Loss Of Interstitial Cells Research Articles

Telocytes, c-Kit positive cells, Smooth muscles, and collagen in the ureter of pediatric patients with congenital primary obstructive megaureter: elucidation of etiopathology

ABSTRACT Congenital primary obstructive megaureter (POM) is an uncommon pediatric anomaly that is due to obstructive distal ureter leading to the loss of peristalsis with consequent ureterohydronephrosis causing loss of kidney function. The objectives are to elucidate the etiology of POM by demonstrating the presence of interstitial cells of Cajal (ICC), telocytes, smooth muscles, and collage in the obstructive and dilated ureteral segments. The study was carried out on 15 surgical specimens of congenital POM in pediatric patients, age range was 4 to 24 months, they were operated upon by excision of the obstructed segment, tailoring the dilated ureter, and anastomosing it to the bladder. Specimens included the obstructed ureteral segment and part of the dilated ureter. Specimens were examined with hematoxylin and eosin (H&E) stain, Modified Gomori trichrome stain, immunohistochemistry (IHC) with α-muscle actin, and c-kit (CD117), and transmission electron microscopy (TEM). Obstructed segment showed excess collagen intervening between smooth muscles, excess c-Kit positive cells, and presence of telocytes. The dilated segment of the ureteral wall is formed of smooth muscle bundles with scanty collagen. Staining with c-Kit did not demonstrate positive cells. TEM showed myofibroblasts and close adherence of smooth muscle cells to each other with absence of telocytes. The pathophysiology of POM is multifactorial. Loss of interstitial cells and rarity of collagen result in loss of elasticity of dilated segment leading to massive dilatation. While the obstructed segment had no muscle conductivity due to excess collagen irrespective of presence of telocytes.

Functional Foods in the Therapeutic Management of Diabetic Gastroenteropathy.

Diabetic gastroenteropathy is one of the main morbidities in long-term diabetic patients, which causes several symptomatic manifestations, such as heartburn, abdominal pain, nausea, vomiting and even constipation, diarrhea and fecal incontinence. Its pathophysiology differs for each organ and may be caused by neuropathy of the autonomic nervous system, by loss of interstitial cells in Cajal, as well as by oxidative stress resulting from hyperglycemia. Its main therapeutic interventions include maintaining glycemic control. In such context, nutritional therapy based on functional foods might emerge as an alternative treatment for diabetic gastroenteropathy due to the presence of bioactive compounds that assist the glycemic control, improving the quality of life of patients. Therefore, this study aimed to investigate, in the scientific literature, functional foods that have a role in glycemic homeostasis and the diabetic complications of the gastrointestinal tract. Cinnamon, oats, guava, yacon potatoes, pumpkin, flaxseed and avocado were among the functional foods studied here.

Diabetic Gastroparesis: A Review.

Gastroparesis is characterized by delayed gastric emptying in the absence of mechanical obstruction. This complication is associated with uncontrolled diabetes, contributing to approximately one-third of all gastroparesis cases (1–3). Gastroparesis is more prevalent in patients with type 1 diabetes than in those with type 2 diabetes (4). The 10-year cumulative incidence of diabetic gastroparesis has been estimated to be 5.2% in patients with type 1 diabetes and 1% in those with type 2 diabetes (5,6). The prevalence of diabetes-associated gastrointestinal symptoms is 5–12% (7,8). In a study by Jung et al. (9) conducted in Olmsted County, MN, the prevalence of gastroparesis was about 5% in patients with type 1 diabetes and 1% in type 2 diabetes (9). In the same study, the age-adjusted incidence rate of gastroparesis was 2.4/100,000 person-years in men and 9.8/100,000 person-years in women (9). Gastroparesis, a form of autonomic neuropathy, is most commonly seen in people who have had diabetes for >10 years and who have already developed other microvascular complications (10). Once the symptoms from gastroparesis begin, they typically persist and are stable over 12–25 years; this is true even when blood glucose levels have been controlled (11). The most common symptoms are early satiety, nausea, bloating, abdominal pain, and vomiting. In terms of prognosis, a recent study published by Chang et al. (12) found no association between delayed gastric emptying and increased mortality over a 25-year period. Although there is no evidence to date that diabetic gastroparesis increases mortality, this complication substantially impairs all aspects of life (13). Although still not fully elucidated, the suggested pathophysiology of diabetic gastroparesis includes poor glycemic control, sympathetic vagal neuropathy, Cajal interstitial cell abnormalities, and loss of neuronal nitric oxide synthase (nNOS) (3,14). The loss of interstitial cells …

