Publications by authors named "John Geibel"

Additive manufacturing (3D printing) has been deployed across multiple platforms to fabricate bioengineered tissues. We demonstrate the use of a Thermal Inkjet Pipette System (TIPS) for targeted delivery of cells onto manufactured substrates to design bio-bandages. Two cell lines - HEK 293 (kidney) and K7M2 wt (bone) - were applied using TIPS.

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The skeletal system is a key support structure within the body. Bones have unique abilities to grow and regenerate after injury. Some injuries or degeneration of the tissues cannot rebound and must be repaired by the implantation of foreign objects following injury or disease.

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3D bioprinting is transforming tissue engineering in medicine by providing novel methods that are precise and highly customizable to create biological tissues. The selection of a "cell ink", a printable formulation, is an integral part of adapting 3D bioprinting processes to allow for process optimization and customization related to the target tissue. Bioprinting hydrogels allows for tailorable material, physical, chemical, and biological properties of the cell ink and is suited for biomedical applications.

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Colonic epithelial cells are responsible for maintaining a delicate balance between luminal secretion and the absorption of fluids and ions. This review aims to discuss and update the model of colonic electrolyte secretion and absorption via the cystic fibrosis transmembrane regulator (CFTR), epithelial sodium channel (ENaC), Na-K-Cl cotransporters (NKCC1 and 2), Na-H exchangers (NHE1-4), colonic H,KATPase, and several other key components involved in multi-level transepithelial ion transport. Developments in our understanding of the activity, regulation, localization, and relationships of these ion transporters and their interactions have helped forge a more robust understanding of colonic ion movement that accounts for the colonic epithelium's role in mucosal pH modulation, the setting of osmotic gradients pivotal for fluid retention and secretion, and cell death regulation.

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With a limited supply of organ donors and available organs for transplantation, the aim of tissue engineering with three-dimensional (3D) bioprinting technology is to construct fully functional and viable tissue and organ replacements for various clinical applications. 3D bioprinting allows for the customization of complex tissue architecture with numerous combinations of materials and printing methods to build different tissue types, and eventually fully functional replacement organs. The main challenge of maintaining 3D printed tissue viability is the inclusion of complex vascular networks for nutrient transport and waste disposal.

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Historically, bile in the biliary tract has been considered sterile. Most of the series are based on patients with biliary tract diseases or the bile has been obtained with procedures susceptible to contamination. We evaluated the bile in a heterogeneous cohort of liver donors and recipient patients, with samples obtained in a sterile way, directly from the gallbladder and the common bile duct.

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3D Printing has become a mainstay of industry, with several applications in the medical field. One area that could benefit from 3D printing is intestinal failure due to injury or genetic malformations. We bioprinted cylindrical tubes from rat vascular cells that were sized to form biopatches.

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Background/aims: The colonic H, K ATPase (HKA2) is a heterodimeric membrane protein that exchanges luminal K for intracellular H and is involved in maintaining potassium homeostasis. Under homeostatic conditions, the colonic HKA2 remains inactive, since most of the potassium is absorbed by the small intestine. In diarrheal states, potassium is secreted and compensatory potassium absorption becomes necessary.

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Background And Aims: Among all transplanted abdominal organs, the small intestine is one of the most ischemia sensitive. Appropriate graft selection, procurement, and preservation are crucial for optimum graft and patient survival. We evaluated ischemic damage in human small intestine grafts under different hypothermic preservation conditions (cold static and continuous perfusion) and solutions: histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW).

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The stomach has unique embryologic and anatomic properties, making the study of the parietal cell technically challenging. Numerous individuals have devoted decades of research to unraveling the pathophysiological basis of this cell type. Here, we perform a scoping review of novel and methodology pertaining to the parietal cell.

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Aspirin has been widely recommended for acute and chronic conditions for over 2,000 years. Either single or repetitive doses are commonly used for analgesic and antipyretic reasons and to prevent heart attacks, stroke, and blood clot formation. Recent studies show that it can also be used chronically to dramatically reduce the risk of a variety of cancers.

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Diarrhea is one of the most commonly reported adverse effect of hemotherapy and targeted cancer therapies, such as tyrosine kinase inhibitors (TKI), which often significantly impact patient quality of life, morbidity, and mortality. Neratinib is an oral, irreversible pan-HER tyrosine kinase inhibitor, which is clinically active in HER2-positive breast cancer. Diarrhea is the most common side effect of this potent anticancer drug and the reasons for this adverse effect are still largely unclear.

