scholarly journals Modulation of Intestinal Phosphate Transport in Young Goats Fed a Low Phosphorus Diet

2021 ◽  
Vol 22 (2) ◽  
pp. 866
Author(s):  
Joie L. Behrens ◽  
Nadine Schnepel ◽  
Kathrin Hansen ◽  
Karin Hustedt ◽  
Marion Burmester ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Phosphate Transport ◽  
Ussing Chambers ◽  
Intestinal Epithelia ◽  
Pi Transport ◽  
Low Phosphorus ◽  
Small Intestinal ◽  
Underlying Mechanisms ◽  
Growing Goats ◽  
1,25 Dihydroxy Vitamin D3

The intestinal absorption of phosphate (Pi) takes place transcellularly through the active NaPi-cotransporters type IIb (NaPiIIb) and III (PiT1 and PiT2) and paracellularly by diffusion through tight junction (TJ) proteins. The localisation along the intestines and the regulation of Pi absorption differ between species and are not fully understood. It is known that 1,25-dihydroxy-vitamin D3 (1,25-(OH)2D3) and phosphorus (P) depletion modulate intestinal Pi absorption in vertebrates in different ways. In addition to the apical uptake into the enterocytes, there are uncertainties regarding the basolateral excretion of Pi. Functional ex vivo experiments in Ussing chambers and molecular studies of small intestinal epithelia were carried out on P-deficient goats in order to elucidate the transepithelial Pi route in the intestine as well as the underlying mechanisms of its regulation and the proteins, which may be involved. The dietary P reduction had no effect on the duodenal and ileal Pi transport rate in growing goats. The ileal PiT1 and PiT2 mRNA expressions increased significantly, while the ileal PiT1 protein expression, the mid jejunal claudin-2 mRNA expression and the serum 1,25-(OH)2D3 levels were significantly reduced. These results advance the state of knowledge concerning the complex mechanisms of the Pi homeostasis in vertebrates.

271 Investigating the Relationship Between Nursery Pig Performance and Markers of Intestinal Morphology and Integrity

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 100-101
Author(s):  
Carson M De Mille ◽  
Nicholas K Gabler
Keyword(s):  
Active Transport ◽  
Feed Intake ◽  
Ex Vivo ◽  
Intestinal Morphology ◽  
Ussing Chambers ◽  
Nursery Pig ◽  
Pig Performance ◽  
Positive Correlations ◽  
And Function ◽  
Time Point

Abstract Weaning induces major structural and function changes to the small intestine of pigs and they transition from milk to solid feedstuffs. Thus, the objective of this study was to determine how intestinal morphology and function markers relate to feed intake and growth rates of nursery pig. Forty-eight weaned pigs (5.63 ± 0.50 kg) were randomly selected, individually penned and fed a common diet. Pig bodyweights and feed intake were determined at d 2, 7, and 21. At each time point, 16 pigs were randomly selected and euthanized. Sections of ileum were assessed for morphology [villus height (VH), crypt depth (CD) and VH:CD] and ex vivo transepithelial resistance (TER), macromolecule permeability (FD4), and active transport of glucose and glutamine via modified Ussing chambers. Within each period (d 0–2, 0–7, and 0–21), Pearson correlations were performed between ADG, ADFI, VH, VH:CD, TER, FD4 and active transport of glucose and glutamine. At d 2 post-weaning, no correlations (P > 0.05) were observed between performance and intestinal variables. By d 7, moderate positive correlations between VH and ADFI (r = 0.69, P = 0.005), VH and ADG (r = 0.68, P = 0.006) were reported. At 21 d post-weaning, moderate positive correlations were still observed for VH and ADFI (r = 0.55, P = 0.026) and between VH and ADG (r = 0.51, P = 0.042). Interestingly, ADFI and ADG tended to be negatively correlated with active glucose transport (r = -0.45, P = 0.083 and r = -0.47, P = 0.064, respectively) and active glutamine transport (r = -0.45, P = 0.083 and r = -0.46, P = 0.073, respectively). Markers of ileal integrity (TER and FD4) were not correlated with ADG or ADFI at any time point. Altogether, these data highlight the importance of intestinal morphology on early nursery pig performance.

scholarly journals Antagonism of Adherent Invasive E. coli LF82 With Human α-defensin 5 in the Follicle-associated Epithelium of Patients With Ileal Crohn’s Disease

