Effect of Calcium-Sensitive Receptor Agonist R568 on Gastric Motility and the Underlying Mechanism.

INTRODUCTION: Calcium-sensitive receptor (CaSR) is expressed in the enteric nervous system of gastrointestinal tract. However, its role in the regulation of gastrointestinal motility has not yet been fully elucidated. We aimed to investigate the effect of the CaSR agonist - R568 on gastric motility and its potential mechanism. METHODS: In vivo, R568 was given by gavage to explore gastric emptying with or without capsaicin which specifically blocks the function of vagal afferents; neurotransmitters synthetized in the myenteric plexus of the gastric corpus and antrum were analysed by ELISA and immunofluorescence staining; gastric muscle strips contraction recording and intracellular single unit firing recording were used to study the effect of R568 on muscle strips and myenteric interstitial cells of Cajal (ICCs) ex vitro. RESULTS: Gastric emptying was inhibited by R568 in Kunming male mice, and capsaicin weakened this effect. The expression of c-fos-positive neurons increased in the nucleus tractus solitarius when R568 was treated. R568 decreased the expression of cholinergic neurons and reduced the synthesis of acetylcholine. Conversely, R568 increased the expression of nitrogenic neurons and enhanced the synthesis of nitric oxide in the myenteric plexus. Ex vitro results showed that R568 inhibited the contraction of the gastric antral muscle strip and suppressed the spontaneous firing activity of pacemaker ICCs. CONCLUSION: Activation of the gastrointestinal CaSR inhibited gastric motility in vivo and ex vitro. Transmitting nutrient signals to the brain through the vagal afferent nerve, modulating the cholinergic and nitrergic system in the enteric nervous system, and inhibiting activity of pacemaker ICCs in the myenteric plexus are involved in the mechanism of CaSR in gastric motility suppression.

Relation between Cajal Cell Density and Radiological and Scintigraphic Outcomes in Patients with Ureteropelvic Junction Obstruction.

INTRODUCTION: In this study, we aimed to investigate the correlation between Cajal cell density and preoperative and postoperative radiological and scintigraphic parameters in ureteropelvic junction obstruction (UPJO). METHODS: The study group consisted of 41 renal units (38 consecutive patients; 13 female and 25 male) surgically treated for UPJO. UPJ specimens from patients were immuno-stained with CD117 (c-kit) antibody for interstitial Cajal cells (ICCs). The relation between Cajal cell density and preoperative and postoperative radiological and scintigraphic parameters was evaluated. RESULTS: The mean age of the patients was 8.52 ± 8.86 (0-35) years. The density of Cajal cells was defined in 2 groups for convenient analysis as 0-5 cells (low) in 19 (46.3%) patients and >5 cells (moderate-high) in 22 (53.6%). There was significant difference between the preoperative and postoperative anteroposterior diameters of the related kidneys in both Cajal groups (p = 0.001-low, p = 0.000-moderate-high) independent of Cajal cell density. Regression in hydronephrosis postoperatively was determined in both Cajal groups (77.8%-low, 64.7%-moderate-high); however, there was no difference between them (p = 0.39). Preoperative T1/2 was significantly longer in the low Cajal group (p = 0.02). Postoperative T1/2 decreased in both low (p = 0.000) and moderate-high (p = 0.001) Cajal groups, but no difference was found between them (p = 0.24). There was significant improvement in the kidney differential function after surgery in the low Cajal density group (p = 0.015) while there was no correlation between the scintigraphic success or improvement and Cajal cell density (p = 0.51). DISCUSSION/CONCLUSION: ICC deficiency/density could not be shown as a predictive factor for the determination of success rate of pyeloplasty. Despite the lack of any evidence for the degree of deficiency as an indicator for the severity of obstruction and prediction of surgical success, further studies are needed for confirmation.

The impact of acute stress disorder on gallbladder interstitial cells of Cajal.

Physical and psychological stress exerts a substantial effect on gastrointestinal motility disorders, where trauma enhances symptoms of digestive dysfunction. Interstitial cells of Cajal (ICCs) act as pacemakers for gastrointestinal motility regulation and are likely important in stress-associated gastrointestinal motility disorders. This study explored the mechanisms underlying gallbladder ICCs function under acute stress conditions using a rabbit chest puncture and cholecystectomy model. The stem cell factor (SCF)/c-kit pathway is essential for the development of ICCs, and gene expression was investigated to identify stress-induced transcriptional alterations. Immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling assays were used to determine ICCs apoptosis, whereas western blot analysis and reverse-transcription polymerase chain reaction were used to detect changes in the SCF/c-kit signaling pathway. These methods revealed a reduction in ICCs via apoptosis following stress, and ICCs increased over time after stressor removal. Therefore, this study demonstrates the impact of stress on ICCs development and survival and further confirms the link between stress and gastrointestinal motility.

