased maximum clot firmness), were consistent with hypercoagulability, especially in splenectomized patients. Conversely, thrombin generation as determined in platelet-poor plasma was not. Conclusions: These findings point to blood cells and/or platelets rather than to plasma abnormalities as the most important determinants of the thrombotic risk observed in thalassemic patients who had been splenectomized. These results might have important diagnostic and therapeutic implications

Endoscopic Submucosal Dissection (ESD) for the Management of Fibrotic Non-Lifting Colorectal Lesions (NLCLs): Results from a Large Multicenter Retrospective Study

: Background/Objectives: The management of non-lifting colorectal lesions (NLCLs), often resulting from previous unsuccessful treatments or biopsies, remains challenging due to submucosal fibrosis that prevents adequate lifting. Endoscopic submucosal dissection (ESD) is a viable option for achieving complete resection in such cases. However, when standard ESD is not feasible, conversion to hybrid ESD (H-ESD) has been proposed as a rescue strategy. This study aimed to assess ESD's feasibility, effectiveness, and safety for NLCLs, including cases requiring conversion to H-ESD, when performed by experienced endoscopists in tertiary referral centers. Methods: In this multicenter retrospective study, data from patients with NLCLs treated by ESD/H-ESD between January 2009 and September 2022 were analyzed. The primary endpoint was the recurrence rate (RR). Secondary endpoints included the adverse event (AE) rate, technical success (TS) rate (en bloc resection regardless of technique), complete resection (CR), curative resection (cR) rates, and surgical intervention rate. Predictors of ESD technical success were identified. Results: In total, 178 patients with NLCLs were included (52 previously biopsied, 126 recurrent after previous resection). ESD was used in 111 (62.4%) and H-ESD in 67 (37.6%) cases. During a median follow-up of 373 days (IQR 540), the overall RR was 3.6%. The overall AE rate was 13.4%, and perforation was the most frequent (8.4%). All AEs were successfully managed endoscopically. The TS rate was 71.9%, significantly higher in previously biopsied lesions compared to recurrent ones (78.8% vs. 55.6%, p = 0.04). On multivariate analysis, rectal location (p < 0.001), F1 fibrosis (p = 0.026), and previously biopsied lesions (p = 0.006) predicted ESD TS without the need for conversion to H-ESD. Conclusions: ESD/H-ESD is feasible and safe for NLCLs when performed by experienced operators, with low RR amenable to endoscopic treatment. Previously biopsied lesions, rectal location, and low fibrosis predict ESD TS

The Endoscopic Management of Anastomotic Strictures After Esophagogastric Surgery: A Comprehensive Review of Emerging Approaches Beyond Endoscopic Dilation

Anastomotic strictures are a common complication following esophagogastric surgery, with prevalence varying depending on the type of surgery and anatomical site. These strictures can lead to debilitating symptoms such as dysphagia, pain, and malabsorption, significantly impacting patients’ quality of life. Endoscopic treatment of anastomotic strictures has established a role as the first-line strategy in this setting instead of revision surgery, offering benefits in terms of lower morbidity. Various endoscopic methods are available for anastomotic stricture management, including balloon dilation, stent placement, the new lumen-apposing metal stent, and endoscopic incision techniques. However, there is currently no strong evidence and established guidelines for the optimal treatment strategy. Available data suggest that endoscopic treatments, when performed in tertiary referral centers, can provide favorable outcomes in terms of symptom relief and reduced need for rescue surgical intervention. Nonetheless, challenges remain regarding the management of recurrent strictures and procedural complications, underscoring the need for a personalized, multidisciplinary approach to optimize clinical outcomes. This review aims to provide an updated overview of endoscopic techniques and available evidence with a focus on the most recent technologies, supporting clinicians in effectively managing anastomotic strictures in complex clinical settings

The Role of Therapeutic Endoscopic Ultrasound in Management of Malignant Double Obstruction (Biliary and Gastric Outlet): A Comprehensive Review with Clinical Scenarios

