scholarly journals Features of the functional activity of macrophage link of immunity with gastroesophageal reflux disease depending on the type of reluctate: in vitro model

2018 ◽  
Vol 90 (2) ◽  
pp. 19-23 ◽  
Author(s):  
S V Lyamina ◽  
I V Maev ◽  
S V Kalish ◽  
D N Andreev ◽  
O V Kladovikova ◽  
...  

Aim. A generalized analysis of changes in functional activity of macrophages on the basis of phagocytic activity, cytokine profile, changes in the level of expression of surface markers characteristic of pro - or anti-inflammatory phenotype of the cells when exposed to reluctate. Materials and methods. Developed in vitro model of co-peritoneal macrophages of mice With57/BL6 (n=65) and reluctate patients with gastroesophageal reflux disease (GERD; n=65) having different pH values (three group comparison). Took into account the standard criteria phagocytic ability (absorption Staphylococcus aureus 9198, light microscopy), secretory activity (cytokine profile Th1/Th2, flow cytometry) and receptor characterization of macrophages (expression of CD25/80/163/206, flow cytometry). Results. The phagocytic activity of macrophages, calculated on the basis of the average number of bacteria ingested by one phagocyte, is not associated with the pH value of the added reluctate. It is established that the alkalinisation of reluctate leads to significant alteration in the expression of CD receptors - decrease M1 and increase M2. The index of total production of Th1/Тһ2 in groups progressively decreased with increasing pH of reluctate and amounted to 3.6 units in the group pH from 4.6 to 6.6; 2.8 units group a pH of 6.7-7.2 and 1.6 units in the group pH of 7.3 to 8.1, due to increased production of Th2 cytokines at offset reluctate pH to slightly alkaline side. The data obtained indicate the increase of expression and secretion of anti-inflammatory markers at an alkaline pH shift of reluctate. Analysis of the studied characteristics of the activity profile of macrophages in the proposed in vitro model justifies the need for considering the peculiarities of the functional activity of macrophages under the influence of reluctate different nature. The special importance of studying the cytokine profile and characteristics of the functional activity of macrophages in patients with GERD, given the nature of reluctate.

2016 ◽  
Vol 4 (2) ◽  
pp. 221-228 ◽  
Author(s):  
Ilker Turan ◽  
Gul Kitapcioglu ◽  
Ege Tavmergen Goker ◽  
Gulnaz Sahin ◽  
Serhat Bor ◽  
...  

2014 ◽  
Vol 146 (5) ◽  
pp. S-749
Author(s):  
Ilker Turan ◽  
Gul Kitapcioglu ◽  
Ege Tavmergen Goker ◽  
Gulnaz Sahin ◽  
Serhat Bor

2020 ◽  
Vol 12 ◽  
pp. 11
Author(s):  
Halima Sadia ◽  

Dexlansoprazole delayed release is a newly developed class of Proton Pump Inhibitor (PPI). The drug is effective in the treatment of erosive esophagitis, maintenance of eosinophilic esophagitis and relief of heartburn. Additionally, it is also beneficial in the treatment of heartburn with symptomatic gastroesophageal reflux disease. The drug offers the advantage of no dosage adjustment in patients with hepatic impairment. Dexlansoprazole inhibits the stomach acid secrection by specific inhibition of the hydrogen-potassium–ATPase in parietal cells of stomach.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4411-4411
Author(s):  
Brea Lipe ◽  
Amanda Wise ◽  
Tara L. Lin ◽  
Omar S. Aljitawi ◽  
Devon Koestler ◽  
...  