Acute Cholecystitis Reduces Interstitial Cells of Cajal in Porcine Gallbladder Through Decreased mRNA Synthesis.

BACKGROUND/AIMS: Acute cholecystitis is a common gastrointestinal disorder, often characterized by acute cholecystitis with gallbladder motility disorder. Interstitial cells of Cajal (ICCs) are the pacemaker cells of gut motility in the gastrointestinal tract. Disruption of ICC function is related to motility disorders. The aim of this study was to explore the cellular and molecular mechanisms of ICCs in acute cholecystitis and after the resolution of acute inflammation. MATERIALS AND METHODS: Fifty adult guinea pigs were randomly divided into five groups: a sham-administered group (control group); two groups that were intraperitoneally administered an anti-polyclonal neutrophil (PMN) antibody 24 h before common bile duct ligation (CBDL); and two groups of guinea pigs that were subjected to CBDL without receiving the PMN antibody. Guinea pigs that underwent CBDL were held for 24 h or 48 h after surgery before being subjected to laparotomy and cholecystectomy. Immunohistochemistry, TUNEL assays, western blotting, and real-time PCR were performed to determine ICC morphology and density, to detect ICC apoptosis, and to examine stem cell factor (SCF) and c-kit protein expression and SCF and c-kit mRNA levels, respectively. RESULTS: Both hematoxylin-eosin staining and histological inflammation scores in the PMN groups were lower than those in the control groups (P < 0.01). No differences were observed in ICC morphology between groups. During acute cholecystitis, ICCs numbers were reduced. Conversely, the density of ICCs increased after inflammation was relieved (P < 0.01). In addition, SCF and c-kit protein and mRNA expression levels decreased during acute cholecystitis (P < 0.05) and increased after inflammation was relieved (P < 0.05). Furthermore, ICC apoptosis increased during acute cholecystitis and decreased after resolution of acute cholecystitis (P < 0.01). CONCLUSIONS: In acute cholecystitis, ICC injury may be related to gallbladder motility disorder.

Transplantation, gene therapy and intestinal pathology in MNGIE patients and mice.

BACKGROUND: Gastrointestinal complications are the main cause of death in patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Available treatments often restore biochemical homeostasis, but fail to cure gastrointestinal symptoms. METHODS: We evaluated the small intestine neuromuscular pathology of an untreated MNGIE patient and two recipients of hematopoietic stem cells, focusing on enteric neurons and glia. Additionally, we evaluated the intestinal neuromuscular pathology in a mouse model of MNGIE treated with hematopoietic stem cell gene therapy. Quantification of muscle wall thickness and ganglion cell density was performed blind to the genotype with ImageJ. Significance of differences between groups was determined by two-tailed Mann-Whitney U test (P < 0.05). RESULTS: Our data confirm that MNGIE presents with muscle atrophy and loss of Cajal cells and CD117/c-kit immunoreactivity in the small intestine. We also show that hematopoietic stem cell transplantation does not benefit human intestinal pathology at least on short-term. CONCLUSIONS: We suggest that hematopoietic stem cell transplantation may be insufficient to restore intestinal neuropathology, especially at later stages of MNGIE. As interstitial Cajal cells and their networks play a key role in development of gastrointestinal dysmotility, alternative therapeutic approaches taking absence of these cells into account could be required.

Lineage Tracing of FOXL1+ Cells in the Tunica Muscularis Suggests Mutual Origin for Telocytes and Smooth Muscle Cells.

We recently identified a FOXL1+ intestinal subepithelial network of telocytes (TCs) without which epithelial stem and progenitor cells cannot proliferate and support regeneration. In addition to FOXL1 lineage cell distribution along the intestinal epithelium, we also observed their presence within the muscle layers. Here, we characterized FOXL1+ lineage cells along the muscle layers of the duodenum in order to understand their progeny and relation to interstitial Cajal cells (ICCs), smooth muscle cells (SMCs) and the previously reported PDGFRa+ TCs. Using a FOXL1-Cre transgenic line in conjunction with genetic lineage labeling using the Rosa26-mTmG allele, in which Cre-marked cells produce a membrane-targeted version of green fluorescent protein (GFP), we found that within the muscle layers FOXL1 lineage GFP+ cells had two main progeny; (i) elongated multinucleated SMA+ SMCs, intermingled in parallel or perpendicular to muscle fibers. (ii) TCs displaying small cell body with multiple cell processes, expressing PDGFRa and CD34. These findings may suggest a mutual origin for TCs and SMCs.

The complex involvement of the digestive tract in human defense behavior - structural and functional arguments.

The digestive system has an innate monitoring and defense capacity, which allows the recognition and elimination of different dangerous substances. The complex analysis of the intestinal content comprises the cross-interactions between the epithelial cells, the enteroendocrine cells, the neural tissue and the cellular defense mechanisms. The enteric nervous system, also called "the enteric brain" or "the second brain" is the only neuronal network outside the central nervous system capable of autonomous reflex activity. The enteric nervous system activity is mostly independent of the central nervous system, but not in all aspects. In fact, even the enteral reflexes are a consequence of the bidirectional intestine-brain relation. The central nervous and enteric nervous systems are coupled through the sympathetic and parasympathetic branches of the autonomic nervous system. The gastrointestinal functions are regulated due to the interaction between the intrinsic neurons within the gastrointestinal wall and the extrinsic neurons outside the gastrointestinal tract. Here we provide an overview of the important role of the enteric brain in defensive behavior, as well as its structural and functional particularities that make it a special organ.

Telocytes and Lymphatics of the Human Colon.

BACKGROUND: Telocytes (TCs) are a peculiar morphological type of stromal cells. They project long and moniliform telopodes, visible on various bidimensional sections. Originally regarded as "interstitial Cajal-like cells", gastrointestinal TCs were CD34+. Further double-labelling studies found that colon TCs are negative for the expressions of the PDGFR-α and α-SMA. However, the TCs in colon were not distinguished specifically from endothelial cells (ECs), vascular or lymphatic. A combinational approach is important for accurate TC identification. Hence, we designed an immunohistochemical study of human colon to check whether ECs and CD34+ TCs express different markers. METHODS: Immunohistochemistry was performed on archived paraffin-embedded samples of human colon (nine cases) for the following markers: CD31, CD34, CD117/c-kit and D2-40 (podoplanin). RESULTS: A distinctive population of CD34+ TCs was found coating the myenteric ganglia. However, also perivascular cells and vascular ECs were CD34+. c-kit expression was equally found in interstitial Cajal cells (ICCs) and perivascular cells. The CD34 TCs did not express c-kit. As they were equally CD31- and D2-40- they were assessed as different from ECs. CONCLUSIONS: Testing specific markers of ECs, vascular and lymphatic, in the same tissues in which CD34+ TCs are found, is much more relevant than to identify TCs by transmission electron microscopy alone.

Telocyte and Cajal cell distribution in renal pelvis, ureteropelvic junction (UPJ), and proximal ureter in normal upper urinary tract and UPJ obstruction: reappraisal of the aetiology of UPJ obstruction.

BACKGROUND: Telocytes and Cajal cells have been described in human urinary tract and reproductive system in women and men. Telocytes and Cajal cells have been differentiated from other interstitial cells and were described to be an element in smooth muscle conductivity. Previous studies examined the ureteropelvic junction (UPJ) segment in patients with UPJ obstruction (UPJO) and attributed the aetiology of UPJO to the low density or absence Cajal cells and telocytes. The present work aimed at the demonstration of the presence and the density of telocytes and Cajal cells in the upper urinary tract (UUT) in cases with normal UUT and UPJO. It included UPJ segment, renal pelvis, and proximal ureter. The morphological pattern of distribution of collagen in relation to smooth muscle was investigated in normal and obstructed UUT. MATERIALS AND METHODS: The study was carried out on 12 surgical specimens, 5 of them represented the normal UUT and underwent nephrectomy for oncological reasons. Seven patients underwent dismembered pyeloplasty for UPJO. Surgical specimens included renal pelvis, UPJ segment, and proximal ureter. They were subjected to standard haematoxylin and eosin stain, Gomori's trichrome stain, immunohistochemistry with c-kit, and transmission electron microscopy. RESULTS: Telocytes and Cajal cells were demonstrated in the muscular layer of both normal UUT and UPJO with high density in the proximal ureter in normal UUT as well as in UPJO. The UPJ segment in normal UUT had moderate density of Cajal cells and telocytes while in UPJO the cells were scanty or absent. Renal pelvis in normal UUT showed excess density of cells while obstructed renal pelvis showed scanty Cajal cells and telocytes. Ultrastructural study showed the presence of Cajal cells, telocytes, stem cells, fibroblasts, smooth muscle cells, and collagen in different densities and distribution in normal and obstructed UUT. CONCLUSIONS: Examination of the UPJ segment of UPJO revealed that Cajal cells and telocytes were scanty or absent, collagen to muscle ratio was high. The low density of Cajal cells and telocytes in the renal pelvis of the obstructed UUT, compared to the normal, points out to the role of the renal pelvis in the pathogenesis of UPJO.

