Evaluation of antimotility effect of Lantana camara L. var. acuelata constituents on neostigmine induced gastrointestinal transit in mice

BACKGROUND: Lantana camara L. (Verbenaceae), a widely growing shrub which is toxic to some animal species, has been used in the traditional medicine for treating many ailments. The purpose of the present study was to evaluate the antimotility effects of Lantana camara leaf constituents in mice intestine. METHODS: Evaluation of antimotility activity was done in intestine of mice treated with Lantana camara leaf powder, Lantana camara methanolic extract (LCME), lantadene A, neostigmine and neostigmine + LCME. Neostigmine was used as a promotility agent. Intestinal motility was assessed by charcoal meal test and gastrointestinal transit rate was expressed as the percentage of the distance traversed by the charcoal divided by the total length of the small intestine. The antidiarrheal effect of LCME was studied against castor oil induced diarrhea model in mice. RESULTS: The intestinal transit with LCME at a dose of 500 mg/kg was 26.46% whereas the higher dose (1 g/kg) completely inhibited the transit of charcoal in normal mice. The % intestinal transit in the neostigmine pretreated groups was 24 and 11 at the same doses respectively. When the plant extracts at 125 and 250 mg/kg doses were administered intraperitonealy, there was significant reduction in fecal output compared with castor oil treated mice. At higher doses (500 and 1000 mg/kg), the fecal output was almost completely stopped. CONCLUSION: The remarkable antimotility effect of Lantana camara methanolic extract against neostigmine as promotility agent points towards an anticholinergic effect due to Lantana camara constituents and attests to its possible utility in secretory and functional diarrheas and other gastrointestinal disorders. This effect was further confirmed by significant inhibition of castor oil induced diarrhea in mice by various doses of LCME

Intestinal Electric Stimulation Accelerates Whole Gut Transit and Promotes Fat Excrement in Conscious Rats

*_Introduction:_* Intestinal electric stimulation (IES) is proposed as a potential tool for the treatment of morbid obesity. Our previous study showed that IES with one pair of electrodes accelerated intestinal transit and decreased fat absorption in a segment of the jejunum in the anesthetized rats. The aims of this study were to assess the effects of IES on the whole gut transit and fat absorption in conscious rats, to examine the effects of multi-channel IES, and to explore the cholinergic mechanism behind the effects of IES. 
*_Methods:_* Thirty-eight male rats implanted with serosal electrodes were randomized into five groups: control without IES, 2/3 channel IES with short pulses, atropine and atropine plus IES. The whole gut transit and fat remained and emptied from the gut were analyzed after continuous 2-hour IES. 
*_Results:_* Two and three channel IES significantly accelerated phenol red (marker used for transit) excretion (ANOVA, P < 0.001). No significant difference was found between two and three channel IES. Two channel IES significantly increased the excretion of fat (P < 0.05). Atropine significantly blocked the accelerated transit induced by IES (ANOVA, P < 0.001). Correlation was found between the percentage of phenol red and fat retained in the whole gut (r = 0.497, P < 0.01). 
*_Conclusions:_* IES accelerates whole gut transit and promotes fat excrement in conscious rats, and these effects are mediated through the cholinergic nerves. These findings are in support of the concept that IES may be a promising treatment option for obesity

The intestinal expulsion of the roundworm Ascaris suum is associated with eosinophils, intra-epithelial T cells and decreased intestinal transit time

Ascaris lumbricoides remains the most common endoparasite in humans, yet there is still very little information available about the immunological principles of protection, especially those directed against larval stages. Due to the natural host-parasite relationship, pigs infected with A. suum make an excellent model to study the mechanisms of protection against this nematode. In pigs, a self-cure reaction eliminates most larvae from the small intestine between 14 and 21 days post infection. In this study, we investigated the mucosal immune response leading to the expulsion of A. suum and the contribution of the hepato-tracheal migration. Self-cure was independent of previous passage through the liver or lungs, as infection with lung stage larvae did not impair self-cure. When animals were infected with 14-day-old intestinal larvae, the larvae were being driven distally in the small intestine around 7 days post infection but by 18 days post infection they re-inhabited the proximal part of the small intestine, indicating that more developed larvae can counter the expulsion mechanism. Self-cure was consistently associated with eosinophilia and intra-epithelial T cells in the jejunum. Furthermore, we identified increased gut movement as a possible mechanism of self-cure as the small intestinal transit time was markedly decreased at the time of expulsion of the worms. Taken together, these results shed new light on the mechanisms of self-cure that occur during A. suum infections

A Wireless Implantable System for Facilitating Gastrointestinal Motility.

