Growth hormone alters gross anatomy and morphology of the small and large intestines in age- and sex-dependent manners.

PURPOSE: Growth hormone (GH) has an important role in intestinal barrier function, and abnormalities in GH action have been associated with intestinal complications. Yet, the impact of altered GH on intestinal gross anatomy and morphology remains unclear. METHODS: This study investigated the influence of GH signaling on gross anatomy, morphology, and fibrosis by characterizing the small and large intestines in male and female bovine growth hormone transgenic (bGH) mice and GH receptor gene-disrupted (GHR-/-) mice at multiple timepoints. RESULTS: The length, weight, and circumference of the small and large intestines were increased in bGH mice and decreased in GHR-/- mice across all ages. Colon circumference was significantly increased in bGH mice in a sex-dependent manner while significantly decreased in male GHR-/- mice. Villus height, crypt depth, and muscle thickness of the small intestine were generally increased in bGH mice and decreased in GHR-/- mice compared to controls with age- and sex-dependent exceptions. Colonic crypt depth and muscle thickness in bGH and GHR-/- mice were significantly altered in an age- and sex-dependent manner. Fibrosis was increased in the small intestine of bGH males at 4 months of age, but no significant differences were seen between genotypes at other timepoints. CONCLUSION: This study observed notable opposing findings in the intestinal phenotype between mouse lines with GH action positively associated with intestinal gross anatomy (i.e. length, weight, and circumference). Moreover, GH action appears to alter morphology of the small and large intestines in an age- and sex-dependent manner.

Anatomy, physiology, and updates on the clinical management of constipation.

Clinical management of constipation has evolved from the prescription of dietary supplements, to potent stimulant laxatives, to corrective surgeries for organic blockage. Yet constipation does not respond to a one-size-fits-all treatment. In recent decades, the Bristol Stool Form Scale and Rome III diagnostic criteria have allowed for algorithmic diagnosis, yet these criteria could benefit from further extension and meaningful discussion. This review incorporates pertinent clinical updates and uses the anatomy and physiology of constipation as helpful signposts for the practicing clinician.

Pattern selection in growing tubular tissues.

Tubular organs display a wide variety of surface morphologies including circumferential and longitudinal folds, square and hexagonal undulations, and finger-type protrusions. Surface morphology is closely correlated to tissue function and serves as a clinical indicator for physiological and pathological conditions, but the regulators of surface morphology remain poorly understood. Here, we explore the role of geometry and elasticity on the formation of surface patterns. We establish morphological phase diagrams for patterns selection and show that increasing the thickness or stiffness ratio between the outer and inner tubular layers induces a gradual transition from circumferential to longitudinal folding. Our results suggest that physical forces act as regulators during organogenesis and give rise to the characteristic circular folds in the esophagus, the longitudinal folds in the valves of Kerckring, the surface networks in villi, and the crypts in the large intestine.

Distribution of arterial supply to the large intestine in the anteater (Tamandua tetradactyla).

The blood supply in the large intestine of seven specimens of the lesser anteater, Tamandua tetradactyla, studied. The method included preparation of the macroscopic collection report, perfusion of the arterial network with water, injection of colored latex, fixation in formaldehyde, and preservation in ethanol. For our description and analyses, we performed dissections under mesoscopic light and made photo documentation of our observations. The large intestine of T. tetradactyla is irrigated by the caudal mesenteric artery (rectum, left colic fold, descending colon and transverse colon) and cranial mesenteric artery (right colic fold, cecal pouch). We observed that the large intestine in these animals is implied in the abdominal wall without becoming affixed to the wall, or developing adhesions on individual segments. The caudal mesenteric artery feeds the straight collateral branches (primary, secondary, and tertiary) and a few juxtacolic arched branches (first and second order). The straight branches emerge from the arched branches, bifurcate, and embrace the intestinal loop to irrigate it. The presence of anastomoses between the CaMA and the CrMA apparently ensures a relatively stable flow in the event of failure of either. This is very important, as the peritoneum in this species is completely dependent on blood from these two arteries. The model of vascularization and fixation of the large intestine into the abdominal wall of T. tetradactyla is different from that in other vertebrates.

