Developmental changes in submucosal nitrergic neurons in the porcine distal colon.
ABSTRACT As our understanding of the enteric nervous system improves, it becomes clear that it is no longer sufficient to simply determine whether enteric ganglion cells are present but also to determine whether correct number and types of ganglion cells are present. Nitric oxide is recognized as a potent mediator of inhibitory nerves responsible for the relaxation of the smooth muscle of the gastrointestinal tract. The aim of this study was to determine the normal nitrergic neuronal density and morphology in the submucosal plexus of the porcine distal bowel from fetal life to adulthood.
Distal large bowel specimens were obtained from porcine fetuses of gestational age E60 (n = 5), E90 (n = 5), 1-day-old piglets (n = 5), 4-week-old piglets (n = 5), 12-week-old piglets (n = 5), and adult pigs (n = 5). Whole-mount preparations of the submucosal plexus were made and stained with NADPH diaphorase histochemistry. The ganglia density, the number of ganglion cells per ganglia, and nucleus and cytoplasmic area were measured.
Ganglia density decreased progressively and markedly with age until the adulthood (P < .001). On the contrary, ganglion cells increased their size over time predominantly because of increase in cytoplasm (P < .001). The number of ganglion cells per ganglia increased significantly during the fetal life. However, there was a significant reduction in the number of ganglion cells per ganglia during the period from birth to 4 weeks, remaining constant thereafter (P < .001).
The quantitative and qualitative morphometric analysis of the colonic submucous plexus shows that significant developmental changes occur during fetal and postnatal life. These findings indicate that the age of the patient is of utmost importance during histopathologic evaluation of enteric nervous system disorders.
- Journal of Pediatric Surgery 05/2002; 37(4):551-67. · 1.38 Impact Factor
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ABSTRACT: Between 1986 and 1991 773 infants were investigated by biopsy. 209 children suffered from a neuronal dysplasia of the submucous plexus (NID B). 64 of these 209 cases had concomitant Hirschsprung's disease with NID. The combination of Hirschsprung's disease with NID was established at biopsy not earlier than at 12 +/- 6 months of age. The classical form of an isolated aganglionosis had a median age at diagnosis of 4 +/- 2 months. The preconditions for a reliable diagnosis of NID are mucosal biopsies with submucosa taken 1, 3 and 9 cm above the pectinate line, the preparation of 15 microns thick serial sections, a acetylcholinesterase- and lactate-reaction and a systematic examination of all serial sections. Giant ganglia, which are 2-3 times as large as normal ganglia and having more than 7 LDH-positive nerve cells (10 +/- 3 nerve cells in the mean), are the most relevant parameters in the diagnosis of NID. They can be observed in infants as well as in adults. The NID proximal to aganglionosis is in principle not different from an isolated form of NID. Increase of acetylcholinesterase-activity in muscularis mucosae and lamina propria mucosae and a "hyperplasia" of the submucous plexus in early infancy disappears with advancing age and are very seldom observed at 2 years of age or in adulthood. NID B is the mildest form of a developmental abnormality of the autonomic nervous system, which shows in most cases a spontaneous normalization of gut motility.(ABSTRACT TRUNCATED AT 250 WORDS)European Journal of Pediatric Surgery 11/1994; 4(5):267-73. · 0.84 Impact Factor
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ABSTRACT: In addition to metabolic differences, the anatomical, physiological, and biochemical differences in the gastrointestinal (G.I.) tract of the human and common laboratory animals can cause significant variation in drug absorption from the oral route. Among the physiological factors, pH, bile, pancreatic juice, and mucus and fluid volume and content can modify dissolution rates, solubility, transit times, and membrane transport of drug molecules. The microbial content of the G.I. tract can significantly affect the reductive metabolism and enterohepatic circulation of drugs and colonic delivery of formulations. The transit time of dosage forms can be significantly different between species due to different dimensions and propulsive activities of the G.I. tract. The lipid/protein composition of the enterocyte membrane along the G.I. tract can alter binding and passive, active, and carrier-mediated transport of drugs. The location and number of Peyer's patches can also be important in the absorption of large molecules and particulate matter. While small animals, rats, mice, guinea pigs, and rabbits, are most suitable for determining the mechanism of drug absorption and bioavailability values from powder or solution formulations, larger animals, dogs, pigs, and monkeys, are used to assess absorption from formulations. The understanding of physiological, anatomical, and biochemical differences between the G.I. tracts of different animal species can lead to the selection of the correct animal model to mimic the bioavailability of compounds in the human. This article reviews the anatomical, physiological, and biochemical differences between the G.I. tracts of humans and commonly used laboratory animals.Biopharmaceutics & Drug Disposition 08/1995; 16(5):351-80. · 2.09 Impact Factor