Tu1258 – Mast Cell Infiltration Associated with Loss of Interstitial Cells of Cajal and Neuronal Degeneration in Achalasia

Tu1258 – Mast Cell Infiltration Associated with Loss of Interstitial Cells of Cajal and Neuronal Degeneration in Achalasia

Electroacupuncture at ST36 Increases Bone Marrow-Derived Interstitial Cells of Cajal via the SDF-1/CXCR4 and mSCF/Kit-ETV1 Pathways in the Stomach of Diabetic Mice.

Background The loss of interstitial cells of Cajal (ICC) is observed in diabetic gastroparesis. Electroacupuncture (EA) maintains ICC networks, but the effects and mechanisms of EA on ICC of bone marrow derivation in the stomach have not been investigated. Methods C57BL/6 mice were randomized into six groups: control, diabetic (DM), bone marrow transplantation (BMT) + DM, BMT + DM + sham EA (SEA), BMT + DM + low-frequency EA (LEA), and BMT + DM + high-frequency (HEA). c-Kit+GFP+ cells in the stomach were detected by immunofluorescence staining. Western blotting and qRT-PCR were employed to determine c-Kit, GFP, SDF-1, CXCR4, mSCF, pERK, and ETV1 expression. Results (1) c-Kit+GFP+ cells were elevated in the BMT + DM + LEA and HEA groups. (2) The mRNA and protein levels of GFP, SDF-1, and CXCR4 were increased in the BMT + DM + LEA and BMT + DM + HEA groups. (3) The mRNA and protein levels of mSCF, c-Kit, pERK, and ETV1 were significantly reduced in the DM group but markedly elevated in the BMT + DM + LEA and HEA groups. Conclusion EA at ST36 increases bone marrow-derived ICC in the stomach of diabetic mice via the SDF-1/CXCR4 and mSCF/c-Kit-ETV1 pathways.

Decrease of Nitrergic Innervation in the Esophagus of Patients with Chagas Disease: Correlation with Loss of Interstitial Cells of Cajal

Decrease of Nitrergic Innervation in the Esophagus of Patients with Chagas Disease: Correlation with Loss of Interstitial Cells of Cajal

Interstitial cells: regulators of smooth muscle function.

Smooth muscles are complex tissues containing a variety of cells in addition to muscle cells. Interstitial cells of mesenchymal origin interact with and form electrical connectivity with smooth muscle cells in many organs, and these cells provide important regulatory functions. For example, in the gastrointestinal tract, interstitial cells of Cajal (ICC) and PDGFRα(+) cells have been described, in detail, and represent distinct classes of cells with unique ultrastructure, molecular phenotypes, and functions. Smooth muscle cells are electrically coupled to ICC and PDGFRα(+) cells, forming an integrated unit called the SIP syncytium. SIP cells express a variety of receptors and ion channels, and conductance changes in any type of SIP cell affect the excitability and responses of the syncytium. SIP cells are known to provide pacemaker activity, propagation pathways for slow waves, transduction of inputs from motor neurons, and mechanosensitivity. Loss of interstitial cells has been associated with motor disorders of the gut. Interstitial cells are also found in a variety of other smooth muscles; however, in most cases, the physiological and pathophysiological roles for these cells have not been clearly defined. This review describes structural, functional, and molecular features of interstitial cells and discusses their contributions in determining the behaviors of smooth muscle tissues.