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Background: The calcium-sensing receptor (CaSR) has been localized and characterized in numerous tissues throughout the body. In the mammalian gastrointestinal tract, the CaSR is known to act as a nutrient sensor and has recently been found to play a role in intestinal fluid and electrolyte balance. This study aims to demonstrate the functionality of the CaSR as a modulator of fluid secretion and absorption along the small intestine.

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Gastrointestinal illnesses pose a significant worldwide disease burden and are associated with an array of medicinal and surgical therapies. Standard pharmaceutical options have adverse effects, prompting the rise of nutraceutical or food-derivative therapies. Here, we present an overview of the current nutraceutical therapies in gastrointestinal disease.

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Vascular disease - including coronary artery disease, carotid artery disease, and peripheral vascular disease - is a leading cause of morbidity and mortality worldwide. The standard of care for restoring patency or bypassing occluded vessels involves using autologous grafts, typically the saphenous veins or internal mammary arteries. Yet, many patients who need life- or limb-saving procedures have poor outcomes, and a third of patients who need vascular intervention have multivessel disease and therefore lack appropriate vasculature to harvest autologous grafts from.

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The H,K-ATPase was identified as the primary proton secretory pathway in the gastric parietal cell and is the pharmacological target of agents suppressing acid secretion. Recently, we identified a second acid secretory protein expressed in the parietal cell, the vacuolar H-ATPase (V-type ATPase). The aim of the present study was to further characterize H-ATPase activation by modulations in extracellular calcium via the calcium sensing receptor (CaSR).

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Butyrate protects against ischemic injury to the small intestine by reducing inflammation and maintaining the structure of the intestinal barrier, but is expensive, short-lived, and cannot be administered easily due to its odor. Lactate, both economical and more palatable, can be converted into butyrate by the intestinal microbiome. This study aimed to assess in a rat model whether lactate perfusion can also protect against intestinal ischemia.

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Background/aims: L-arginine is an important mediator of cell division, wound healing, and immune function. It can be transformed by the nitric oxide synthase (NOS) to nitric oxide (NO), an important cell signaling molecule. Recent studies from our laboratory demonstrate specific effects of L-arginine (10mM) exposure on gastric acid secretion in rat parietal cells.

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Background/aim: Colorectal cancer is still considered a leading cause of death in the United States and worldwide. One potential way to improve survival besides detection is to look to new therapeutic agents that can be taken prophylactically to reduce the risk of tumor formation. For cancer cells to grow and invade, a higher (more alkaline) intracellular pH must occur.

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Stomach and Bone.

Adv Exp Med Biol

April 2018

The relation between gastrointestinal organs and bone metabolism has become clearer during the last decades. Of paramount importance is the tight and intertwined regulation of gastric acid secretion and bone metabolism in regard of diseases caused by dysfunction of any of these or intermediary organs or mediators. The importance of the functions of the endocrine modulators 1,25(OH) vitamin D (calcitriol), PTH, and calcitonin becomes clear when seeing misbalances and its impact on the skeleton.

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Background: Intestinal ischemia is observed in conditions such as mesenteric ischemia, or during traumatic events such as intestinal transplantation. Intestinal ischemia leads to pathophysiologic disruptions that present as increased fluid secretion into the intestinal lumen. We propose a novel method to detect real-time ischemic injury that is used in an in vitro model applicable to intestinal transplantation.

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Prolonged exposure to gastric acid is a leading cause of gastroesophageal reflux disease (GERD) and esophagitis. With the ever increasing number of patients showing insensitivity to proton-pump-inhibitor (PPI) therapy with recurrence of symptoms over time, alternative treatment options remain an important issue. Previous studies from our laboratory have shown that a zinc sulfate salt can inhibit HCl generation at the cellular level of the parietal cell.

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Intestinal transplantation remains a life-saving option for patients with severe intestinal failure. With the advent of advanced tissue engineering techniques, great strides have been made toward manufacturing replacement tissues and organs, including the intestine, which aim to avoid transplant-related complications. The current paradigm is to seed a biocompatible support material (scaffold) with a desired cell population to generate viable replacement tissue.

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Introduction: The small intestine is one of the most ischemia-sensitive organs used in transplantation. To better preserve the intestinal graft viability and decrease ischemia-reperfusion injury, a device for extracorporeal perfusion was developed. We present the results for the first series of perfused human intestine with an intestinal perfusion unit (IPU).

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Background: Small intestine ischemia can be seen in various conditions such as intestinal transplantation. To further understand the pathologic disruption in ischemia-reperfusion injury, we have developed a method to measure fluid changes in the intestinal lumen of rats.

Methods: Two 10-cm rat intestine segments were procured, connected to the terminal apertures of a perfusion device, and continuously infused with 3 mL of HEPES solution (control solution) containing 50 μM of fluorescein isothiocyanate (FITC)-inulin.

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