The small and large intestine contain related mesenchymal subsets that derive from embryonic Gli1+ precursors.

The intestinal lamina propria contains a diverse network of fibroblasts that provide key support functions to cells within their local environment. Despite this, our understanding of the diversity, location and ontogeny of fibroblasts within and along the length of the intestine remains incomplete. Here we show that the small and large intestinal lamina propria contain similar fibroblast subsets that locate in specific anatomical niches. Nevertheless, we find that the transcriptional profile of similar fibroblast subsets differs markedly between the small intestine and colon suggesting region specific functions. We perform in vivo transplantation and lineage-tracing experiments to demonstrate that adult intestinal fibroblast subsets, smooth muscle cells and pericytes derive from Gli1-expressing precursors present in embryonic day 12.5 intestine. Trajectory analysis of single cell RNA-seq datasets of E12.5 and adult mesenchymal cells suggest that adult smooth muscle cells and fibroblasts derive from distinct embryonic intermediates and that adult fibroblast subsets develop in a linear trajectory from CD81+ fibroblasts. Finally, we provide evidence that colonic subepithelial PDGFRαhi fibroblasts comprise several functionally distinct populations that originate from an Fgfr2-expressing fibroblast intermediate. Our results provide insights into intestinal stromal cell diversity, location, function, and ontogeny, with implications for intestinal development and homeostasis.

[Creation of models of incomplete external lip-like large bowel fistula in experiment].

The method of experimental simulation of the incomplete external lip-like large bowel fistula creation was elaborated on experimental animals for studying of possibilities forapplication of hyperthermic methods of the fistula channel obliteration and disinfectioning of the neighboring anterior abdominal wall tissues. There were studied up microflora and bacterial seeding of the large bowel contents in the zone of a fistula exit as well as dynamics of changes of inflammatory processes, occurring in tissues of anterior abdominal wall, neighboring the external orifice of a fistula channel.

Morphometric characteristics of the small and large intestines of Mus musculus during postnatal development.

The objective of this study was to investigate the size of the small and large intestine in postnatal development of Mus musculus mice. The gut was obtained from 2-, 4-, 6-, and 12-week-old animals. The morphometric analysis was performed at microscopic level. Measurements and calculations included dimensions of villi (height, diameter) and their number per 1 mm(2) surface area in the proximal, middle, and distal section of the small intestine, as well as the length and surface area (external and internal) of the small and large intestines. To find the allometric relationship between the size of the small and large intestines and body mass, reduced major axis regression was applied. The length and surface area of both intestinal segments gradually increased with age. The increase in the internal surface area of the small intestine was the result of lengthening of the intestine and increasing diameter of the villi in its proximal and middle sections. No increase in villus height during the studied period was detected. A marked increase in the size of the intestinal segments was observed between the 2(nd) and 4(th) weeks of life, when the length doubled and the surface area tripled in size. Allometric analysis revealed that the increase in length and internal surface area of the small and large intestines was more rapid than the body mass increase during the weaning period, while it was not different from isometry after the weaning. In conclusion, the greatest changes in the structure and size of the small and large intestines of mice occurred in the weaning period. During this period these two segments of intestine grew faster than the rest of the body and reached adult proportions.

Less need for differentiation? Intestinal length of reptiles as compared to mammals.