Therapeutic effect of protease-activated receptor 2 agonist SLIGRL-NH2 on loperamide-induced Sprague-Dawley rat constipation model and the related mechanism.

PURPOSE: To investigate the therapeutic effects of protease-activated receptor 2 (PAR-2) agonist SLIGRL-NH2 on loperamide-induced Sprague-Dawley (SD) rat constipation animal models. MATERIALS AND METHODS: Loperamide was injected subcutaneously to induce constipation twice a day for 3 days. SD rats (n = 30) were randomly divided into five groups: non-constipation group (control, n = 6), constipation group (constipation, n = 6), constipation + SLIGRL-NH2 low-dosage group (SLIGRL-NH2 low, n=6), constipation + SLIGRL-NH2 high-dosage group (SLIGRL-NH2 high, n = 6), and constipation + prucalopride (positive control, n = 6). The SLIGRL-NH2 low group and SLIGRL-NH2 high group were administered with 2.5 µmol/kg and 5 µmol/kg SLIGRL-NH2, respectively, and the prucalopride group received 2 mg/kg prucalopride. The control and constipation group received 1× PBS under the same pattern. SLIGRL-NH2 and prucalopride were orally administrated once daily for 7 days. On the final day of oral administration, food intake, water intake, the number of stool pellets, weight, and fecal water content was calculated; moreover, the colons of rats in different groups were collected and histological features were examined by hematoxylin and eosin staining; furthermore, the expression of anoctamin-1 was determined by Immunohistochemical methods, and the expressions of c-kit and PAR-2 were examined using real-time quantitative polymerase chain reaction and Western blot methods; finally, the expressions of neurotransmitter vasoactive intestinal peptide (VIP) and substance P (SP) were examined using enzyme-linked immuno-sorbent assay methods. RESULTS: The feeding and excretion behaviors, intestinal transit ratio, and the histological feature of the colon in the constipated rats were all improved by SLIGRL-NH2 treatment; moreover, SLIGRL-NH2 treatment induced significant increase in the expression of PAR-2 and also increased number of interstitial Cajal cells. Furthermore, SLIGRL-NH2 also decreased the contents of the inhibitory neurotransmitter VIP and increased the expression of the excitatory neurotransmitter SP. High dose of SLIGRL-NH2 has shown similar anti-constipation effects as prucalopride. CONCLUSION: These results suggested that SLIGRL-NH2 can enhance gastrointestinal transit and alleviate in rats with loperamide-induced constipation.

Ultrastructural characteristics of myenteric plexus in patients with colorectal cancer.

INTRODUCTION: It have been found previously that colorectal cancer (CRC) is accompanied by atrophy of myenteric plexuses (MPs) localized close to the tumor. The aim of the study was to compare ultrastructure of MPs localized in the unchanged part of the colon wall distant to CRC tumor with the ultrastructure of MPs in the vicinity of CRC tumor. MATERIAL AND METHODS: The present study was conducted using post-operative material derived from 11 patients with CRC. Samples of colon wall were taken from the margin of cancer invasion and from a macroscopically unchanged segment of the large intestine, immediately fixed and processed according to the standard protocol for transmission electron microscopy studies. RESULTS: In the MPs localized in the control part of colon wall the presence of numerous unmyelinated axons and cell bodies of neurons, interstitial cells of Cajal and enteroglial cells were observed. As compared to control samples, in the MPs located close to the tumor invasion, expansion of the extracellular matrix and myelin-like structures accompanying some nerve fibers were found. The appearance of mast and plasma cells was observed within MPs in the vicinity of CRC tumor. Sporadically, apoptotic cells were present inside the MPs. CONCLUSIONS: The presence of myelin-like structures and apoptotic cells within MPs located close to tumor invasion suggests that atrophy of MPs may be caused by factors released from CRC tumor.

Intraoperative inspection of the ureteropelvic junction during pyeloplasty is not sufficient to distinguish between extrinsic and intrinsic causes of obstruction: Correlation with histological analysis.

INTRODUCTION: Based on current knowledge, it is possible to have an initial diagnosis of intrinsic or extrinsic ureteropelvic junction obstruction (UPJO) based solely on clinical and imaging findings. However, it may not be possible to strictly discriminate an intrinsic case with an additional extrinsic component from a primarily intrinsic stenosis because of lower pole aberrant vessels. These two disorders may coexist or trigger each other. Herein, we aimed to compare the histological changes observed in intrinsic and extrinsic types of UPJO. Our hypothesis is that inspecting the UPJ during pyeloplasty may not be a sufficient way to delineate the underlying cause of obstruction in every individual. MATERIAL AND METHODS: We retrospectively reviewed the data of 56 patients who had dismembered pyeloplasty. The intrinsic and extrinsic groups consisted of 38 and 18 patients, respectively. Masson's trichrome stain, CD117, and connexin 43 (Cx43) antibody were used in histopathology and immunochemistry. Statistical calculations were done with chi-square and Mann-Whitney U tests. DISCUSSION: Connexin 43 staining pattern, CD117 positive cell count, and the extent of fibrosis did not differ significantly between extrinsic and intrinsic cases. However, the difference with regard to the degree of muscular hypertrophy was close to statistical significance. The exact pathophysiological mechanism underlying UPJO has yet to be elucidated. A study directly comparing both groups histologically is indeed rare. Our study showed that there are no significant differences between the intrinsic and extrinsic groups in terms of the pacemaker activity, gap junctional communication, and extent of fibrosis. Muscular hypertrophy, which was marginally higher in our extrinsic group, may persist despite successful relocation of the obstructing vessel. The main drawbacks of our study are; the absence of a control group and the retrospective study design with its inherent selection biases. CONCLUSIONS: Immunohistochemical profiles of intrinsic and extrinsic UPJOs resemble each other. Intraoperative inspection of the UPJ may not be enough for accurate discrimination for a surgical procedure that can correct only the extrinsic cause.

Interstitial cells of Cajal are decreased in patients with gastroschisis associated intestinal dysmotility.

BACKGROUND: Gastroschisis associated intestinal dysmotility (GAID) is poorly understood. Animal experiments suggest that interstitial cells of Cajal (ICC), play an important role. METHODS: Infants with gastroschisis (GS) and GAID (time to full feed >42days) were selected. Age matched GS and control (NEC, ileal atresia, malrotation, and volvulus) samples from primary (T1) and secondary (T2) time points underwent standard histopathology and immunohistochemistry for identification of ICC, followed by evaluation of ICC numbers, distribution, morphology, relation to ganglion cells, and myenteric plexus architecture. Groups were compared using parametric and nonparametric tests. MAIN RESULTS: Twelve patients had samples available for histopathological evaluation. GAID patients had a significantly lower total number of ICCs than controls (3 vs. 8, P<0.0029). ICC number at T1 was 2.5 vs. 6 (P=0.0629) and significantly lower at T2. (3.5 vs. 11, P=0.0124). GAID patients did not show a significant increase of ICC from T1 to T2. Controls showed a significant increase of ICC over time (6 vs. 11, P=0.0408). CONCLUSION: Intestinal samples from infants with GAID who underwent stoma formation demonstrated fewer ICC than controls. There was no improvement or cell recovery during the study period. The ability to modulate ICC may have significant implications for the management of GAID.

Evaluation of the relation between interstitial cells of cajal (CD117) and serotonin receptor (5HT-3A) with postfundoplication dysphagia.

