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

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.

Persea Americana Seeds Cause Ileal Smooth Muscle Relaxation Via Stimulation of α-1 Adrenoceptors

The effect of methanol extract of P. americana seeds on isolated ileal smooth muscle was studied for isometric response using 10 adult rabbits of both sexes. Reactivity and agonist-antagonist responses of rabbit ileum to the extract were determined in this study. The affinity, effective concentration to give 50% response (EC50) and maximum response were calculated from the concentration response curves (CRC) obtained. The result for the reactivity study showed the seed extract of P. americana caused concentration dependent relaxation of isolated rabbit ileum with threshold responses at concentration of 1×10−9 mg/ml and 120 mg/ml respectively. The extract-antagonist study showed an upward and right shift in CRC in the presence of phenoxybenzamine, a non-selective adrenergic antagonist, with the EC50 increased from 5.01 mg/ml to 12.59 mg/ml and affinity decreased from 0.20 to 0.08. Extract-antagonist study also showed a right and upward shift in the CRC with a greater magnitude in the presence of prazosin, an α1-adrenergic antagonist, with EC50 increased from 0.32 mg/ml to 25.12 mg/ml and a consequential decrease in the affinity from 3.13 to 0.04. In the presence of propranolol, a β-adrenergic antagonist, a downward and left shift in the CRC was observed with the EC50 and PA2 remaining constant at 0.1 mg/ml and 10 respectively. P. americana concentration-dependently reduced or inhibited gastric motility, increasing transit time which is important for food absorption, thus a pro-nutritive and antispasmodic effect. The interaction with α1-adrenoceptors is beneficially in heart failure management. The plant can be developed as a drug candidate for management of hypertension.

A virtual experiment improved students’ understanding of physiological experimental processes ahead of a live inquiry-based practical class

Physiology is commonly taught through direct experience and observation of scientific phenomena in “hands-on” practical laboratory classes. The value of such classes is limited by students’ lack of understanding of the underlying theoretical concepts and their lack of confidence with the experimental techniques. In our experience, students follow experimental steps as if following a recipe, without giving thought to the underlying theory and the relationship between the experimental procedure and the research hypotheses. To address this issue, and to enhance student learning, we developed an online virtual experiment for students to complete before an inquiry-based practical. The virtual experiment and “live” practical laboratory were an investigation of how autonomic nerves control contractions in the isolated rabbit ileum. We hypothesized that the virtual experiment would support students’ understanding of the physiological concepts, as well as the experimental design associated with the practical. Anonymous survey data and usage analytics showed that most students engaged with the virtual experiment. Students thought that it helped them to understand the practical physiological concepts and experimental design, with self-reported time spent on the virtual experiment (and not on lectures or practical class notes) a significant predictor of their understanding. This novel finding provides evidence that virtual experiments can contribute to students’ research skills development. Our results indicate that self-paced online virtual experiments are an effective way to enhance student understanding of physiological concepts and experimental processes, allowing for a more realistic experience of the scientific method and a more effective use of time in practical classes.

Comparing the effect of intestinal bacteria from rabbit, pig, and chicken on inflammatory response in cultured rabbit crypt and villus

Rabbit is susceptible to intestinal infection, which often results in severe inflammatory response. To investigate whether the special community structure of rabbit intestinal bacteria contributes to this susceptibility, we compared the inflammatory responses of isolated rabbit crypt and villus to heat-treated total bacteria in pig, chicken, and rabbit ileal contents. The dominant phylum in pig and chicken ileum was Firmicutes, while Bacteroidetes was dominant in rabbit ileum. The intestinal bacteria from rabbit induced higher expression of toll-like receptor 4 (TLR4) in rabbit crypt and villus (P < 0.05). TLR2 and TLR3 expression was obviously stimulated by chicken and pig intestinal bacteria (P < 0.05) but not by those of rabbit. The ileal bacteria from those three animals all increased the expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in crypts and villus (P < 0.05). Chicken and pig ileal bacteria also stimulated the expression of anti-inflammatory factors interferon beta (IFN-β) and IL-10 (P < 0.05), while those of rabbit did not (P > 0.05). In conclusion, a higher abundance of Gram-negative bacteria in rabbit ileum did not lead to more expressive pro-inflammatory cytokines in isolated rabbit crypt and villus, but a higher percentage of Lactobacillus in chicken ileum might result in more expressive anti-inflammatory factors.

The lipopolysaccharide from Escherichia coli O127:B8 induces inflammation and motility disturbances in rabbit ileum

<p>The aim of this work was to evaluate the effects of lipopolysaccharide (LPS) from <em>Escherichia coli </em>O127:B8 on the expression of toll-like receptor 4 (TLR4), the histology, and motor function in rabbit ileum. Rabbits were injected intravenously with saline or LPS (100 μg/kg, 2 h). The mRNA expression and localization of TLR4 were determined by reverse transcriptase-PCR and immunofluorescence, respectively. Histological damage induced by LPS was evaluated in sections of ileum stained with haematoxylin and eosin. Contractility studies of ileum were performed in an organ bath. The mRNA expression of TLR4 decreased in the muscular but not in the mucosal layer of rabbits treated with LPS. TLR4 was localised in both the mucosal and muscular layers of rabbit ileum. LPS induced intestinal inflammation and altered the spontaneous contractions and the serotonin-, acetylcholine- and KCl-induced contractions. In conclusion, LPS from <em>E. coli </em>O127:B8 induced a decrease in the mRNA expression of TLR4, an inflammatory response, and changes in the contractility of rabbit ileum.</p>