Although relationships between intestinal morphology between trophic groups in reptiles are widely assumed and represent a cornerstone of ecomorphological narratives, few comparative approaches actually tested this hypothesis on a larger scale. We collected data on lengths of intestinal sections of 205 reptile species for which either body mass (BM), snout-vent-length (SVL) or carapax length (CL) was recorded, transforming SVL or CL into BM if the latter was not given, and analyzed scaling patterns with BM and SVL, accounting for phylogeny, comparing three trophic guilds (faunivores, omnivores, herbivores), and comparing with a mammal dataset. Length-BM relationships in reptiles were stronger for the small than the large intestine, suggesting that for the latter, additional factors might be relevant. Adding trophic level did not consistently improve model fit; only when controlling for phylogeny, models indicated a longer large intestine in herbivores, due to a corresponding pattern in lizards. Trophic level effects were highly susceptible to sample sizes, and not considered strong. Models that linked BM to intestine length had better support than models using SVL, due to the deviating body shape of snakes. At comparable BM, reptiles had shorter intestines than mammals. While the latter finding corresponds to findings of lower tissue masses for the digestive tract and other organs in reptiles as well as our understanding of differences in energetic requirements between the classes, they raise the hitherto unanswered question what it is that reptiles of similar BM have more than mammals. A lesser effect of trophic level on intestine lengths in reptiles compared to mammals may stem from lesser selective pressures on differentiation between trophic guilds, related to the generally lower food intake and different movement patterns of reptiles, which may not similarly escalate evolutionary arms races tuned to optimal agility as between mammalian predators and prey.

Microvascular anatomy of the large intestine in adult Xenopus laevis: scanning electron microscopy of vascular corrosion casts and correlative light microscopy.

The microvascular anatomy of the large intestine of the adult South African Clawed Toad, Xenopus laevis (Daudin), was studied by scanning electron microscopy (SEM) of vascular corrosion casts (VCCs) and correlative light microscopy. Observations showed the large intestine to be supplied by the haemorrhoidal artery and the posterior mesenteric artery and drain via the posterior haemorrhoidal vein into either the left or right posterior abdominal vein. Both arteries and veins showed a bipinnate supply/draining pattern with branches running circumferentially. Vessels embraced the gut wall while arteries and veins in most cases alternated along the gut length. Many short terminal arterioles arose from the circumferential arteries at almost acute angles and capillarized after a short distance. Capillary lengths were short and continued into numerous postcapillary venules which merged either in a leaf vein-like formation or in a rosette-like formation with up to four draining sites per supplying arteriole. The microvasculature was found to be well adapted 1) to sustain blood flow under different amounts of feces in the gut and 2) to provide optimal conditions for the resorption of water and salts from the gut lumen into the blood vascular system by the high number of venules and their conspiciouos rosette-like and leaf vein-like patterns.

Conservative management of faecal incontinence in adults.

While faecal incontinence is a common problem, many people may be embarrassed to admit having the condition. An understanding of the various factors that contribute to faecal incontinence can increase nurses' awareness of potential continence problems. Nurses can assess patients for faecal incontinence, provide valuable information and implement a range of management strategies to support patients and improve their quality of life. This article explains the reasons for incontinence, outlines comprehensive patient assessment and discusses the various treatment options to help patients overcome or manage the problem. The author describes the role of continence advisers and clinical nurse specialists who can offer additional expertise.

Crypts are the site of intestinal fluid and electrolyte secretion.

The site of adenosine 3',5'-monophosphate-mediated fluid and electrolyte secretion across mammalian large intestine was found to be the crypts of Lieberkühn by means of two techniques. First, the formation of fluid droplets was visualized on the oil-covered mucosal surface directly over crypt duct openings when secretion was stimulated. Second, microelectrode impalement of individual surface and crypt cells revealed that only crypts cells produced a pattern of secretagogue induced alterations in membrane potential and resistance that was characteristic of secretory epithelia.

Interactive and individual effects of dietary non-digestible carbohydrates and oils on DNA damage, SCFA and bacteria in the large bowel of rats.

Dietary non-digestible carbohydrates (NDC) play an important role in large-bowel health and one form of NDC, resistant starch (RS), can promote low levels of DNA damage and other markers of colonic health. The objective of the present study was to determine whether the ability of dietary RS or other NDC to influence colonic health, particularly DNA damage, is dependent on the type of dietary oil. We compared the effects of diets containing 10 % of NDC from cellulose, wheat bran, high-amylose maize starch (HAS, a rich source of RS type 2) or a retrograded HAS (RHAS, a rich source of RS type 3) on DNA damage, SCFA production and bacterial changes in the large bowel of rats. Each carbohydrate source was combined with 10 % fish oil (FO) or Sunola oil (SO; rich in oleic acid). There was a significant interaction between NDC and oil treatments on single-strand DNA breaks in colonocytes isolated from the colon. The damage in rats consuming RHAS was greater for FO consumption than for SO consumption. There was a significant interaction between NDC and oils on caecum weights and treatment effects of NDC and oils were observed for the weights and lengths of other gut tissues. Significant differences were found in colonic SCFA pools and caecal numbers of lactobacilli, bifidobacteria, Escherichia coli and Bacteroides fragilis with the various NDC and oil treatments. The present results demonstrate that the effects of NDC and oils, particularly on colonic DNA damage, can depend on how they are combined within the diet.