Endoscopic ultrasound (EUS)-guided interventions have revolutionized the management of malignant biliary obstruction (MBO) and gastric outlet obstruction (GOO), providing minimally invasive alternatives with improved outcomes. These procedures have significantly reduced the need for high-risk surgical interventions or percutaneous alternatives and have provided effective palliative care for patients with advanced gastrointestinal and bilio-pancreatic malignancies. EUS-guided biliary drainage (EUS-BD) techniques, including hepaticogastrostomy (EUS-HGS), choledochoduodenostomy (EUS-CDS), and antegrade stenting (EUS-AS), offer high technical and clinical success rates, with a good safety profile particularly when Endoscopic Retrograde Cholangiopancreatography (ERCP) is not feasible. EUS-HGS, which allows biliary drainage by trans-gastric route, is primarily used for proximal stenosis or in case of surgically altered anatomy; EUS-CDS with Lumen-Apposing Metal Stent (LAMS) for distal MBO (dMBO), EUS-AS as an alternative of EUS-HGS in the bridge-to-surgery scenario or when retrograde access is not possible and EUS-guided gallbladder drainage (EUS-GBD) with LAMS in case of dMBO with cystic duct patent without dilation of common bile duct (CDB). EUS-guided gastroenterostomy (EUS-GE) has already established its role as an effective alternative to surgical GE and enteral self-expandable metal stent, providing relief from GOO with fewer complications and faster recovery times. However, we do not yet have strong evidence on how to combine the different EUS-guided drainage techniques with EUS-GE in the setting of double obstruction. This comprehensive review aims to synthesize growing evidence on this topic by randomized controlled trials, cohort studies, and case series not only to summarize the efficacy, safety, and technical aspects of these procedures but also to propose a treatment algorithm based essentially on the anatomy and stage of the neoplasm to guide clinical decision-making, incorporating the principles of personalized medicine. This review also highlights the transformative impact of EUS-guided interventions on the treatment landscape for MBO and GOO. These techniques offer safer and more effective options than traditional approaches, with the potential for widespread clinical adoption. Further research is needed to refine these procedures, expand their applications, and improve patient care and quality of life

Paracellular Absorption: A Bat Breaks the Mammal Paradigm

Bats tend to have less intestinal tissue than comparably sized nonflying mammals. The corresponding reduction in intestinal volume and hence mass of digesta carried is advantageous because the costs of flight increase with load carried and because take-off and maneuverability are diminished at heavier masses. Water soluble compounds, such as glucose and amino acids, are absorbed in the small intestine mainly via two pathways, the transporter-mediated transcellular and the passive, paracellular pathways. Using the microchiropteran bat Artibeus literatus (mean mass 80.6±3.7 g), we tested the predictions that absorption of water-soluble compounds that are not actively transported would be extensive as a compensatory mechanism for relatively less intestinal tissue, and would decline with increasing molecular mass in accord with sieve-like paracellular absorption. Using a standard pharmacokinetic technique, we fed, or injected intraperitonealy the metabolically inert carbohydrates L-rhamnose (molecular mass = 164 Da) and cellobiose (molecular mass = 342 Da) which are absorbed only by paracellular transport, and 3-O-methyl-D-glucose (3OMD-glucose) which is absorbed via both mediated (active) and paracellular transport. As predicted, the bioavailability of paracellular probes declined with increasing molecular mass (rhamnose, 90±11%; cellobiose, 10±3%, n = 8) and was significantly higher in bats than has been reported for laboratory rats and other mammals. In addition, absorption of 3OMD-glucose was high (96±11%). We estimated that the bats rely on passive, paracellular absorption for more than 70% of their total glucose absorption, much more than in non-flying mammals. Although possibly compensating for less intestinal tissue, a high intestinal permeability that permits passive absorption might be less selective than a carrier-mediated system for nutrient absorption and might permit toxins to be absorbed from plant and animal material in the intestinal lumen

Dietary and Behavioral Interventions Protect against Age Related Activation of Caspase Cascades in the Canine Brain

Lifestyle interventions such as diet, exercise, and cognitive training represent a quietly emerging revolution in the modern approach to counteracting age-related declines in brain health. Previous studies in our laboratory have shown that long-term dietary supplementation with antioxidants and mitochondrial cofactors (AOX) or behavioral enrichment with social, cognitive, and exercise components (ENR), can effectively improve cognitive performance and reduce brain pathology of aged canines, including oxidative damage and Aβ accumulation. In this study, we build on and extend our previous findings by investigating if the interventions reduce caspase activation and ceramide accumulation in the aged frontal cortex, since caspase activation and ceramide accumulation are common convergence points for oxidative damage and Aβ, among other factors associated with the aged and AD brain. Aged beagles were placed into one of four treatment groups: CON – control environment/control diet, AOX– control environment/antioxidant diet, ENR – enriched environment/control diet, AOX/ENR– enriched environment/antioxidant diet for 2.8 years. Following behavioral testing, brains were removed and frontal cortices were analyzed to monitor levels of active caspase 3, active caspase 9 and their respective cleavage products such as tau and semaphorin7a, and ceramides. Our results show that levels of activated caspase-3 were reduced by ENR and AOX interventions with the largest reduction occurring with combined AOX/ENR group. Further, reductions in caspase-3 correlated with reduced errors in a reversal learning task, which depends on frontal cortex function. In addition, animals treated with an AOX arm showed reduced numbers of cells expressing active caspase 9 or its cleavage product semaphorin 7A, while ENR (but not AOX) reduced ceramide levels. Overall, these data demonstrate that lifestyle interventions curtail activation of pro-degenerative pathways to improve cellular health and are the first to show that lifestyle interventions can regulate caspase pathways in a higher animal model of aging