scholarly journals Effect of Fluoxetine and Paroxetine on Intestinal Motility in Presence of Ondansetron in ex-vivo Model

2020 ◽  
Vol 1 (3) ◽  
pp. 5
Author(s):  
Ayesha Afzal ◽  
Ammara Khan ◽  
Khalida Ajmal ◽  
Abeera Sikandar ◽  
Saima Rafiqu ◽  
...  

Objective: To understand the effects of fluoxetine and paroxetine with ondansetron on the intestinal motility of rabbit ileum. Study Design: Observational study. Place and Duration of Study: The study was conducted from March to April 2018 in a multidisciplinary lab of Army Medical College, Rawalpindi.Materials and Methods: The contractile effect of intestinal motility was recorded in the power lab. Subjects were twenty four healthy rabbits (Oryctolagus Cuniculus). Semi log dose-response curve was constructed for increasing concentrations of serotonin, ondansetron, fluoxetine, and paroxetine (10-9 to 10-6 M) alone and then in the presence of a fixed concentration of ondansetron (10-6 M) to observe the modulatory role of ondansetron. The serotonin mediated contractions were taken as control.Results: Ondansetron and serotonin caused an increase in the contractile response of rabbits ileum. A depressive response was observed when the contractions were recorded with increased concentration of fluoxetine and paroxetine in the presence of ondansetron. Conclusion: Ondansetron when used concomitantly with selective serotonin reuptake inhibitors(SSRIs), abolishes their antidepressant effects by causing a decrease in the intestinal motility of rabbit ileum.

2020 ◽  
Author(s):  
JR Ferreira ◽  
GQ Teixeira ◽  
E Neto ◽  
C Ribeiro-Machado ◽  
AM Silva ◽  
...  

Abstract The authors have withdrawn this preprint due to author disagreement.


2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
T. Secher ◽  
F. Rodrigues Coelho ◽  
N. Noulin ◽  
A. Lino dos Santos Franco ◽  
V. Quesniaux ◽  
...  

Inhaled bacterial lipopolysaccharides (LPSs) induce an acute tumour necrosis factor-alpha (TNF-α-) dependent inflammatory response in the murine airways mediated by Toll-like receptor 4 (TLR4) via the myeloid differentiation MyD88 adaptor protein pathway. However, the contractile response of the bronchial smooth muscle and the role of endogenous TNFα in this process have been elusive. We determined the in vivo respiratory pattern of C57BL/6 mice after intranasal LPS administration with or without the presence of increasing doses of methacholine (MCh). We found that LPS administration altered the basal and MCh-evoked respiratory pattern that peaked at 90 min and decreased thereafter in the next 48 h, reaching basal levels 7 days later. We investigated in controlled ex vivo condition the isometric contraction of isolated tracheal rings in response to MCh cholinergic stimulation. We observed that preincubation of the tracheal rings with LPS for 90 min enhanced the subsequent MCh-induced contractile response (hyperreactivity), which was prevented by prior neutralization of TNFα with a specific antibody. Furthermore, hyperreactivity induced by LPS depended on an intact epithelium, whereas hyperreactivity induced by TNFα was well maintained in the absence of epithelium. Finally, the enhanced contractile response to MCh induced by LPS when compared with control mice was not observed in tracheal rings from TLR4- or TNF- or TNF-receptor-deficient mice. We conclude that bacterial endotoxin-mediated hyperreactivity of isolated tracheal rings to MCh depends upon TLR4 integrity that signals the activation of epithelium, which release endogenous TNFα.