Gastrointestinal (GI) electrical stimulation has been shown in several studies to be a potential treatment option for GI motility disorders. Despite the promising preliminary research progress, however, its clinical applicability and usability are still unknown and limited due to the lack of a miniaturized versatile implantable stimulator supporting the investigation of effective stimulation patterns for facilitating GI dysmotility. In this paper, we present a wireless implantable GI modulation system to fill this technology gap. The system consists of a wireless extraluminal gastrointestinal modulation device (EGMD) performing GI electrical stimulation, and a rendezvous device (RD) and a custom-made graphical user interface (GUI) outside the body to wirelessly power and configure the EGMD to provide the desired stimuli for modulating GI smooth muscle activities. The system prototype was validated in bench-top and in vivo tests. The GI modulation system demonstrated its potential for facilitating intestinal transit in the preliminary in vivo chronic study using porcine models

In Silico Analysis Identifies Intestinal Transit as a Key Determinant of Systemic Bile Acid Metabolism

Bile acids fulfill a variety of metabolic functions including regulation of glucose and lipid metabolism. Since changes of bile acid metabolism accompany obesity, Type 2 Diabetes Mellitus and bariatric surgery, there is great interest in their role in metabolic health. Here, we developed a mathematical model of systemic bile acid metabolism, and subsequently performed in silico analyses to gain quantitative insight into the factors determining plasma bile acid measurements. Intestinal transit was found to have a surprisingly central role in plasma bile acid appearance, as was evidenced by both the necessity of detailed intestinal transit functions for a physiological description of bile acid metabolism as well as the importance of the intestinal transit parameters in determining plasma measurements. The central role of intestinal transit is further highlighted by the dependency of the early phase of the dynamic response of plasma bile acids after a meal to intestinal propulsion

The Brain-Gut-Microbiome Axis.

Preclinical and clinical studies have shown bidirectional interactions within the brain-gut-microbiome axis. Gut microbes communicate to the central nervous system through at least 3 parallel and interacting channels involving nervous, endocrine, and immune signaling mechanisms. The brain can affect the community structure and function of the gut microbiota through the autonomic nervous system, by modulating regional gut motility, intestinal transit and secretion, and gut permeability, and potentially through the luminal secretion of hormones that directly modulate microbial gene expression. A systems biological model is proposed that posits circular communication loops amid the brain, gut, and gut microbiome, and in which perturbation at any level can propagate dysregulation throughout the circuit. A series of largely preclinical observations implicates alterations in brain-gut-microbiome communication in the pathogenesis and pathophysiology of irritable bowel syndrome, obesity, and several psychiatric and neurologic disorders. Continued research holds the promise of identifying novel therapeutic targets and developing treatment strategies to address some of the most debilitating, costly, and poorly understood diseases

Transit times through the cycle phases of jejunal crypt cells of the mouse

Mean transit times as well as variances of the transit times through the individual phases of the cell cycle have been determined for the crypt epithelial cells of the jejunum of the mouse. To achieve this the fraction of labelled mitoses (FLM) technique has been modified by double labelling with [3H] and [14C]thymidine. Mice were given a first injection of [3H]thymidine, and 2 hr later a second injection of [14C]thymidine. This produces a narrow subpopulation of purely 3H-labelled cells at the beginning of G2-phase and a corresponding subpopulation of purely 14C-labelled cells at the beginning of the S-phase. When these two subpopulations progress through the cell cycle, one obtains FLM waves of purely 3H- and purely 14C-labelled mitoses. These waves have considerably better resolution than the conventional FLM-curves. From the temporal positions of the observed maxima the mean transit times of the cells through the individual phases of the cycle can be determined. Moreover one obtains from the width of the individual waves the variances of the transit times through the individual phases. It has been found, that the variances of the transit times through successive phases are additive. This indicates that the transit times of cells through successive phases are independently distributed. This statistical independence is an implicit assumption in most of the models applied to the analysis of FLM curves, however there had previously been no experimental support of this assumption. A further result is, that the variance of the transit time through any phase of the cycle is proportional to the mean transit time. This implies that the progress of the crypt epithelial cells is subject to an equal degree of randomness in the various phases of the cycle