Inflammation induced by mast cell deficiency rather than the loss of interstitial cells of Cajal causes smooth muscle dysfunction in W/Wv mice

The initial hypothesis suggested that the interstitial cells of Cajal (ICC) played an essential role in mediating enteric neuronal input to smooth muscle cells. Much information for this hypothesis came from studies in W/Wv mice lacking ICC. However, mast cells, which play critical roles in regulating inflammation in their microenvironment, are also absent in W/Wv mice. We tested the hypothesis that the depletion of mast cells in W/Wv mice generates inflammation in fundus muscularis externa (ME) that impairs smooth muscle reactivity to Ach, independent of the depletion of ICC. We performed experiments on the fundus ME from wild type (WT) and W/Wv mice before and after reconstitution of mast cells by bone marrow transplant. We found that mast cell deficiency in W/Wv mice significantly increased COX-2 and iNOS expression and decreased smooth muscle reactivity to Ach. Mast cell reconstitution or concurrent blockade of COX-2 and iNOS restored smooth muscle contractility without affecting the suppression of c-kit in W/Wv mice. The expression of nNOS and ChAT were suppressed in W/Wv mice; mast cell reconstitution did not restore them. We conclude that innate inflammation induced by mast cell deficiency in W/Wv mice impairs smooth muscle contractility independent of ICC deficiency. The impairment of smooth muscle contractility and the suppression of the enzymes regulating the synthesis of Ach and NO in W/Wv mice need to be considered in evaluating the role of ICC in regulating smooth muscle and enteric neuronal function in W/Wv mice.

S2062 Age-Related Loss of Interstitial Cells of Cajal in the Human Colon

G A A b st ra ct s value of 0.7. However, mean ICC size did not change (P=0.18). Conclusion: There is a significant decrease in ICC numbers and network volumes with age in the human gastric body. These observations also suggest that studies on gastric tissues and functions must include carefully age-matched controls. Support: BFU-2007-60563, DK57061, DK68055 and DK52766. PJGP is supported byMECYT and FUNDECYT.MJP is supported by RETICEF.

472 Decreased Mortality in Acute Pancreatitis Related to Early Aggressive Hydration

Background: Gastroparesis is a well recognized complication of diabetes and can contribute to poor glycemic control. Diabetic gastroparesis is associated with loss of interstitial cells of Cajal. We have previously studied gastroparesis by serially measuring gastric emptying in diabetic NOD mice and demonstrated that delayed gastric emptying is associated with loss of up-regulation of heme oxygenase-1 (HO1), an increase in oxidative stress and loss of Kit. Induction of HO1 reversed delayed gastric emptying, lowered markers of oxidative stress and restored Kit expression. HO1 catalyzes the breakdown of heme into iron, biliverdin and carbon monoxide (CO). The metabolite of HO1 that restores normal gastric function is not known. Aims: Determine whether inhalation of CO can reduce oxidative stress, increase Kit expression and reverse delayed gastric emptying in diabetic NODmice.Methods: Gastric emptying of solids was measured using a [13C]octanoic acid based breath test. Mice were considered diabetic when blood glucose levels were >250 mg/dL. Mice that developed delayed gastric emptying (T1/2 >118min) received either CO by inhalation (250 ppm for 6 hours daily) or not. Serum malondialdehyde was measured as a marker of oxidative stress. Kit and HO1 expression levels were determined in immunoblots of protein extracted from the external muscle layers of the body and antrum of the stomach. Statistical analyses were done using paired t test and Mann Whitney rank-sum test for non parametric data. Results: 8 NOD mice with delayed gastric emptying were studied (mean T1/2±SEM: 160±10 min, normal 67-118 min). CO treatment reversed the gastric emptying delay in all 4 mice within 2 weeks of treatment (mean T1/2±SEM: 81±5 min, n=4), whereas gastric emptying remained delayed in all the control animals (mean T1/2±SEM: 181±8 min, n = 4). In CO treated mice, malondialdehyde levels were reduced from 394±21 nmol/ml to 41±14 nmol/ml, mean±SEM, n = 3, p 0.05, Mann Whitney). Conclusions: CO decreased oxidative stress and increased Kit expression and reversed diabetic gastroparesis in NODmice without an increase in HO1 expression. These data suggest that the production of CO by HO1 is a major contributor to the protective effect of HO1 on diabetic gastroparesis in mice. Supported by NIH DK68055 and DK57061.