1998 ◽  
Vol 80 (11) ◽  
pp. 852-858 ◽  
Author(s):  
Helge Einar Roald ◽  
Torstein Lyberg ◽  
Inger Anne Hagberg

SummarySince the role of leukocytes found present in thrombi and haemo-static plugs is not clearly understood, we have investigated the interaction between leukocytes and growing thrombi in a human ex vivo model of arterial thrombogenesis. At a wall shear rate characteristic of moderately stenosed arteries (2600 s–1), granulocytes selectively accumulated at the luminal surface of platelet thrombi. The leukocyte adhesion seemed independent of fibrin formation and was clearly correlated to thrombus growth and platelet activation. In contrast, flow cytometry revealed that the expression of adhesion molecules (CD11a, CD11b, CD11c, CD3, CD14, CD62L, HLA-DR and binding of fibrinogen) on the surface of circulating leukocytes passing the thrombi was, on short term conditions (15 min), independent of thrombus growth. The adhered granulocytes probably play a pivotal role in limiting the size of the evolving thrombi, as suggested by our electron micrographs of the arterial thrombi showing lysed and phagocytosed platelets. Thus, granulocytes might play an active role in the acute/semiacute phase of local thromboregulation.


2022 ◽  
Vol 20 ◽  
Author(s):  
Tayebeh Noori ◽  
Antoni Sureda ◽  
Eduardo Sobarzo-Sánchez ◽  
Samira Shirooie

Abstract: Depressive disorder is one of the most common psychiatric syndromes that, if left untreated, can cause many disturbances in a person's functions. Numerous factors are involved in depression, including inflammation, brain-derived neurotrophic factor (BDNF), GABAergic system, hypothalamic–pituitary–adrenal (HPA) Axis, monoamine neurotransmitters (serotonin (5-HT), noradrenaline, and dopamine). Common treatments for depression are selective serotonin reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors, but these drugs have several side effects such as anxiety, diarrhea, constipation, weight loss, and sexual dysfunctions. These agents only reduce the symptoms and temporarily reduce the rate of cognitive impairment associated with depression. As a result, extensive research has recently been conducted on the potential use of antidepressant and sedative herbs. According to the available data, herbs used in traditional medicine can be significantly effective in reducing depression, depressive symptoms and improving patients' performance. The present study provides a summary of biomarkers and therapeutic goals of depression and shows that natural products such as saffron or genipin, have antidepressant effects. Some of the useful natural products and their mechanisms were evaluated. Data on various herbs and natural isolated compounds reported to prevent and reduce depressive symptoms is also discussed.


2013 ◽  
Vol 304 (10) ◽  
pp. H1328-H1336 ◽  
Author(s):  
Astra I. Chang ◽  
Monica Forero McGrath ◽  
Adolfo J. de Bold

The cardiac hormone atrial natriuretic factor (ANF or ANP) plays significant, well-established roles in a large number of physiological and pathophysiological processes, including water and electrolyte balance, blood pressure regulation, and cardiovascular growth. Understanding the regulation of its production and secretion by atrial cardiomyocytes is incomplete. We have previously established a significant role of Gi/o protein signaling in modulating ANF secretion as promoted by stretch of the atrial myocardium. In the present study, we investigated the role of Gq protein signaling and its relationship to Gi/o protein signaling using pharmacological manipulation of proximal effectors of Gαq in an ex vivo model of spontaneously beating rat atria. Phospholipase C (PLC) and protein kinase C (PKC) inhibitors dramatically increased basal secretion of ANF. Furthermore, although atrial wall stretch is a potent stimulus for secretion, stretch unexpectedly reduced ANF secretion to basal levels under PLC and PKC inhibitory conditions. Inhibition of the inositol triphosphate receptor did not appear to affect basal secretion but dose-dependently blocked stretch-secretion coupling. The results obtained demonstrate that the PLC and PKC signaling cascades play important albeit unexpected roles in the regulation of basal and stimulated ANF secretion and suggest interplay between the Gq and Gi/o protein signaling pathways.


2001 ◽  
Vol 90 (6) ◽  
pp. 2257-2268 ◽  
Author(s):  
Brendan J. Collins ◽  
Matthew G. Blum ◽  
Richard E. Parker ◽  
Andrew C. Chang ◽  
Kelly S. A. Blair ◽  
...  

The role of thromboxane (Tx) in hyperacute rejection of pig lung by human blood was studied in an ex vivo model, wherein lungs from juvenile piglets were perfused with fresh heparinized human blood. In this model, hyperacute lung rejection was characterized by an abrupt rise in pulmonary vascular resistance (PVR; >1 cmH2O · ml−1· min) and prolific Tx elaboration (>15 ng/ml) within 5 min and loss of function within 10 min. Although papaverine significantly blunted the rise in PVR (<0.2 cmH2O · ml−1· min), Tx production was not inhibited (>20 ng/ml), and florid tracheal edema was usually evident within 20 min. In contrast, both inhibition of Tx synthesis (Tx < 3 ng/ml) with OKY-046 and blockade of the Tx receptor with SQ-30741 (Tx > 20 ng/ml) were not only associated with significantly lower peak PVRs (<0.2 cmH2O · ml−1· min) but also with attenuated increase in lung wet-to-dry ratio and airway edema. In concert, elaboration of histamine and tumor necrosis factor was blunted, and median survival increased >10-fold to 2 h (SQ-30741) and >4 h (OKY-046). Depletion of the pig lung macrophages with dichloromethyl bisphosphonate in liposomes, but not Pall filtration of the human blood or liposomes alone, significantly inhibited Tx elaboration (<0.2 vs. >8 ng/ml for Pall filtration or liposomes) and blunted PVR elevation (<0.3 cmH2O · ml−1· min) during initial perfusion. C3a and histamine elaboration were inhibited, and median survival was significantly prolonged (>4 h). These findings implicate Tx in the inflammation associated with hyperacute lung rejection and demonstrate that pulmonary intravascular macrophages are critical to its elaboration.


2010 ◽  
Vol 9 (2) ◽  
pp. 271
Author(s):  
L.C. Leonardo ◽  
I.A. Isidori ◽  
T.N. Tartaglia ◽  
P.S. Pierotti ◽  
S.M. Salvitti ◽  
...  

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052095055
Author(s):  
Francesco Corallo ◽  
Chiara Scarfì ◽  
Francesca Antonia Arcadi ◽  
Caterina Formica ◽  
Marcella Di Cara ◽  
...  

Objective We conducted a narrative review to investigate whether antidepressant therapy, including the use of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) or the use of supportive drugs (i.e., citicoline or choline alfoscerate) as a substitute for antidepressant therapy, reduces depression in patients with cerebrovascular diseases. Methods A systematic search of the PubMed and Web of Science databases was performed, including review articles and other studies to identify additional citations. Only 4 of 1566 publications met the inclusion/exclusion criteria and were selected. Results Studies showed that post-stroke depression (PSD) could be treated with antidepressant therapy, as well as supportive drugs such as citicoline or choline alfoscerate, which may have antidepressant effects. Conclusions The findings support the efficacy of citicoline as a treatment for depression. Studies aimed to discover the characteristics of these psychostimulants in relation to PSD treatment should be performed.


Perfusion ◽  
2003 ◽  
Vol 18 (1_suppl) ◽  
pp. 13-21 ◽  
Author(s):  
Filip R Rega ◽  
Eddy J Vandezande ◽  
Nicole C Jannis ◽  
Geert M Verleden ◽  
Toni E Lerut ◽  
...  

If lungs could be retrieved for transplantation after circulatory arrest, the shortage of donors might be significantly alleviated. An important issue in using lungs from these so-called non-heart-beating donors is the development of a technique to assess their quality prior to transplantation without jeopardizing the life of the recipient. In our laboratory we tested the reliability of an ex vivo model for such an evaluation. We used pig lungs from optimal control animals, in casu heart-beating donors. This model enabled us to preserve and evaluate lungs with perfect function up to 24 hours after death. The intermediate assessment is performed in an isolated circuit where the lungs are being ventilated and reper-fused via the pulmonary artery (PA) with autologous and haemodiluted blood. Haemodynamic, aerodynamic and oxygenation parameters are measured at 37.5°C and a maximum PA pressure of 20 mmHg. These data were correlated with premortem values. During this ex vivo evaluation, leukocyte depletion plays an important role since neutrophils have been recognized as critical components in the inflammatory cascade, which is responsible for graft dysfunction soon and long after transplantation.


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