2020 ◽  
Author(s):  
Lina Y Alkaissi ◽  
Martin E Winberg ◽  
Stéphanie DS Heil ◽  
Staffan Haapaniemi ◽  
Pär Myrelid ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Ex Vivo ◽  
Ussing Chambers ◽  
E Coli ◽  
Follicle Associated Epithelium ◽  
Vitro Model ◽  
Set Up

Abstract Background The first visible signs of Crohn’s disease (CD) are microscopic erosions over the follicle-associated epithelium (FAE). The aim of the study was to investigate the effects of human α-defensin 5 (HD5) on adherent-invasive Escherichia coli LF82 translocation and HD5 secretion after LF82 exposure in an in vitro model of human FAE and in human FAE ex vivo. Methods An in vitro FAE-model was set up by the coculture of Raji B cells and Caco-2-cl1 cells. Ileal FAE from patients with CD and controls were mounted in Ussing chambers. The effect of HD5 on LF82 translocation was studied by LF82 exposure to the cells or tissues with or without incubation with HD5. The HD5 secretion was measured in human FAE exposed to LF82 or Salmonella typhimurium. The HD5 levels were evaluated by immunofluorescence, immunoblotting, and ELISA. Results There was an increased LF82 translocation across the FAE-model compared with Caco-2-cl1 (P < 0.05). Incubation of cell/tissues with HD5 before LF82 exposure reduced bacterial passage in both models. Human FAE showed increased LF82 translocation in CD compared with controls and attenuated passage after incubation with sublethal HD5 in both CD and controls (P < 0.05). LF82 exposure resulted in a lower HD5 secretion in CD FAE compared with controls (P < 0.05), whereas Salmonella exposure caused equal secretion on CD and controls. There were significantly lower HD5 levels in CD tissues compared with controls. Conclusions Sublethal HD5 reduces the ability of LF82 to translocate through FAE. The HD5 is secreted less in CD in response to LF82, despite a normal response to Salmonella. This further implicates the integrated role of antimicrobial factors and barrier function in CD pathogenesis.

268 In-feed Antibiotics Elicit Intestinal Integrity Modifications Early in Post-weaning Life

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 99-99
Author(s):  
Jessica M Johnson ◽  
Emma T Helm ◽  
Nicholas K Gabler ◽  
Eric R Burrough ◽  
Carson M De Mille
Keyword(s):  
Growth Performance ◽  
Fixed Effects ◽  
Ex Vivo ◽  
Phase 1 ◽  
Physiological Mechanisms ◽  
Nursery Pigs ◽  
Ussing Chambers ◽  
Intestinal Integrity ◽  
And Function ◽  
Dietary Treatments

Abstract The physiological mechanisms by which in-feed antibiotics improve pig growth performance are largely unknown. One proposed mode of action is improvements in intestinal integrity and function. Therefore, the objective of this study was to test the hypothesis that in-feed therapeutic and sub-therapeutic antibiotics would improve intestinal integrity and function in nursery pigs. Twenty-four weaned pigs (6.1±1.1 kg BW) were randomly allotted to individual pens and assigned one of three dietary treatments as follows (n = 8 pigs/trt): 1) control, no antibiotics (CON), 2) CON + sub-therapeutic chlortetracycline [40 ppm in feed (sCTC)], and 3) CON + chlortetracycline-tiamulin [400 ppm + 35 ppm, respectively (CTCDen)]. The study consisted of two consecutive 14 d phases. Chlortetracycline-tiamulin was only fed in phase 1, sCTC was fed in both phases. Phase 1 and 2 ADG, ADFI, and G:F were determined. After 28 d, ileal and colonic ex vivo intestinal integrity was assessed via transepithelial resistance (TER) and macromolecule flux (FD4) in modified Ussing chambers. All data were analyzed for the fixed effects of treatment and start BW as a covariate. In phase 1, compared with CON and sCTC, CTCDen tended to have greater ADG (0.28, 0.31, and 0.33 kg/d, respectively, P = 0.10) and ADFI (0.28, 0.30, and 0.35 kg/d, respectively, P = 0.09). No differences in phase 1 G:F were observed (P = 0.11). Phase 2 ADG, ADFI, and G:F did not differ (P > 0.10). Further, ileal TER and FD4 did not differ (P > 0.10). Colonic TER tended to be increased in sCTC compared with CON and CTCDen (78, 56, and 59 Ω/cm2, respectively, P = 0.07). Compared with CON, colonic FD4 flux was decreased in sCTC and CTCDen by 35–40% (P = 0.03). Altogether, these data indicate that in-feed antibiotics improve colon integrity early in production which may contribute to improved growth performance.

