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Background: BALB/c and C57BL/6 mice are widely used in biomedical research; however, the differences between strains are still underestimated. Our aims were to develop an experimental protocol to evaluate the duodenal contractility and gastrointestinal transit in mice using the Alternating Current Biosusceptometry (ACB) technique and to compare gastrointestinal motor function and morphology between BALB/c and C57BL/6 strains. Methods: Male mice were used in experiments (a) duodenal contractility: animals which had a magnetic marker surgically fixed in the duodenum to determine the frequency and amplitude of contractions and (b) gastrointestinal transit: animals which ingested a magnetically marked chow to calculate the Oro-Anal Transit Time (OATT) and the Fecal Pellet Elimination Rate (FPER). The animals were killed after the experiments for organ collection and morphometric analysis.Key Results: BALB/c and C57BL/6 had two different duodenal frequencies (high and low) with similar amplitudes. After 10 hours of monitoring, BALB/c eliminated around 89% of the ingested marker and C57BL/6 eliminated 33%; OATT and FPER were slower for C57BL/6 compared with BALB/c. The OATT and amplitude of low frequency had a strong positive correlation in C57BL/6. For BALB/c, the gastric muscular layer was thicker compared to that measured for C57BL/6. Conclusions and Inferences:The experimental protocol to evaluate duodenal contractility and fecal magnetic pellets output using the ACB technique in mice was successfully established. BALB/c strains had higher duodenal frequencies and a shorter time to eliminate the ingested marker. Our results showed differences in both motor function and gastrointestinal morphology between BALB/c and C57BL/6 strains. K E Y W O R D S BALB/c, C57BL/6, duodenal contractility, gastrointestinal transit, inbred S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section.

What is the central question of this study? The aim was to propose an animal model for investigating the effects of immunosuppressive monotherapy on gastrointestinal motility using a non-invasive biomagnetic technique. What is main finding and its importance? In our experimental study, immunosuppressive drugs currently in use accelerated gastric emptying whilst increasing the frequency and amplitude of gastric contractions after treatment, except for Mycophenolate and azathioprine. Alternating current biosusceptometry is a useful tool to evaluate side-effects of drugs on the gastrointestinal tract, which will help in understanding the symptoms and improving clinical management of patients. The aim was to propose an animal model for investigating the effects of immunosuppressive monotherapy on gastrointestinal motility using a non-invasive biomagnetic technique. Male Wistar rats were randomly distributed into the following treatment groups: ciclosporin, tacrolimus, prednisone, sirolimus, mycophenolate mofetil, everolimus, azathioprine and control. Each animal was treated for 14 days by gavage with dosages ranging from 1 to 20 mg kg day considering the area-to-volume ratio and hepatic metabolism. Gastrointestinal transit and gastric contractility measurements were evaluated by alternating current biosusceptometry before and after treatment. Gastric emptying was faster in animals treated with tacrolimus, prednisone, sirolimus and everolimus compared with control animals (126.7 ± 12.7 min). There was a significant increase in the frequency of contractions after ciclosporin, tacrolimus, azathioprine and sirolimus treatment compared with control animals (4.6 ± 0.3 cycles min ). Increases in the amplitude of contraction were observed after treatment with tacrolimus, sirolimus and everolimus compared with control rats (34.9 ± 6.0 dB). The results showed that our animal model was suitable for demonstrating that most immunosuppressive drugs currently in use impaired at least one gastrointestinal motility parameter. As a non-invasive technique, alternating current biosusceptometry is a potentially useful tool for evaluation of side-effects of drugs in gastrointestinal tract, helping us to understand the symptoms to improve clinical management of patients.

The aim was to correlate the gastrointestinal transit profile in rats, evaluated by a biomagnetic technique, in response to infection with different loads of Strongyloides venezuelensis. Eggs per gram, intestinal number of worms and fecundity, and also gastric emptying time, cecum arrival time, small intestinal transit time and stool weight were determined. Assessments occurred at 0 (control), 3, 6, 9, 12, 15, 18 and 21 days post infection (dpi) with three infective loads (400, 2000, and 10,000 L). Gastric emptying was faster (p=0.0001) and the intestinal transit was significantly slower (p=0.001) during the infection time course. Also, linear mixed-effects models showed significantly changes in small intestinal transit after three parasite load over time. Cecum arrival was not influenced by infection time course or parasite load. As indirect effect, stool weight decreased accompanied a strong oviposition peak at 9 dpi in 400 L and 2000 L. In several motor function instances, neuromuscular dysfunction persists after mucosal inflammation has decreased. Our approach could be very helpful to evaluate gastrointestinal motor abnormalities in vivo after parasite infection. Despite parasitological data progressively decreased after 15 dpi, small intestinal transit worse over time and according to burden.

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Our aim was to verify the effects of prednisone related to gastrointestinal motility, intestinal histology, and mucosal mast cells in rats. Two-month-old male Wistar rats were randomly assigned to control group (vehicle) animals receiving saline 0.9% (n = 7) or treated orally with 0.625 mg/kg/day of prednisone (n = 7) or 2.5 mg/kg/day of prednisone (n = 7) during 15 days. Mast cells and other histologic analyses were performed in order to correlate to gastric emptying, cecum arrival, and small intestine transit evaluated by Alternating Current Biosusceptometry. Results showed that prednisone in adult rats increased the frequency of gastric contractions, hastened gastric emptying, slowed small intestinal transit, and reduced mucosal mast cells. Histologically, the treatment with both doses of prednisone decreased villus height, whereas longitudinal and circular muscles and crypt depth were not affected. These findings indicate an impairment of intestinal absorption which may be linked to several GI dysfunctions and symptoms. The relationship between gastrointestinal motor disorders and cellular immunity needs to be clarified in experimental studies since prednisone is one of the most prescribed glucocorticoids worldwide.

Background: Triple immunosuppressive therapy is associated with several gastrointestinal disorders. The aim of this study was to investigate the effects induced by the triple immunosuppressive therapy on the gastrointestinal tract of rats. Methods: Male Wistar rats were randomly assigned into three experimental groups: Control: filtered water; TAC+MPS+PRED: treated with Tacrolimus plus Mycophenolate Sodium plus Prednisone; and CSA+AZA+PRED: treated with Cyclosporine plus Azathioprine plus Prednisone. The treatment was done for 14 days by gavage. Gastric emptying and contractility were evaluated by the Alternating Current Biosusceptometry (ACB) and Electrogastrography (EGG). Histological, biochemical and hematological analysis were also performed. Results: Gastric emptying time was slower in the CSA + AZA + PRED group in comparison with control (p < 0.01) and TAC + MPS + PRED groups (p < 0.001). Animals treated with TAC + MPS + PRED showed accelerated gastric emptying (p<0.05) compared to control. The amplitude of gastric contractions in both immunosuppressed groups was higher than observed in the control. The frequency of gastric contractions for the CSA+AZA+PRED group was also increased (p<0.01). Results obtained by EGG were similar to those recorded with the ACB. The thickness of circular layer from stomach muscle decreased in both immunosuppressed groups, while longitudinal layer was reduced only in the CSA+AZA+PRED group. Conclusion: Triple immunosuppressive therapy alters gastric motility and compromise the muscular layers and the association between CSA, AZA, and PRED provokes the major alterations in structure and gastric function. Specific gastrointestinal side effects resulting from different immunosuppressive therapies still need to be elucidated in order to provide more effective and personalized therapy for patients.

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