OBJECTIVE: The aim of the present study is to investigate the effect of Nissen fundoplication to the pacemaker cells of an intestinal system and the serotonin receptors on an ICC membrane. METHODS: Sixteen adult male rats were taken into study. Rats were divided in to the following two groups. Nissen fundoplication was performed to study group (Group 1) and no surgical procedures were applied to control group (group 2). The rats who were subjected to surgery and the rats without surgery were sacrificed on to postoperative 14 days. Specimens for the pathologic analysis were obtained from upper esophagus (group A) and esophagogastric junction (EGJ) (group B). Distribution of ICC and 5HT-3A were evaluated separately. RESULTS: There was a significant difference (p=0.01, p=0.02, respectively) regarding number of cells stained with CD117 between the group 1B-2B and group 2A-2B. Also there was a significant difference between (p=0.01, p=0.01 respectively) number of cells stained with 5HT-3A in groups 1A-1B and 2A-2B. However, no correlation was detected between group 1B-2B for 5HT-3A. CONCLUSION: A reduction in the number of ICC was observed in esophagogastric junctions of the fundoplication group but 5HT-3A distribution did not show a significant difference. A decrease in the number of ICC may be effective at postfundoplication dysphagia.

Superficial leiomyomas of the gastrointestinal tract with interstitial cells of Cajal.

OBJECTIVE: Some authors suggest common origin of gastrointestinal stromal tumors from stem cells, which may show diverse differentiation. There are reports in which cells morphologically identical to the interstitial cells of Cajal are found in deep leiomyomas. The aim of this study was to demonstrate CD117 positive cells in superficial gastrointestinal (GI) leiomyomas and to find other cells that would suggest diverse differentiation in histologically typical leiomyoma. MATERIALS AND METHODS: We analyzed 8 cases of superficial leiomyomas and one deep leiomyoma, received in our institutions as endoscopically or surgically obtained material. The tumor sections were immunohistochemicaly stained with CD117, CD34, NF, S100, αSMA, desmin, caldesmon and mast cell antigen. RESULTS: All leiomyomas showed diffuse positivity for αSMA, caldesmon and desmin. All of them had CD117 and CD34 positive cells morphologically identical to the interstitial cells of Cajal between smooth muscle fibers, 5 had S-100 and NF positive cells and 2 showed positivity for GFAP. The cells were found in different quantity; they were usually diffusely scattered through the tumors without predilection site, forming small groups in some areas. CONCLUSION: CD177, CD34, S-100 and NF positive cells are present in superficial leiomyomas and they may suggest common origin of GI stromal tumors.

Slow transit constipation and lower urinary tract dysfunction.

INTRODUCTION: Many theories have been proposed for the coexistence of constipation and lower urinary tract dysfunction (LUTD), such as bladder compression from a distended rectum and stimulation of sacral reflexes from a full rectum. In these cases, successful treatment of constipation should result in resolution of bladder symptoms. Some children have refractory constipation and others respond well to treatment, but once treatment is discontinued most children relapse back into their constipation. This may indicate the existence of a defect in colon motility, with a persistent peristalsis problem. The existence of a common neuromuscular disorder should be the base for both bladder and bowel dysfunction (BBD). OBJECTIVE: To study colonic transit time (CTT) in children and adolescents with refractory constipation and lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: A total of 15 children (mean age 9.7 years) with refractory constipation and LUTS were evaluated with: standardized medical history; physical examination; bladder and bowel diaries; Bristol stool scale; Rome III criteria; Dysfunctional Voiding Scoring System (DVSS); ultrasound examination of the kidneys and urinary tract, and measurement of rectal diameter; urodynamic evaluation; and a CTT study using radiopaque markers. RESULTS: Urodynamic features were abnormal in 13 out of 15 children: 10 (66.7%) presented with detrusor overactivity (DO) and voiding dysfunction (VD), two (16.7%) had isolated DO, and one (8.3%) had a VD. The CTT study was abnormal in 12 out of 15 children: nine (60%) presented with slow transit constipation, three (20%) had outlet obstruction, and three (20%) had a normal CTT study. When comparing CTT and LUTD, nine (100%) children with slow transit constipation (STC) and three (50%) with no STC had DO (P = 0.04). Seven (77.8%) children with STC and three (50%) with no STC had VD (P = 0.29). The DVSS scores ranged from 6 to 21. The subgroup with STC had a DVSS score that was significantly higher than that of the subgroup with noF STC (Figure). DISCUSSION: The present study showed a high prevalence of STC in children and adolescents with refractory constipation and LUTS. This was in accordance with previous studies that have demonstrated a rate of 50-60% of STC in children with refractory constipation. In addition, DO was found to be associated with STC, which raises the chance for the existence of a common neuromuscular disorder to be the base for both bladder and bowel dysmotility. The limitation of this study was the number of participants. CONCLUSIONS: The present study demonstrated an association between DO and STC.

