Effects of a Single Opioid Dose on Gastrointestinal Motility in Rabbits (Oryctolagus cuniculus): Comparisons among Morphine, Butorphanol, and Tramadol

The aim of this study was to evaluate and compare the effects of single doses of butorphanol, morphine, and tramadol on gastrointestinal motility in rabbits (Oryctolagus cuniculus) using non-invasive imaging methods, such as radiographic barium follow through and ultrasonographic contraction counts. Time-lapse radiographic and ultrasound examinations were performed before and after a single intramuscular dose of 5 mg kg−1 butorphanol, 10 mg kg−1 morphine, or 10 mg kg−1 tramadol. Pyloric and duodenal contraction counts by ultrasonography and radiographic repletion scores for the stomach and caecum were analysed using a mixed linear model. No significant effect was noted on ultrasound examinations of pyloric and duodenal contractions after administration of an opioid treatment. Morphine had a significant effect on the stomach and the caecum repletion scores, whereas butorphanol had a significant effect only on the caecum repletion score. Tramadol had no significant effect on the stomach or caecum repletion scores. The present findings suggest that a single dose of 5 mg kg−1 butorphanol or 10 mg kg−1 morphine temporarily slows gastrointestinal transit in healthy rabbits, preventing physiological progression of the alimentary bolus without the induction of ileus. In contrast, a single dose of 10 mg kg−1 tramadol has no such effects.

Design of Oral Sustained-Release Pellets by Modeling and Simulation Approach to Improve Compliance for Repurposing Sobrerol

Sobrerol, an oral mucolytic agent, in a recent study showed promise for treating multiple sclerosis. A human equivalent dose of 486 mg of sobrerol administered thrice daily (i.e., 1459 mg of daily dose) demonstrated the highest therapeutic efficacy for repurposing use, which also points out the poor compliance of administration. In this study, oral sustained-release pellets of sobrerol were successfully developed with evaluated manufacturing conditions and drug release kinetics. For design of the target drug product, we used a modeling and simulation approach to establish a predictive model of oral pharmacokinetic profile, by exploring the characteristics and correlations corresponding to the pharmacokinetics and pharmacodynamics of sobrerol, such as absorption lag time (0.18 h), time-scaling in vitro–in vivo correlation (tin-vitro = 0.494 tin-vivo − 0.0904), gastrointestinal transit time (8 h), minimum effective concentration (1.61 μg/mL), and duration of action (12.8 h). Results showed that the frequency of administration and the daily dose remarkably reduced by 33.3% (i.e., from thrice to twice daily) and 22.8%, respectively, which indicates that this prototype approach can be adopted for rapidly developing a modified-release dosage form of sobrerol, with improvement of compliance of administration and therapeutic efficacy.

Prophage Activation in the Intestine: Insights Into Functions and Possible Applications

Prophage activation in intestinal environments has been frequently reported to affect host adaptability, pathogen virulence, gut bacterial community composition, and intestinal health. Prophage activation is mostly caused by various stimulators, such as diet, antibiotics, some bacterial metabolites, gastrointestinal transit, inflammatory environment, oxidative stress, and quorum sensing. Moreover, with advancements in biotechnology and the deepening cognition of prophages, prophage activation regulation therapy is currently applied to the treatment of some bacterial intestinal diseases such as Shiga toxin-producing Escherichia coli infection. This review aims to make headway on prophage induction in the intestine, in order to make a better understanding of dynamic changes of prophages, effects of prophage activation on physiological characteristics of bacteria and intestinal health, and subsequently provide guidance on prophage activation regulation therapy.

Evaluation of gastrointestinal transit times and pH in healthy cats using a continuous pH monitoring system

Objectives The aim of this study was to characterize gastrointestinal (GI) transit times and pH in healthy cats. Methods GI transit times and pH were measured in six healthy, colony-housed, purpose-bred spayed female cats using a continuous, non-invasive pH monitoring system in a sequential order design. For the first period (‘pre-feeding’), food was withheld for 20 h, followed by oral administration of a pH capsule. Five hours post-capsule administration, cats were meal-fed by offering them their daily allowance of food for 1 h. For the second period (‘post-feeding’), food was withheld for 24 h and cats were fed for 1 h, after which a pH capsule was orally administered. Studies in both periods were repeated three times. GI transit times and pH were compared between the two periods. Results The median transit times for the pre- and post-feeding periods, respectively, were: gastric –94 mins (range 1–4101) and 1068 mins (range 484–5521); intestinal –1350 mins (range 929–2961) and 1534 mins (range 442–2538); and GI –1732 mins (range 1105–5451) and 2795 mins (range 926–6563). The median GI pH values for the first and second periods, respectively, were: esophageal –7.0 (range 3.5–7.8) and 4.5 (range 2.9–6.4); gastric –2.7 (range 1.7–6.2) and 2.0 (range 1.1–3.3); intestinal –8.2 (range 7.6–8.7) and 7.8 (range 6.7–8.5); first-hour small intestinal –8.2 (range 7.4–8.7) and 8.3 (range 7.9–8.6); and last-hour large intestinal –8.5 (range 7.0–8.9) and 7.8 (range 6.3–8.7). Gastric ( P <0.0020) and intestinal pH ( P <0.0059) were significantly increased in the pre-feeding period compared with the post-feeding period. Conclusions and relevance Gastric and intestinal pH differed significantly when the capsule was administered 5 h prior to feeding compared with 1 h after feeding. Transit times for both periods showed high degrees of intra- and inter-individual variability.

A Novel Multitarget Mu- and Delta-Opioid Receptors Agonist HAGD Has Peripherally Restrictive Potent Analgesia with Less Side Effects in Mice and Minimal Impact on Human Sperm Motility

ObjectivePain is a common clinical symptom. Although a variety of opioid analgesics have been developed, the side effects including negative impact on human sperm motility still hinder their application. Aim of this study is to develop a novel opioid analgesic, a multitarget peptide HAGD (H-Tyr-D-AIa-GIy-Phe-NH2) which has less side effects and minimal impact on sperm motility.MethodsThe peripheral antinociceptive effects of HAGD were appraised in a series of preclinical mice pain models, including the tail-flick test, carrageenan-induced inflammatory pain, acetic acid-induced writhing test and formalin test. In conditioned place preference experiment, open field test, gastrointestinal transit test and rotarod test, the side effects of HAGD in mice were assessed. The impacts of HAGD on sperm motility in vitro were investigated.ResultsHAGD produced equipotent antinociception compared with morphine. HAGD was stronger in terms of analgesia intensity in chemical stimulation pain of formalin test phase I. The antinociception was mediated by mu- and delta-opioid receptors. HAGD didn’t induce conditioned place preference and hyperlocomotion, but morphine did. Both HAGD and morphine had no impacts on motor coordination. HAGD had a limited side effect in gastrointestinal transit, while morphine inhibited gastrointestinal transit to a greater extent. However, HAGD had minimal impact on human sperm motility, whereas morphine declined sperm motility at concentrations of 1 × 10-7 mol/l and 1 × 10-8 mol/l at 3.5 h of incubation.Conclusion HAGD may be a better candidate for future development of novel multitarget opioid analgesics with less side effects and minimal impact on human sperm motility.

Evaluation of Antidiarrheal Activity of 80% Methanolic Extract of the Leaves of Cordia africana (Lamiaceae) in Mice

Background. Diarrheal disease is a major cause of morbidity and mortality throughout the world, particularly in developing countries. Currently available drugs are linked with adverse effects, contraindications, and risk of resistance. Traditionally, the leaf concoction of Cordia africana is claimed to be used for diarrhea. However, the safety and efficacy of the leaf extract have not been scientifically approved yet. Therefore, the study was conducted to validate its antidiarrheal activity and safety profile in mice. Method. The hydromethanolic extract was obtained by the cold maceration technique in 80% methanol. Phytochemical screening tests were done for secondary metabolites by using standard tests. The antidiarrheal activity of the test extract at the doses of 100, 200, and 400 mg/kg was evaluated by using castor oil-induced diarrheal, gastrointestinal transit, and enteropooling models in mice. Result. In an acute toxicity study, there were no visible signs of toxicity and mortality following a single oral administration of 2000 mg/kg. Phytochemical screening tests revealed the presence of alkaloids, saponins, flavonoids, terpenoids, phenols, and tannins. The hydromethanolic extract significantly prolonged the onset of diarrhea and reduced the weight of wet and total feces at 100 ( P < 0.01 ), 200 ( P < 0.001 ), and 400 mg/kg ( P < 0.001 ) in the castor oil-induced diarrheal model. However, in the gastrointestinal transit model, a significant ( P < 0.001 ) reduction in the charcoal meal travel was observed in the middle (200 mg/kg) and higher (400 mg/kg) test doses. Similarly, the extract produced a significant ( P < 0.001 ) reduction in the weight and volume of intestinal contents at the aforementioned doses. Conclusion. The study demonstrated that the test extract showed promising antidiarrheal activity. Hence, this study supports its antidiarrheal use in Ethiopian folklore medicine.

Epidural analgesia is associated with earlier gastrointestinal transit after radical cystectomy but does not reduce the incidence of postoperative ileus: A retrospective cohort study

Objective: To compare the effect of combined epidural thoracic analgesia and general anaesthesia (CEGA) in radical cystectomy (RC) with respect to the return of gastrointestinal passage, the incidence of paralytic postoperative ileus (POI) compared to general anaesthesia (GA) only. Patients and methods: We conducted a retrospective review using the electronic medical records of 236 patients who underwent RCs between July 2011 and September 2018 at the Medical Center – University of Freiburg. Results: A CEGA was administered to 202 patients, while 34 patients received only GA. The baseline characteristics of patients with and without CEGA showed no significant differences. CEGA will decrease the time required for return of gastrointestinal transit as measured by time to first defecation by about 13 hours. In the first 90 days after surgery, 82 (34.7%) patients had a POI. There was no significant difference between complications in the CEGA and GA groups. Conclusion: A CEGA accelerates the return of the gastrointestinal transit but does not reduce the incidence of postoperative ileus. Level of evidence: 2b

Effect of partial substitution of fishmeal with insect meal (Hermetia illucens) on gut neuromuscular function in Gilthead sea bream (Sparus aurata)

Alternative nutrient sources to fishmeal for fish feed, such as insect meals, represent a promising sustainable supply. However, the consequences for fish digestive function have not been exhaustively investigated. In the present study we evaluated the effect of partial fishmeal substitution with 10% Hermetia illucens (Hi10) larvae meal on the neuromuscular function of proximal and distal intestine in gilthead sea bream. In animals fed with insect meal, weight and growth parameters were similar to controls fed with conventional fishmeal. In addition, no anomalies in intestinal gross morphology and no overt signs of inflammation were observed. The gastrointestinal transit was significantly reduced in Hi10 fed animals. In the proximal and distal intestine longitudinal muscle, Hi10 feeding downregulated the excitatory cholinergic and serotoninergic transmission. Sodium nitroprusside-induced inhibitory relaxations increased in the proximal intestine and decreased in the distal intestine after Hi10 meal. Changes in the excitatory and inhibitory components of peristalsis were associated with adaptive changes in the chemical coding of both proximal and distal intestine myenteric plexus. However, these neuromuscular function alterations were not associated with considerable variations in morphometric growth parameters, suggesting that 10% Hi meal may represent a tolerable alternative protein source for gilthead sea bream diets.