Toll-Like Receptor 4 Modulates Small Intestine Neuromuscular Function through Nitrergic and Purinergic Pathways

Objective: Toll-like receptors (TLRs) play a pivotal role in the homeostatic microflora-host crosstalk. TLR4-mediated modulation of both motility and enteric neuronal survival has been reported mainly for colon with limited information on the role of TLR4 in tuning structural and functional integrity of enteric nervous system (ENS) and in controlling small bowel motility. Methods: Male TLR4 knockout (TLR4-/-, 9 \ub1 1 weeks old) and sex- and age-matched wild-type (WT) C57BL/6J mice were used for the experiments. Alterations in ENS morphology and neurochemical code were assessed by immunohistochemistry whereas neuromuscular function was evaluated by isometric mechanical activity of ileal preparations following receptor and non-receptor-mediated stimuli and by gastrointestinal transit. Results: The absence of TLR4 induced gliosis and reduced the total number of neurons, mainly nNOS+ neurons, in ileal myenteric plexus. Furthermore, a lower cholinergic excitatory response with an increased inhibitory neurotransmission was found together with a delayed gastrointestinal transit. These changes were dependent on increased ileal non-adrenergic non-cholinergic (NANC) relaxations mediated by a complex neuronal-glia signaling constituted by P2X7 and P2Y1 receptors, and NO produced by nNOS and iNOS. Conclusion: We provide novel evidence that TLR4 signaling is involved in the fine-tuning of P2 receptors controlling ileal contractility, ENS cell distribution, and inhibitory NANC neurotransmission via the combined action of NO and adenosine-5\u2032-triphosphate (ATP). For the first time, this study implicates TLR4 at regulating the crosstalk between glia and neurons in small intestine and helps to define its role in gastrointestinal motor abnormalities during dysbiosis

Surgeon\u27s perspective on short bowel syndrome: Where are we?

Short bowel syndrome (SBS) is due to a massive loss of small bowel: the reduction of gut function is below the minimum necessary to maintain health (in adults) and growth (in children) so intravenous supplementation is required. Parenteral nutrition represents the milestone of treatment and surgical attempts should be limited only when the residual bowel is sufficient to increase absorption, reducing diarrhea and slowing the transit time of nutrients, water and electrolytes. The surgical techniques lengthen the bowel (tapering it) or reverse a segment of it: developed in children, nowadays are popular also among adults. The issue is mainly represented by the residual length of the small bowel where ileum has shown increased adaptive function than jejunum, but colon should be considered because of its importance in the digestive process. These concepts have been translated also in intestinal transplantation, where a colonic graft is nowadays widely used and the terminal ileum is the selected segment for a living-related donation. The whole replacement by a bowel or multivisceral transplant is still affected by poor long term outcome and must be reserved to a select population of SBS patients, affected by intestinal failure associated with irreversible complications of parenteral nutrition

Effects of Clostridium perfringens iota toxin in the small intestine of mice

Iota toxin is a binary toxin solely produced by Clostridium perfringens type E strains, and is structurally related to CDT from C. difficile and CST from C. spiroforme. As type E causes hemorrhagic enteritis in cattle, it is usually assumed that associated diseases are mediated by iota toxin, although evidence in this regard has not been provided. In the present report, iota toxin intestinal effects were evaluated in vivo using a mouse model. Histological damage was observed in ileal loops treated with purified iota toxin after 4 h of incubation. Luminal iota toxin induced fluid accumulation in the small intestine in a dose dependent manner, as determined by the enteropooling and the intestinal loop assays. None of these changes were observed in the large intestine. These results suggest that C. perfringens iota toxin alters intestinal permeability, predominantly by inducing necrosis and degenerative changes in the mucosal epithelium of the small intestine, as well as changes in intestinal motility. The obtained results suggest a central role for iota toxin in the pathogenesis of C. perfringens type E hemorrhagic enteritis, and contribute to remark the importance of clostridial binary toxins in digestive diseases.Fil: Redondo, Leandro Martin. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Redondo, Enzo Alejandro. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dailoff, Gabriela Cecilia. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Leiva, Carlos Leónidas. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Díaz Carrasco, Juan María. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bruzzone, Octavio Augusto. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cangelosi, Adriana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; ArgentinaFil: Geoghegan, Patricia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; ArgentinaFil: Fernandez Miyakawa, Mariano Enrique. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin