Biomedical subjects

T Wedel

Publications and source records attributed to T Wedel.

26 records · Page 2Linked to original sources

PubMed1999

Congenital colonic hypoganglionosis in murine trisomy 16--an animal model for Down's syndrome.

Human trisomy 21 (Down's syndrome) affects the development of multiple organ systems frequently including gastrointestinal anomalies such as Hirschsprung's disease. To elucidate the underlying morphogenetical mechanisms a murine model (trisomy 16 mouse) for Down's syndrome has been established. However, previous studies on trisomy 16 (TS 16) mice have been confined to non-enteric developmental disorders. Therefore, the aim of the present study was to assess the enteric nervous system and the morphology of the terminal colon in TS 16 mice during late intrauterine development. Immunohistochemical examination (protein gene product 9.5) revealed a reduction of myenteric ganglionic size and density as well as the presence of ectopic ganglia, thus resembling typical features of colonic hypoganglionosis and myenteric heterotopia. Enzyme histochemistry for NADPH-diaphorase showed a remarkable decrease of NADPH-positive neurons in TS 16 mice, whose sparse distribution was confined to a minor portion of the oligoneuronal myenteric ganglia. Electron microscopical studies of TS 16 mice confirmed the myenteric hypoganglionosis and, additionally, demonstrated the absence of submucosal neurons. Whereas neurons of controls were characterized by arborizing neuronal processes, neurons of TS 16 mice were reduced in size and exhibited only few and shortened cytoplasmic protrusions. Additionally, prominent bundles of parallel nerve fibers passed through the intermuscular zone and lacked the arborization pattern of normal neuropil. They were not observed in controls and resembled features of extrinsic nerves. Approximately one third of TS 16 mice developed a colonic dilatation proximally to an obstructed segment characterized by a pronounced hypoganglionosis. Although TS 16 mice did not develop complete aganglionosis, the abundance of nerve fiber bundles and the colonic dilatation were consistent with the morphological characteristics of Hirschsprung's disease. The findings suggest that even a hypoganglionosis characterized by ultrastructurally altered and NADPH-diaphorase-deficient neurons may be capable of provoking a functional intestinal obstruction. Similar abnormalities of the enteric nervous system as observed in TS 16 mice may also be present in such trisomy 21 patients who suffer from chronic intestinal motility disorders which are not caused by complete aganglionosis.

Animals↗

PubMed1999

[Disorders of intestinal innervation as a possible cause for chronic constipation].

The gastrointestinal tract contains the largest amount of nerve cells apart from the central nervous system constituting together with glial cells the enteric nervous system (ENS). The morphology of the ENS is characterized by intramurally located ganglionated and non-ganglionated plexus of different structure. The diversity of neurotransmitters synthesized by the different nerve cell types as well as the complex neuronal circuits establish the basis for the mediation of a coordinated intestinal motility. Subsequently abnormalities of the ENS may cause severe constipation. The most acknowledged intestinal innervation disorder represents aganglionosis (Hirschsprung's disease) characterized by the absence of intramural nerve cells and the hypertrophy of nerve fiber bundles within the affected intestinal segment. Non-aganglionic intestinal innervation disorders include intestinal neuronal dysplasia (IND), hypoganglionosis and heterotopic ganglia. The pathogenesis of intestinal neuronal malformations is mainly attributed to development disorders of the ENS, in part caused by genetic defects. Furthermore, the ENS can sustain damage during the postnatal period by ischemic, inflammatory, autoimmunological processes or neurotoxic agents. The histopathological diagnosis of intestinal innervation disorders is achieved by enzyme- and immunohistochemical methods. The examination of the ENS can be carried out on mucosal, deep submucosal or full-thickness biopsies using serial transverse sections as well as on intestinal whole-mount preparations allowing a three-dimensional demonstration and assessment of the intramural plexus. Structural abnormalities of the myenteric and submucosal plexus and an abnormal content of neurotransmitters have been considered to be responsible for primary chronic constipation. However, until now no unified pathophysiological concept has been established due to the partly contradictory findings. Therefore, an important goal in patients with chronic constipation should be a detailed quantitative and qualitative assessment of the underlying neurohistopathology. The correlation of these data with functional parameters of intestinal motility may represent an useful tool for the differential diagnostic and therapeutic considerations.

Chronic Disease↗

PubMed1998

A scanning electron microscopy study of peritoneal stomata in different peritoneal regions.

Peritoneal stomata constitute the principal pathways for the drainage of intraperitoneal contents from the peritoneal cavity to the lymphatic system and have been claimed to be exclusively restricted to the peritoneal surface of the diaphragm. This concept has been revised by the demonstration of peritoneal stomata in the omental, mesenteric, ovaric and pelvic peritoneum. Therefore, the aim of this study was to further assess peritoneal surfaces of several other abdominal organs and of the abdominal wall with special reference to the occurrence of peritoneal stomata. The peritoneum covering the spleen, stomach, intestine, liver, diaphragm and anterior abdominal wall obtained from rats was examined by scanning electron microscopy. Whereas the splenic and hepatic peritoneal surfaces were composed of uniformly distributed cuboidal mesothelial cells, the gastric and intestinal peritoneal surfaces were arranged in parallel folds composed of prominent mesothelial cells with elongated finger-like cytoplasmic processes. In addition to diaphragmatic peritoneal stomata, mesothelial openings were also found on the peritoneal surfaces covering the anterior abdominal wall and the liver. The parietal peritoneal stomata were arranged in clusters, oval in shape and delimited by flattened mesothelial cells exposing the underlying submesothelial connective tissue. The hepatic mesothelial openings formed by deep channel-like gaps of adjacent cuboidal mesothelial cells were almost completely occluded by a dense microvillous coat. As the submesothelial connective tissue was not identifiable with certainty, the mesothelial openings were regarded as corresponding to stoma-like structures. These findings yield further evidence that peritoneal stomata are obviously not confined to the diaphragmatic area but extend to other peritoneal regions. It is therefore suggested that these extra-diaphragmatic parietal and visceral peritoneal surfaces contribute to the absorption capacity of the entire peritoneum and are subsequently involved in either therapeutic procedures or pathological processes affecting the peritoneal cavity.

Animals↗

PubMed1998

Structural differences of the enteric nervous system in the cattle forestomach revealed by whole mount immunohistochemistry.

The specific motility patterns of the forestomach of ruminants, composed of three structurally distinct compartments (rumen, reticulum, omasum), require an elaborate intramural innervation. To demonstrate the complex structure of the enteric nervous system (ENS), whole mount preparations obtained from different sites of the bovine forestomach were submitted to immunohistochemical procedures in which neuronal (protein gene product 9.5, neurofilament 200) and glial (protein S-100, glial fibrillary acid protein) markers were applied. Immunohistochemistry performed on whole mounts allowed a detailed two-dimensional assessment of the architecture of the intramural nerve networks. Generally, the myenteric and submucosal plexus layers were composed of ganglia and interconnecting nerve fiber strands, whereas the mucosal plexus consisted of an aganglionated nerve network. However, the texture of the ENS showed considerable regional differences concerning the ganglionic size, shape and density and the arrangement of nerve fiber strands. The myenteric plexus of the ruminal wall, showing a low ganglionic density and wide polygonal meshes, contrasted with the nerve network within the ruminal pillar which consisted of ropeladder-like nerve fiber strands and parallel orientated ganglia. The highest ganglionic density was observed at the reticular groove, the most prominent ganglia were found within the omasal wall. Branches of the vagal nerve frequently ramified within the myenteric plexus layers. The submucosal plexus of the rumen was divided into an external and internal layer; the reticular submucosal plexus followed the cristae and cellulae reticuli, the omasal submucosal (sublaminar) plexus showed intra- and parafascicular ganglia apart from ganglia located at the junctions of the nerve network. The mucosal plexus of the rumen consisted of thin nerve fascicles ramifying between the ruminal papillae, and reticular mucosal nerve fibers passed throughout the base of the cellulae reticuli. The highly specialised nerve network of the intralaminar omasal plexus showed radial and transverse trajectories reflecting the spatial arrangement of the intralaminar musculature. The demonstrated structural complexity of the ENS reflects the functional complexity of the ruminant forestomach and indicates the relatively high degree of autonomy in coordinating the different motility patterns required for the processing of the ingesta.

Animals↗

PubMed1998

Morphologic alterations of the enteric nervous system and deficiency of non-adrenergic non-cholinergic inhibitory innervation in neonatal necrotizing enterocolitis.