Wall thickness and mucous cell distribution in the rabbit large intestine.

To achieve a better understanding of rabbit large intestinal functions, such as production of hard and soft feces and cecal fermentation, knowledge of the intestinal wall structure is essential. However, such knowledge is far from complete. Therefore, the aims of this study were to measure the thickness of the wall and its constituent layers and describe distribution of mucous cells in each segment of the large intestine in New Zealand White rabbits. Results showed that the cecum had the thinnest entire wall throughout the large intestine, and the fusus coli and rectum had a thicker entire wall in comparison to the cecum, the first segment of the proximal colon, the second segment of the proximal colon, and the distal colon. Moreover, the thickness of the mucosa in the fusus coli and that of the inner and outer layers of the tunica muscularis in the rectum were greater than that of the other segments. Mucous cells in the mucosa were the fewest in the cecum and most numerous in the fusus coli. This study provides detailed knowledge of the wall thickness and distribution of mucous cells in the large intestine of the rabbit. These findings are important for improving our understanding of rabbit intestinal physiology and pathology.

Regional complexity in enteric neuron wiring reflects diversity of motility patterns in the mouse large intestine.

The enteric nervous system controls a variety of gastrointestinal functions including intestinal motility. The minimal neuronal circuit necessary to direct peristalsis is well-characterized but several intestinal regions display also other motility patterns for which the underlying circuits and connectivity schemes that coordinate the transition between those patterns are poorly understood. We investigated whether in regions with a richer palette of motility patterns, the underlying nerve circuits reflect this complexity. Using Ca2+ imaging, we determined the location and response fingerprint of large populations of enteric neurons upon focal network stimulation. Complemented by neuronal tracing and volumetric reconstructions of synaptic contacts, this shows that the multifunctional proximal colon requires specific additional circuit components as compared to the distal colon, where peristalsis is the predominant motility pattern. Our study reveals that motility control is hard-wired in the enteric neural networks and that circuit complexity matches the motor pattern portfolio of specific intestinal regions.

The large intestine from fetal period to adulthood and its impact on the course of colonoscopy.

The human large intestine in the living adult has a total length of about 1300 mm, ranging from 1100 to 2108 mm. The development of the gut continues after birth, up to the age 4-5. The large intestine ascends at the beginning in the right abdominal quadrant, then it traverses the abdominal cavity, and finally it descends to the anus. The left and right colic flexures are the basic flexions between the transverse, ascending and descending colon, respectively. Additionally, there are secondary bendings between intestinal segments. The angles between the neighbouring parts can vary between examined subjects. Most of the angulations can be found in the transverse (range 2-9) and sigmoid colon (range 1-9), making them the most troublesome parts to pass with a colonoscope. Colonoscopy (usually performed in the left lateral or supine position) is one of the most important examination of the large intestine mucus membrane. During this procedure the endoscope is passed through the colon into the cecum or terminal ilium. The individual anatomical features (tortuosity, supernumerary loops and elongation) may slow down or interfere with the progress of the scope. We summarize current knowledge on the human large intestine from the fetal period to adulthood and carve out some aspects that are currently less known to colonoscopists.

Developmental milestones in neonatal and juvenile C57Bl/6 mouse - Indications for the design of juvenile toxicity studies.

There is a growing demand for wild type mice and mouse models of disease that may be more representative of human conditions but there is little information on neonatal and juvenile mouse anatomy. This project produces sound and comprehensive histology background data on the developing neonatal mouse at different time points from Day 0 until Day 28. The work describes optimal methods for tissue harvesting, fixation and processing from the neonatal and juvenile mice which can be used in routine toxicology studies. A review of the available literature revealed inconsistencies in the developmental milestones reported in the mouse. Although it is true that the sequence of events during the development is virtually the same in mice and rats, important developmental milestones in the mouse often happen earlier than in the rat, and these species should not be used interchangeably.

Electron microscopic study of novel threadlike structures on the surfaces of mammalian organs.

The ultrastructures of novel threadlike structures (NTSs) and corpuscles on the surfaces of internal organs of rats were investigated using electron microscopy. The samples were studied in situ by using a stereomicroscope and were taken for further morphological analysis. Scanning electron microscope (SEM) images revealed a bundle structure of threadlike tissue, which was composed of several 10-micro m-thick subducts. The surfaces of the corpuscles were rather coarse and fenestrated. The corpuscles had cucumber-like shapes with an average length of about 2 mm and a thickness of about 400 micro m. Transmission electron microscope (TEM) images disclosed disordered collagen fibers, which formed the extracellular matrix of the threadlike tissue, and immune-function cells, like macrophages, mast cells, and eosinophils. Sinuses of various diameters, which were thought to be cross-sections of the lumens of the subducts, were observed in the TEM, cryo-SEM and focused-ion-beam SEM images. These SEM images were obtained for the first time to reveal the detailed structure of the NTSs that were only recently discovered.

Dose-dependent effects of T-2 toxin on performance, lipid peroxidation, and genotoxicity in broiler chickens.

The objective of the present study was to evaluate the effects of different concentrations of T-2 toxin in feed on performance, lipid peroxidation, and genotoxicity in vivo. For a 17-d period, T-2 toxin was added to the diet of the chickens. Fifty 22-d-old male broiler chickens were divided into 5 groups that were supplemented with different concentrations of T-2 toxin: control (0.0 mg/kg of feed), T 0.5 (0.5 mg/kg of feed), T 1.5 (1.5 mg/kg of feed), T 4.5 (4.5 mg/kg of feed), and T 13.5 (13.5 mg/kg of feed). Deoxyribonucleic acid fragmentation in spleen leukocytes, malondialdehyde in plasma and liver, total plasma antioxidative status, glutathione peroxidase activity, and total serum Ig (IgA and IgG) were measured. Feed consumption and BW gain decreased when the concentration of T-2 toxin was 4.5 and 13.5 mg/kg of feed. Compared with the control group, the rate of DNA damage increased significantly in the group fed 13.5 mg of T-2 toxin/kg of feed. In contrast to DNA fragmentation, indicators of oxidative stress did not show differences between groups fed T-2 toxin and the control. More serum IgA was detected in the group T 13.5 compared with the control, whereas there were no differences in serum IgG levels. The results of the present study indicate that impaired performance, DNA fragmentation in spleen leukocytes, and elevated serum IgA levels induced by T-2 toxin are dose-dependent. Based on our results, we could not confirm the hypothesis that oxidative stress is among the mechanisms by which T-2 toxin induces DNA fragmentation.

Absorción mineral y retención ósea en ratas normales en crecimiento por el consumo de un yogur experimental reducido en lactosa que contiene galactooligosacáridos (GOS) / Mineral absorption and bone retention in normal growing rats by consumption of an experimental lactose-reduced yogurt containing galactooligosaccharides (GOS)

Introducción: Los GOS son prebióticos naturales presentes en la leche materna que pue-den obtenerse enzimáticamente a partir de la lactosa de leche de vaca durante la fabricación de yogur. El producto lácteo resultante será reducido en lactosa y contendrá prebióticos y bacterias potencialmente probióticas. Sin embargo, mantendrá la baja relación Ca/Pi que aporta la leche de vaca, lo que podría alterar el remodelamiento óseo y la mineralización. Objetivo: comparar si un yogur reducido en lactosa que contiene GOS (YE) ofrece ventajas adicionales respecto de un yogur regular sin GOS (YR) sobre las absorciones (Abs) de Ca y Pi, retención y calidad ósea durante el crecimiento normal. Al destete, ratas machos fueron divididas en 3 grupos alimentados con AIN ́93-G (C), YE o YR durante 28 días. Resultados: YE mostró el mayor aumento de lactobacilos fecales; producción de ácidos grasos de cadena corta especialmente p, profundidad de las criptas colónicas y menor pH cecal. El %AbsCa y %AbsPi aumentó en el siguiente órden: YE> YR> C (p < 0,05). El contenido de Ca y Pi en fémur, la densidad y contenido mineral óseos y los parámetros biomecánicos fueron similares en YE y C, mientras que YR mostró valores significativa-mente menores (p < 0,05). Conclusiones: YE aumentó las Abs y biodisponibilidad de minerales, alcanzando la retención y calidad ósea de C. El aumento en las Abs observado en YR no logró obtener la retención y calidad ósea de C. Conclusión: YE habría contrarrestado el efecto negativo del mayor aporte de Pi de la leche de vaca y sería una buena estrategia para lograr el pico de masa ósea y calidad del hueso adecuados, especialmente en individuos intolerantes a la lactosa. (AU)

Breast milk contains an optimal calcium/phosphate (Ca/Pi) ratio and GOS. These natural prebiotics can be enzymatically produced via cow's milk lactose inyogurt manufacture. This milk product is low in lactose and contains prebiotics and potentially probiotic bacteria but maintains a low Ca/Pi ratio that could alter bone remodeling and mineralization. We evaluated if a lactose-reduced yogurt containing GOS (YE) offers additional advantages over regular yogurt without GOS (YR) on Ca and Pi absorption (Abs), bone retention and quality during normal growth. Weaning male rats were divided into 3 groups fed AIN'93-G (C), YE or YR for 28 days. Results: YE showed the highest increase in fecal lactobacilli; short-chain fatty acids production, especially propionate and butyrate; intestine crypt depth, and the lowest cecal pH. AbsCa% and AbsPi% increased in this order: YE> YR> C (p <0.05). Ca and Pi content in femur, bone density and mineral content, and biomechanical parameters were similar in YE and C, while YR showed the significantly lowest value (p < 0.05). Conclusions: YE increased mineral Abs reaching the retention and bone quality of C. Although YR increased Abs, bone retention and quality did not achieve C values. Seemingly, YE compensated for the negative effect of the higher Pi supply and would be a good strategy to achieve adequate peak bone mass and bone quality, especially in lactose intolerant individuals. (AU)

The role of polyamines in glucagon-like peptide-2 prevention of TPN-induced gut hypoplasia.

Total parenteral nutrition (TPN) of rats has been demonstrated to produce hypoplasia of gut mucosa, and to be associated with reduced immune response and elevated translocation of bacteria from gut to mesenteric lymph nodes, spleen and liver. Treatment of rats being maintained on TPN with the proglucagon fragment, glucagon-like peptide-2 (GLP-2), has been shown to totally prevent small intestine mucosal hypoplasia. In the present study, we found that depletion of polyamines with alpha-difluromethylornithine (DFMO) significantly reduced the efficacy of GLP-2 in preserving gut mucosa in rats maintained on TPN for 8 days. Co-infusion of GLP-2 with TPN prevented loss of protein and mucosa in duodenum, jejunum and ileum, but not in colon. Addition of DFMO to the infusate prevented the protective effects of GLP-2 in the duodenum and jejunum. In the jejunum, putrescine and spermidine were reduced in DFMO-treated rats, while the ileum exhibited reductions of these polyamines in rats infused with TPN or TPN plus GLP-2. DFMO infusion further reduced these polyamines in the ileum, while levels of spermine were increased. Concentrations of ornithine decarboxylase were elevated in jejunum of rats infused with TPN or TPN plus GLP-2, but were reduced significantly in DFMO-treated rats. These results suggest that normal levels of polyamines are necessary for the expression of GLP-2-induced hyperplasia. Differential effects of GLP-2 and DFMO across gut segments may relate to regional differences in proliferative and anti-apoptotic effects of the treatments.