scholarly journals Apoptosis in small intestinal epithelia from p53-null mice: evidence for a delayed, p53-indepdendent G2/M-associated cell death after γ-irradiation

Oncogene ◽  
1997 ◽  
Vol 14 (23) ◽  
pp. 2759-2766 ◽  
Author(s):  
Anita J Merritt ◽  
Terence D Allen ◽  
Christopher S Potten ◽  
John A Hickman
Keyword(s):  
Cell Death ◽  
Γ Irradiation ◽  
Intestinal Epithelia ◽  
Small Intestinal

scholarly journals Total flavonoids from Astragalus alleviate endothelial dysfunction by activating the Akt/eNOS pathway

2017 ◽  
Vol 46 (6) ◽  
pp. 2096-2103 ◽  
Author(s):  
Qian Liu ◽  
Ling Zhang ◽  
Qiyuan Shan ◽  
Yuxia Ding ◽  
Zhaocai Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Vascular Endothelial Cells ◽  
Ex Vivo ◽  
Umbilical Vein ◽  
Cell Counting ◽  
Total Flavonoids ◽  
Vascular Endothelial ◽  
Protective Effects ◽  
Hypoxic Conditions ◽  
Underlying Mechanisms

Objective To investigate the vasodilative and endothelial-protective effects and the underlying mechanisms of total flavonoids from Astragalus (TFA). Methods The vasodilative activities of TFA were measured with a myograph ex vivo using rat superior mesenteric arterial rings. The primary human umbilical vein endothelial cell (HUVEC) viabilities were assayed using the cell counting kit-8 after hypoxia or normoxia treatment with or without TFA. Akt, P-Akt, eNOS, P-eNOS, Erk, P-Erk, Bcl-2 and Bax expression were analyzed using western blotting. Results TFA showed concentration-dependent vasodilative effects on rat superior mesenteric arterial rings, but had no effects on normal or potassium chloride precontracted arterial rings. TFA did not affect HUVEC viabilities in normoxia, but dramatically promoted cell proliferation in the concentration range of 1 to 30 µg/mL under hypoxia. Moreover, TFA significantly increased the ratios of P-Akt/Akt and P-eNOS/eNOS in vascular endothelial cells under hypoxic conditions, but did not change the P-Erk/Erk or Bcl-2/Bax ratios. Conclusions TFA might exhibit vasorelaxant and endothelial-protective effects via the Akt/eNOS signaling pathway.

scholarly journals Lymphatic Vascular Structures: A New Aspect in Proliferative Diabetic Retinopathy

2018 ◽  
Vol 19 (12) ◽  
pp. 4034 ◽  
Author(s):  
Erika Gucciardo ◽  
Sirpa Loukovaara ◽  
Petri Salven ◽  
Kaisa Lehti
Keyword(s):  
Diabetic Retinopathy ◽  
Ex Vivo ◽  
Tissue Level ◽  
Clinical Samples ◽  
Related Factors ◽  
Disease Etiology ◽  
Working Age ◽  
Vascular Structures ◽  
Underlying Mechanisms ◽  
End Stage

Diabetic retinopathy (DR) is the most common diabetic microvascular complication and major cause of blindness in working-age adults. According to the level of microvascular degeneration and ischemic damage, DR is classified into non-proliferative DR (NPDR), and end-stage, proliferative DR (PDR). Despite advances in the disease etiology and pathogenesis, molecular understanding of end-stage PDR, characterized by ischemia- and inflammation-associated neovascularization and fibrosis, remains incomplete due to the limited availability of ideal clinical samples and experimental research models. Since a great portion of patients do not benefit from current treatments, improved therapies are essential. DR is known to be a complex and multifactorial disease featuring the interplay of microvascular, neurodegenerative, metabolic, genetic/epigenetic, immunological, and inflammation-related factors. Particularly, deeper knowledge on the mechanisms and pathophysiology of most advanced PDR is critical. Lymphatic-like vessel formation coupled with abnormal endothelial differentiation and progenitor cell involvement in the neovascularization associated with PDR are novel recent findings which hold potential for improved DR treatment. Understanding the underlying mechanisms of PDR pathogenesis is therefore crucial. To this goal, multidisciplinary approaches and new ex vivo models have been developed for a more comprehensive molecular, cellular and tissue-level understanding of the disease. This is the first step to gain the needed information on how PDR can be better evaluated, stratified, and treated.

