Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.1 (NADPH-diaphorase)
 3,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hirschsprung's disease (HD) is defined as a congenital absence of ganglion cells in the distal bowel. Functionally, there is a loss of enteric neuromuscular inhibition. Inhibitory intestinal innervation includes extrinsic nonadrenergic, noncholinergic (NANC) nerves. Nitric oxide (NO) is proposed to be a NANC neurotransmitter. Sites of NO synthesis can be localized using a NO-dependent nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemical assay. We present a study of the distribution of NO neural elements in patients with HD. Routine hematoxylin-eosin (HE) histology as well as histochemical localization of NO synthase activity was carried out on fixed laminae and sectioned tissue of infant colon. NO synthase positive nerve cells and fibers were found throughout the wall of the proximal ganglionated colon. In the myenteric plexus disposition of these nerves parallels the known NANC innervation. "Aganglionic" distal colon displayed disrupted ganglia and increased nerve fibers. Selective preservation of NO synthesizing neurons was also seen. Punctate labeling of an apparent nonneuronal origin was also noted on the surface of arterioles. NO stain simplifies the pathological diagnosis of HD. The presence of NO positive nerve cells in HD suggests that aganglionosis is a misnomer. The lack of characteristic HE findings in other forms of neuronal intestinal dysplasia indicates the need for routine simple, more sensitive neural staining of colonic biopsies in selected infants with constipation.
 ...
PMID:Routine use of the nitric oxide stain in the differential diagnosis of Hirschsprung's disease. 750 2

A few reports in the literature have discussed the histologic criteria for the diagnosis of allied diseases of Hirschsprung's disease in adults, and studies report that intestinal neuronal dysplasia (IND) in adults may develop from IND in infants. The aim of this study was to examine the differences between the histological findings of IND in infants and those in adults, and to assess whether allied diseases of Hirschsprung's disease (HD) in adults should be considered as congenital or acquired diseases. For these purposes, we studied nine adult patients with severe constipation, and an adult patient with acute intestinal obstruction. We routinely examined the patients using barium enema, anorectal manometry and rectal mucosal biopsy. However, in patients suspected of allied diseases, we carried out full-thickness rectal biopsies. In seven operated cases, we also examined resected intestines. The tissue samples were examined using AChE-staining, NADPH-diaphorase staining, HE-staining, and silver impregnation. Histologically, we diagnosed two males as having HD, two males as having IND, five patients (two males and three females) as having hypoganglionosis, and one female as having a degeneration of the intramural plexus. The following conclusions were drawn: 1) Inflammations such as ulcerative colitis or ischemic colitis may cause IND TYPE B in adults whose histological findings are similar to those generally seen in infants; 2) It is suggested that IND is closely related to hypoganglionosis; 3) In hypoganglionosis, a patient with findings of elevated AChE-positive nerve fibers in the mucosa and AChE-positive nerve fibers in an arterial wall may belong to a subtype of IND; 4) Most of the allied diseases of HD in adults may occur as an acquired disease, not as a congenital disease.
 ...
PMID:Histologic criteria for the diagnosis of allied diseases of Hirschsprung's disease in adults. 1210 1

The practice of regular exercise is indicated to prevent some motility disturbances in the gastrointestinal tract, such as constipation, during aging. The motility alterations are intimately linked with its innervations. The goal of this study is to determine whether a program of exercise (running on the treadmill), during 6 months, has effects in the myenteric neurons (NADH- and NADPH-diaphorase stained neurons) in the colon of rats during aging. Male Wistar rats 6 months (adult) and 12 months (middle-aged) old were divided into 3 different groups: AS (adult sedentary), MS (middle-aged sedentary) and MT (middle-aged submitted to physical activity). The aging did not cause a decline significant (p>0.05) of the number of NADH-diaphorase stained neurons in sedentary rats (AS vs. MS group). In contrast, a decline of 31% was observed to NADPH-diaphorase stained neurons. Thus, animals that underwent physical activity (AS vs. MT group) rescued neurons from degeneration caused by aging (total number, density and profile of neurons did not change with age--NADH-diaphorase method). On the other hand, physical activity augmented the decline of NADPH-diaphorase positive neurons (total number, density and profile of neurons decreased). Collectively, the results show that exercise inhibits age-related decline of myenteric neurons however, exercise augments the decline of neurons with inhibitory activity (nitric oxide) in the colon of the rats.
 ...
PMID:Exercise reduces inhibitory neuroactivity and protects myenteric neurons from age-related neurodegeneration. 1855 92

The enteric nervous system (ENS) poses the intrinsic innervation of the gastrointestinal tract and plays a critical role for all stages of postnatal life. There is increasing scientific and clinical interest in acquired or age-related gastrointestinal dysfunctions that can be manifested in diseases such as gut constipation or fecal incontinence. In this study, we sought to analyze age-dependent changes in the gene expression profile of the human ENS, particularly in the myenteric plexus. Therefore, we used the laser microdissection technique which has been proven as a feasible tool to analyze distinct cell populations within heterogeneously composed tissues. Full biopsy gut samples were prepared from children (4-12 months), middle aged (48-58 years) and aged donors (70-95 years). Cryosections were histologically stained with H&E, the ganglia of the myenteric plexus identified and RNA isolated using laser microdissection technique. Quantitative PCR was performed for selected neural genes, neurotransmitters and receptors. Data were confirmed on protein level using NADPH-diaphorase staining and immunohistochemistry. As result, we demonstrate age-associated alterations in site-specific gene expression pattern of the ENS. Thus, in the adult and aged distal parts of the colon a marked decrease in relative gene expression of neural key genes like NGFR, RET, NOS1 and a concurrent increase of CHAT were observed. Further, we detected notable regional differences of RET, CHAT, TH, and S100B comparing gene expression in aged proximal and distal colon. Interestingly, markers indicating cellular senescence or oxidative stress (SNCA, CASP3, CAT, SOD2, and TERT) were largely unchanged within the ENS. For the first time, our study also describes the age-dependent expression pattern of all major sodium channels within the ENS. Our results are in line with previous studies showing spatio-temporal differences within the mammalian ENS.
...
PMID:Age-related gene expression analysis in enteric ganglia of human colon after laser microdissection. 2536 Jan 10