854 SEX STEROIDS METABOLISM IN BENIGN AND MALIGNANT PROSTATE TISSUE: AN EX-VIVO MODEL TO CHARACTERIZE THE ROLE OF ENZYMATIC PROFILE IN BIOLOGICAL BEHAVIOUR

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Abstract The authors have withdrawn this preprint due to author disagreement.


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.


2013 ◽  
Vol 3 ◽  
pp. 41 ◽  
Author(s):  
Vikram S. Dogra ◽  
Bhargava K. Chinni ◽  
Keerthi S. Valluru ◽  
Jean V. Joseph ◽  
Ahmed Ghazi ◽  
...  

Objective: The objective of this study is to validate if ex-vivo multispectral photoacoustic (PA) imaging can differentiate between malignant prostate tissue, benign prostatic hyperplasia (BPH), and normal human prostate tissue. Materials and Methods: Institutional Review Board's approval was obtained for this study. A total of 30 patients undergoing prostatectomy for biopsy-confirmed prostate cancer were included in this study with informed consent. Multispectral PA imaging was performed on surgically excised prostate tissue and chromophore images that represent optical absorption of deoxyhemoglobin (dHb), oxyhemoglobin (HbO2), lipid, and water were reconstructed. After the imaging procedure is completed, malignant prostate, BPH and normal prostate regions were marked by the genitourinary pathologist on histopathology slides and digital images of marked histopathology slides were obtained. The histopathology images were co-registered with chromophore images. Region of interest (ROI) corresponding to malignant prostate, BPH and normal prostate were defined on the chromophore images. Pixel values within each ROI were then averaged to determine mean intensities of dHb, HbO2, lipid, and water. Results: Our preliminary results show that there is statistically significant difference in mean intensity of dHb (P < 0.0001) and lipid (P = 0.0251) between malignant prostate and normal prostate tissue. There was difference in mean intensity of dHb (P < 0.0001) between malignant prostate and BPH. Sensitivity, specificity, positive predictive value, and negative predictive value of our imaging system were found to be 81.3%, 96.2%, 92.9% and 89.3% respectively. Conclusion: Our preliminary results of ex-vivo human prostate study suggest that multispectral PA imaging can differentiate between malignant prostate, BPH and normal prostate tissue.


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.


Endocrinology ◽  
2014 ◽  
Vol 155 (2) ◽  
pp. 568-575 ◽  
Author(s):  
Thi Y. L. Le ◽  
Anthony W. Ashton ◽  
Mahidi Mardini ◽  
Peter G. Stanton ◽  
John W. Funder ◽  
...  

Age-specific incidence of ischemic heart disease in men is higher than in women, although women die more frequently without previous symptoms; the molecular mechanism(s) are poorly understood. Most studies focus on protection by estrogen, with less attention on androgen receptor-mediated androgen actions. Our aim was to determine the role of androgens in the sex differences in cardiac damage during myocardial infarction. Mature age-matched male and female Sprague Dawley rats, intact or surgically gonadectomized (Gx), received testosterone (T) or 17β-estradiol (E2) via subdermal SILASTIC (Dow Corning Corp.) implants; a subset of male rats received dihydrotestosterone. After 21 days, animals were anesthetized, and hearts were excised and subjected to ex vivo regional ischemia-reperfusion (I-R). Hearts from intact males had larger infarcts than those from females following I-R; Gx produced the opposite effect, confirming a role for sex steroids. In Gx males, androgens (dihydrotestosterone, T) and E2 aggravated I-R-induced cardiac damage, whereas in Gx females, T had no effect and E2 reduced infarct area. Increased circulating T levels up-regulated androgen receptor and receptor for advanced glycation end products, which resulted in enhanced apoptosis aggravating cardiac damage in both males and females. In conclusion, our study demonstrates, for the first time, that sex steroids regulate autophagy during myocardial infarction and shows that a novel mechanism of action for androgens during I-R is down-regulation of antiapoptotic protein Bcl-xL (B cell lymphoma-extra large), a key controller for cross talk between autophagy and apoptosis, shifting the balance toward apoptosis and leading to aggravated cardiac damage.


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.


Toxicology ◽  
2015 ◽  
Vol 335 ◽  
pp. 72-78 ◽  
Author(s):  
G.R. Leisching ◽  
B. Loos ◽  
M.H. Botha ◽  
A.-M. Engelbrecht

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