Abstract Introduction: Multiple Myeloma (MM) is an incurable cancer characterized by a pre-malignant clonal phase of disease called monoclonal gammopathy of undetermined significance (MGUS). Most patients with MGUS do not develop overt MM and the biology underlying this potential transformation is unclear. Investigations to prevent the development of MM from MGUS are limited by the relative infrequency of MGUS progression. Unfortunately, MGUS cells have historically proven difficult to grow in vitro because of slow rates of proliferation and difficulty in sustaining cell cultures. We present evidence of an in vitro model that generates MM-like plasma cells from patients diagnosed with only MGUS. We further present gene expression patterns of primary patient cells versus the induced MM cells to provide guidance as to important initiating events within our model. Methods: We collected a CD38+ cell fraction and a mononuclear (CD38-) fraction from 4 patients with MGUS using a Miltenyl Biotec column Separator. The CD38- fraction was grown in RPMI with 10% FBS and 1% sodium pyruvate with or without a polyglycolic acid/ poly L-lactic acid 90/10 (PLGA) copolymer scaffold to create 3D culture conditions. The mononuclear layer from healthy donors and the MM cell line, U266, were grown as controls. We then analyzed the initial CD38+ fraction, the initial CD38- fraction, and the CD38- fraction grown in media or 3D co-culture by flow cytometry for expression of kappa, lambda, CD38, CD138, CD45, CD19, and CD56. Gene expression analysis was performed using RNA-sequencing data from the CD38+, CD38-, cultured CD38-, and control cells. Expression of the top 100 ranked differentially expressed genes, which demonstrated the largest variation, were further analyzed using the nCounter® Analysis System (NanoString Technologies). Results: The CD38- fraction from MGUS patients grew into an adherent layer of elongated cells, consistent with bone marrow stromal cells. After several months, the stromal cells were noted to change shape and new, round cells were observed budding off from the stromal layer. Over time, the stromal layer disappeared and the round plasmacytoid cells remained. Characterization of these round cells revealed them to be plasma cells by IHC and flow cytometry. When comparing these in vitro generated cells to the initial CD38+ fraction removed from patients, the new cells showed the re-emergence of CD38 and CD138, increased expression of CD56 and CD19, and decreased expression of CD45. Gene expression analysis revealed 3 distinct populations of cells. The initial CD38- fraction separated with the healthy mononuclear layer. The initial CD38+ fraction clustered independently while the grown plasma cells clustered with the U266 cells. Analysis of the differential gene expression patterns revealed differences in the expression of immunoglobulin genes, as well as alterations in expression of extracellular matrix and cell adhesion markers including PAI-1, MMP2, COL1A2, and GREM1; and alterations in expression of mitochondrial genes. Conclusion: To our knowledge, this is the first in vitro simulation of disease progression from MGUS to MM. Our model induced the growth of plasma cells with an aggressive phenotype as assayed by flow cytometry. The gene expression profile further demonstrates gene expression patterns from our induced plasma cells consistent with MM versus MGUS. The alterations in extracellular matrix proteins as seen in our induced plasma cells are consistent with an epithelial to mesenchymal type transition implicated in disease progression, metastasis, and bone lesions. Additionally, the alterations in mitochondrial gene expression have been implicated in early disease progression in colon cancer and MM. These findings provide further evidence that our model simulates disease transformation and the expression data suggest possible pathways that may be important in myeloma disease progression that can be further evaluated in vivo. Disclosures No relevant conflicts of interest to declare.


2008 ◽  
Vol 45 (3) ◽  
pp. 243-248 ◽  
Author(s):  
Paula Yuri Sugishita Kanikadan ◽  
Jayme Antonio Aboin Sertié ◽  
Ricardo Martins Oliveira-Filho ◽  
Wothan Tavares de Lima

BACKGROUND: It is well known the association between gastroesophageal reflux disease and asthma. The hyperreactivity of the airways is a characteristic of an asthmatic. Many studies associate the increase of the airways reactivity with gastroesophageal reflux disease. AIM: In this study we have evaluated the effect of the intraluminal exposition to gastric juice of trachea on the reactivity to methacholine from rats submitted to a pulmonary allergic inflammation. METHODS: Group of rats were sensitized and challenged with ovalbumin. After 24 hours the animals were sacrificed, and their tracheae were removed to be cultured with gastric juice. The gastric juice was obtained from a donor rat. Subsequently the segments were placed into plastic plates with RPMI-1640 for incubation, under suitable atmosphere and time. After the period of incubation the segments were put into chambers for the analysis of the contractile response to methacholine. RESULTS: We observed reduction in the contractile response of trachea cultured with gastric juice from allergic rats. This result was confirmed by the pharmacological treatments with compound 48/80 and dissodium cromoglicate (mast cells blockade), L-NAME (nitric oxide inhibitor, NO), capsaicin (neuropeptides depletion) and indomethacin (ciclooxigenase inhibitor). CONCLUSIONS: Our results highlight to the existence of a complex interaction between pulmonary allergy and gastric juice in the airways. The involvement of the non-adrenergic non-cholinergic system, NO, prostanoids and mast cells are directly related to this interaction. We suggest that the reduced contractile response observed in vitro may represent a protector mechanism of the airways. Despite its presence in the human body it can not be observed due to the predominant effects of excitatory the non-adrenergic non-cholinergic system.


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