Cajal-like interstitial cells as a novel target in detrusor overactivity treatment: true or myth?

INTRODUCTION: The Cajal-like intestitial cells (ICCs) act as a pacemaker and are responsible for generating smooth muscle activity in the gastrointestinal tract (GI). Interstitial cells that resemble ICCs in the GI have been identified in the urinary bladder. MATERIALS AND METHODS: This review is based on a systemic literature research. The medline/pubmed, scopus, embase, and Web of Science databases were browsed in order to identify original and review articles, as well as editorials relating to cajal-like cells, urinary bladder, detrusor overactivity, overactive bladder, glivec, etc. The controlled vocabulary of the Medical Subject Headings (MeSH) database was used to ensure the sensitivity of the searches. 40 papers met the criteria and were used for this review. RESULTS: Cajal cells lie in close proximity to the muscle cells, autonomic nerve endings, and urothelial cells. There is increasing evidence that ICCs play role in urinary tract dysfunction development (e.g. detrusor overactivity, primary obstructive megaureter, congenital ureteropelvic junction obstruction, etc.). ICCs may be responsible for generating electrical potentials and induction of detrusor muscle contractions. Novel pathomechanisms of detrusor overactivity development have been postulated, as follows: 1) the disturbance of spontaneous contractility caused by altered signal transduction of ICCs between nerves and detrusor muscle cells, and 2). the alteration in signal transduction between urothelium and afferent nerve endings via suburothelial ICCs. The c-kit receptor is not only a detection marker of these cells, but may also play a crucial role in the control of bladder function. CONCLUSIONS: Cajal cells in urinary bladder suggest that the c-kit receptor may provide a novel target for treating detrusor overactivity. The review presents the current knowledge of ICCs, its role in urinary bladder function, and potential novel therapeutic strategy.

Presence of c-kit positive cells in fetal and adult bovine forestomachs.

The interstitial cells of Cajal (ICC) have been reported to regulate gastrointestinal motility. We investigated the distribution and the morphological and morphometric characteristics of the immunohistochemical reaction against c-kit in the forestomachs of fetal, newborn and adult cows. The anti-c-kit reaction revealed different populations of ICC among age groups and organs. ICC were more numerous and smaller in fetuses. Larger ICC were identified in newborns, except for those in the rumen. During the earliest stages of development, ICC were abundant in the inner layer of the muscularis and were consistently associated with this layer. In all samples, ICC were found in the outer layer of the tunica muscularis. ICC were found between the two muscle layers in the omasum at all ages; however, they were identified only in the rumen of the adult. Our study demonstrated that ICC are present in the forestomach of bovines.

Network of telocytes in the temporomandibular joint disc of rats.

The phenotypes of the temporomandibular joint (TMJ) disc cells range from fibroblasts to chondrocytes. There are relatively few reported studies using transmission electron microscopy (TEM) to determine the ultrastructural features of these cells. It was hypothesized that at least a subpopulation of TMJ stromal cells could be represented by the telocytes, cells with telopodes. In this regard a TEM study was performed on rat TMJ samples. Collagen-embedded networks were found built-up by cells with telopodes with subplasmalemmal caveolae, moderate content in matrix secretory organelles and well-represented intermediate filaments. Appositions of cell bodies were found. Prolongations of such cells were closely related to nerves and microvessels. Our study indicates that the TMJ disc attachment seems equipped with telocytes capable of stromal signaling. However, further studies are needed to assess whether the telocytes belong to a renewed cell population derived from circulating precursors.

Spontaneous Perforation as a First Presentation of Ileal Gastrointestinal Stromal Tumour (GIST) with Synchronous Breast Sarcoma.

Gastrointestinal Stromal Tumours (GIST's) are the most common mesenchymal neoplasms of the gastrointestinal tract. Majority of the GISTs are asymptomatic and often diagnosis is incidental. Synchronous second malignancies have been reported in patients with GIST. We report a case of 50-year-old female presenting with features of hollow viscous perforation, found to have ileal GIST with perforations along with a synchronous breast sarcoma. GIST with spontaneous perforation as its first clinical manifestation is rare. Synchronous occurrence of an ileal GIST with a breast sarcoma is unique and deserves reporting. This case report highlights the varied nature of clinical presentation of the GIST and also stresses on the importance of extensive search for the synchronous second malignancies in the extra abdominal sites as well.