Stanniocalcin: a novel protein regulating calcium and phosphate transport across mammalian intestine

1998 ◽  
Vol 274 (1) ◽  
pp. G96-G102 ◽  
Author(s):  
Karen L. Madsen ◽  
Michele M. Tavernini ◽  
Christine Yachimec ◽  
Donna L. Mendrick ◽  
Pedro J. Alfonso ◽  
...  
Keyword(s):  
Calcium Absorption ◽  
Short Circuit ◽  
Regulatory Protein ◽  
Chinese Hamster ◽  
Phosphate Transport ◽  
Simultaneous Increase ◽  
Rat Intestine ◽  
Glycoprotein Hormone ◽  
Phosphate Absorption ◽  
Ussing Chambers

Stanniocalcin (STC) is an anti-hypercalcemic glycoprotein hormone previously identified in the corpuscles of Stannius in bony fish and recently in the human genome. This study undertook to express human STC in Chinese hamster ovary (CHO) cells and to determine its effects on calcium and phosphate absorption in swine and rat intestine. Unidirectional mucosal-to-serosal ( J m→s) and serosal-to-mucosal ( J s→m)45Ca and32P fluxes were measured in vitro in duodenal tissue in voltage-clamped Ussing chambers. Addition of STC (10–100 ng/ml) to the serosal surface of the duodenum resulted in a simultaneous increase in calcium J m→s and J s→mfluxes, with a subsequent reduction in net calcium absorption. This was coupled with an STC-stimulated increase in phosphate absorption. Intestinal conductance was increased at the highest dose of STC (100 ng/ml) in swine tissue. The addition of STC to the mucosal surface had no effect on calcium and phosphate fluxes. STC at doses of 10–1,000 ng/ml had no effect on short-circuit current in any region of the rat intestine. In conclusion, human recombinant STC decreases the absorption of calcium and stimulates the absorption of phosphate in both swine and rat duodenum. STC is a novel regulatory protein that regulates mammalian intestinal calcium and phosphate transport.

scholarly journals Ex vivo activity of cytotoxic drugs and targeted agents in small intestinal neuroendocrine tumors

2018 ◽  
Vol 25 (4) ◽  
pp. 471-480
Author(s):  
Kosmas Daskalakis ◽  
Olov Norlén ◽  
Andreas Karakatsanis ◽  
Per Hellman ◽  
Rolf Larsson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Sensitivity ◽  
Kinase Inhibitors ◽  
Ex Vivo ◽  
Great Variability ◽  
Protein Kinase Inhibitors ◽  
Cytotoxic Drugs ◽  
Targeted Agents ◽  
Small Intestinal ◽  
Tumor Types

Small intestinal neuroendocrine tumors (SI-NETs) are generally considered resistant to systemic treatment. To date, predictive markers for drug activity are lacking. Tumor samples from 27 patients with SI-NETs were analyzed ex vivo for sensitivity to a panel of cytotoxic drugs and targeted agents using a short-term total cell kill assay. Samples of renal cancer, colorectal cancer (CRC), ovarian cancer and chronic lymphocytic leukemia (CLL) were included for comparison. For the SI-NET subset, drug sensitivity was analyzed in relation to clinicopathological variables and pre-treatment biomarkers. For cytotoxic drugs, SI-NETs demonstrated similar or higher sensitivity to 5-FU, platinum, gemcitabine and doxorubicin compared with CRC. For several of the targeted kinase inhibitors, SI-NET was among the most sensitive solid tumor types. CLL and ovarian cancer were generally the most sensitive tumor types to both cytotoxic drugs and protein kinase inhibitors. SI-NET was more sensitive to the mTOR inhibitor sirolimus than the other solid tumor types tested. Individual SI-NET samples demonstrated great variability in ex vivo sensitivity for most drugs. Cross-resistance between different drugs also varied considerably, being higher among protein kinase inhibitors. Age, stage, grade, peritoneal carcinomatosis and extra-abdominal metastases as well as serum chromogranin A and urine 5-HIAA concentrations at diagnosis did not correlate to drug sensitivity ex vivo. SI-NETs exhibit intermediate sensitivity ex vivo to cytotoxic and targeted drugs. Clinicopathological factors and currently used biomarkers are not clearly associated to ex vivo sensitivity, challenging these criteria for treatment decisions in SI-NET. The great variability in drug sensitivity calls for individualized selection of therapy.

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