Loss of interstitial cells of Cajal may be central to poor intestinal motility in diabetes mellitus

Loss of interstitial cells of Cajal may be central to poor intestinal motility in diabetes mellitus

Loss of interstitial cells of Cajal and neuromuscular transmission caused by imatinib administration in gastric fundus

Loss of interstitial cells of Cajal and neuromuscular transmission caused by imatinib administration in gastric fundus

Interstitial cells of Cajal could regenerate and restore their normal distribution after disrupted by intestinal transection and anastomosis in the adult guinea pigs

Surgical manipulations of the gastrointestinal (GI) tract usually lead to loss of interstitial cells of Cajal (ICCs). The present study prepared to investigate whether ICCs can regenerate and restore their normal distribution up to 5 months after semitransection and end-to-end anastomosis of small intestines of adult guinea pigs. The segments of anastomosis were studied by immunohistochemistry with anti-KIT, 5-bromo-2'-deoxyuridine (BrdU), stem cell factor (SCF), and neurofilament 200 antibodies and also by transmission electron microscopy (TEM). At early stage, intestinal surgery led to intestinal wall impairment and ICCs loss, and ICCs near the site of anastomosis gradually increased in numbers. About 150 days postoperation, the distribution of ICCs and the microstructure of intestinal wall appeared to be similar with those of the control. By double immunostaining with BrdU and KIT antibodies, a number of proliferated ICCs were seen near the site of transection/anastomosis. Furthermore, KIT ligand, SCF, was mainly observed in the smooth muscle cells (SMCs), which are located close to ICCs. TEM observation revealed a number of immature and mature ICCs in this region. Our results indicated that ICCs could regenerate and restore their normal distribution after intestinal surgery and SMCs might be involved in the regenerated events of ICCs in the adult guinea pig GI tract.

Spontaneous papillary necrosis in the heterozygous Gunn rat

Spontaneous papillary necrosis develops in aging heterozygous non-jaundiced Gunn rats. The lesion is situated in the subapical or mid papilla and in its earliest stages is manifest by the appearance of amorphous material in the interstitial space. This is seen in plastic-embedded sections taken from rats 6 months old. In its later stages, the accumulation of amorphous material is accompanied by loss of interstitial cells and cyst formation, but there is no associated inflammatory reaction. The largest lesions are found in the oldest rats, but even in these animals the macroscopic appearance of the papilla is normal. Similar papillary changes were not found in albino or homozygous Gunn rats, but in aging albino rats there was loss of papillary interstitial cells without accumulation of amorphous material.

Reproductive toxicology of 1,3-diphenylguanidine: analysis of induced sperm abnormalities in mice and hamsters and reproductive consequences in mice.

The effects of 1,3-diphenylguanidine (DPG) on seminal cytology in hybrid mice and inbred Syrian golden hamsters and on testicular histology and reproductive toxicity in mice were monitored. Treatment consisted of chronic exposure of hamsters and mice to DPG in 0.025% acetic acid ad libitum. Sperm morphology and sperm count, testicular cytology and histology, and reproductive toxicity were monitored 1 wk after exposure. The results show that DPG induces (1) time- and dose-dependent morphologically anomalous sperm in mice and hamsters; (2) significant decreases in sperm count and testicular weight; (3) irregularly shaped seminiferous tubules characterized by the absence of a defined basement membrane, loss of interstitial cells, and limited number of spermatids and spermatozoa in the lumen of the tubules; and (4) reduced fertility indices, implants per pregnancy, and fetal mortality in mice. The coincidence of increased morphologically anomalous sperm and drastic reductions in fertility indices and implants per pregnancy is suggestive of developmental disturbances in the preleptotene and late-spermatogonial cells (5-7 wk after treatment).