Although damage to intramural nervous tissue should be expected in neonatal necrotizing enterocolitis (NNEC), as the pathology of NNEC is defined by substantial destruction of the bowel wall, only a few studies have considered its implication. Thus, the aim of the study has been to examine morphological alterations of the enteric nervous system (ENS) in intestinal segments affected by NNEC. Immunohistochemical methods allowed the demonstration of both neuronal and glial elements and the assessment of an altered localization of non-adrenergic non-cholinergic (NANC) inhibitory mediators within the intramural plexuses. Intestinal segments from patients with NNEC (n = 8) and control subjects (n = 3) were obtained and submitted to immunohistochemical examination incubating with antibodies against protein gene product (PGP) 9.5, protein S-100, vasoactive intestinal polypeptide (VIP) and nitric oxide synthase (NOS). The most severe damage of nervous tissue was found within the plexus mucosus and plexus submucosus internus. The ganglionated plexuses showed a loss ot both glial and nerve cells with various stages of cell deterioration and the formation of central lesions within the myenteric ganglia. The observed neuropathologic changes correspond to the group of acquired segmental hypoganglionosis. Specimens from patients with NNEC were also characterized by an absence of immunoreactive VIP and NOS in the plexus submucosus and within the circular muscle layer. The deficiency in NANC inhibitory innervation may contribute to the formation of functional obstructions following acute NNEC. Furthermore, it is likely that the neuropathological lesions induced in early stages of NNEC may result in dysfunctional intestinal motility facilitating intraluminal bacterial overgrowth and translocation, and therefore, possibly promote the self-perpetuating pathophysiologic cycle culminating in progressive NNEC. As an additional finding, two patients with NNEC showed typical features of intestinal neuronal dysplasia (IND). The association of NNEC and IND is reviewed in the literature and possible causalties are discussed.

Enterocolitis, Pseudomembranous↗

PubMed1998

[Megacolon in adults--the spectrum of underlying intestinal innervation disorders].

The association of megacolon in adults and Hirschsprung's disease was reevaluated by the morphological assessment of the enteric nervous system. Whole-mount preparations of the resected colonic segments and an immunohistochemical treatment with the pan-neuronal marker protein gene product 9.5 allowed an optimal visualization of the entire intramural nervous plexus layers. The findings included different forms of intestinal neuronal malformations (hypoganglionosis, neuronal intestinal dysplasia, and heterotopic ganglia) apart from classic aganglionosis, thus indicating their etiologic relevance to the development of megacolon in adults.

Adult↗

PubMed1995

Secondary hyperparathyroidism and depression in chronic renal failure.

UNLABELLED: This study was aimed at examining the relation between secondary hyperparathyroidism (sHPT) and depressive syndromes in chronic renal failure (CRF). SAMPLE AND METHODS: 59 chronic CRF patients and 16 depressive patients without CRF were included. Parathyroid hormone (PTH), calcium and phosphate as well as psychopathology were measured. RESULTS: Depressive CRF patients with cognitive disorders show higher levels of PTH than less or not depressive subjects. With respect to the literature, our results give reason to assume that sHPT may play a pathogenetic role in those depressive syndromes which are additionally characterized by cognitive disorders.

Adult↗

PubMedDate not supplied

Alterations of the enteric nervous system in neonatal necrotizing enterocolitis revealed by whole-mount immunohistochemistry.

Pathology reports on neonatal necrotizing enterocolitis (NNEC) rarely consider its effects on the enteric nervous system (ENS). Thus, the aim of this study has been to perform a two-dimensional assessment of neuropathologic lesions within the three ganglionated plexuses of the intestinal wall by means of whole-mount immunohistochemistry. Resected segments of ileum and colon affected by acute NNEC were submitted to immunohistochemical procedures using antibodies against neuronal (protein gene product 9.5) and glial (protein S-100, glial fibrillary acidic protein) proteins. Examination of the myenteric plexus and external submucosal plexus revealed a noticeable reduction in glial cells concomitant with the gradual deterioration of nerve cells, both findings predominating in the antimesenteric intestinal circumference, where ischemic lesions tend to appear first. The most severe damage of nervous tissue was observed in the plexus submucosus internus dependent on the depth of mucosal injury. The destroyed ganglia appeared like "empty baskets" (residual tangles) and housed deteriorated nerve and glial cells. Taking the anatomy of the intestinal vascular blood supply into consideration, the characteristic topography of neuropathologic lesions gives further support to an ischemic event within the cascade of different pathogenetic factors culminating in NNEC. Moreover, the demonstrated alterations of the ENS and their potential adverse effects on intestinal motility and neuroimmunologic interactions may contribute to the complex pathogenesis of NNEC, which remains a field of further investigation.

Enteric Nervous System↗