Urocortin 2 treatment is protective in excitotoxic retinal degeneration.

Urocortin 2 (Ucn 2) is a corticotrop releasing factor paralog peptide with many physiological functions and it has widespread distribution. There are some data on the cytoprotective effects of Ucn 2, but less is known about its neuro- and retinoprotective actions. We have previously shown that Ucn 2 is protective in ischemia-induced retinal degeneration. The aim of the present study was to examine the protective potential of Ucn 2 in monosodium-glutamate (MSG)-induced retinal degeneration by routine histology and to investigate cell-type specific effects by immunohistochemistry. Rat pups received MSG applied on postnatal days 1, 5 and 9 and Ucn 2 was injected intravitreally into one eye. Retinas were processed for histology and immunocytochemistry after 3 weeks. Immunolabeling was determined for glial fibrillary acidic protein, vesicular glutamate transporter 1, protein kinase Cα, calbindin, parvalbumin and calretinin. Retinal tissue from animals treated with MSG showed severe degeneration compared to normal retinas, but intravitreal Ucn 2 treatment resulted in a retained retinal structure both at histological and neurochemical levels: distinct inner retinal layers and rescued inner retinal cells (different types of amacrine and rod bipolar cells) could be observed. These findings support the neuroprotective function of Ucn 2 in MSG-induced retinal degeneration.

Effect of particle size on the surface properties and morphology of ground flax.

Flax fibers were ground with a ball-mill and four fractions with different size ranges were collected by sieving. These were tested for water sorption, degree of polymerization (DP), copper number, hydroxyl number and analyzed by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and inverse gas chromatography (IGC). Significant differences were found between the properties of the flax fiber and those of the ground versions, including fragmentation of fibers, increase of water sorption, copper number, hydroxyl number and surface O/C ratio, and decrease of DP, crystallite size and dispersive component of surface energy (γs(d)). Some parameters depended on the particle size: O/C ratio and hydroxyl number had local maxima at 315-630 µm, while γs(d) increased steadily with the decrease of particle size. These relationships were explained by fiber disintegration, destruction of waxy surface layer, exposure of cellulosic components, increase of surface area and crystalline imperfections.

Systemic urocortin 2, but not urocortin 1 or stressin 1-A, suppresses feeding via CRF2 receptors without malaise and stress.

BACKGROUND AND PURPOSE: Infusion of corticotropin-releasing factor (CRF)/urocortin (Ucn) family peptides suppresses feeding in mice. We examined whether rats show peripheral CRF/Ucn-induced anorexia and determined its behavioural and pharmacological bases. EXPERIMENTAL APPROACH: Male Wistar rats (n= 5-12 per group) were administered (i.p.) CRF receptor agonists with different subtype affinities. Food intake, formation of conditioned taste aversion and corticosterone levels were assessed. In addition, Ucn 1- and Ucn 2-induced anorexia was studied in fasted CRF(2) knockout (n= 11) and wild-type (n= 13) mice. KEY RESULTS: Ucn 1, non-selective CRF receptor agonist, reduced food intake most potently (~0.32 nmol·kg(-1) ) and efficaciously (up to 70% reduction) in fasted and fed rats. The peptides' rank-order of anorexic potency was Ucn 1 ≥ Ucn 2 > >stressin(1) -A > Ucn 3, and efficacy, Ucn 1 > stressin(1) -A > Ucn 2 = Ucn 3. Ucn 1 reduced meal frequency and size, facilitated feeding bout termination and slowed eating rate. Stressin(1) -A (CRF(1) agonist) reduced meal size; Ucn 2 (CRF(2) agonist) reduced meal frequency. Stressin(1) -A and Ucn 1, but not Ucn 2, produced a conditioned taste aversion, reduced feeding efficiency and weight regain and elicited diarrhoea. Ucn 1, but not Ucn 2, also increased corticosterone levels. Ucn 1 and Ucn 2 reduced feeding in wild-type, but not CRF(2) knockout, mice. CONCLUSIONS AND IMPLICATIONS: CRF(1) agonists, Ucn 1 and stressin(1) -A, reduced feeding and induced interoceptive stress, whereas Ucn 2 potently suppressed feeding via a CRF(2) -dependent mechanism without eliciting malaise. Consistent with their pharmacological differences, peripheral urocortins have diverse effects on appetite.

Chronic alcohol consumption induces an overproduction of NO by nNOS- and iNOS-expressing myenteric neurons in the murine small intestine.

BACKGROUND: There are indications that alterations in the nitric oxide (NO) system of relaxation mediate gastrointestinal motor disturbances induced by chronic alcohol consumption (CAC). As CAC is known to inhibit the motility of the mouse small intestine, we investigated in this model if CAC affects basal NO synthesis by myenteric neurons and which NOS isoforms are involved. METHODS: The instantaneous NO synthesis of individual neurons was optically measured in whole-mount preparations loaded with the NO synthesis indicator DAF-FM, and the expression of nNOS, iNOS and eNOS was determined by immunohistochemistry. KEY RESULTS: The DAF-FM recordings showed that CAC induced an increase in neuronal NO synthesis (absolute fluorescence: control 34±12; CAC 140±56; mean±SD; P<0.0004). Neurons of control mice expressed the nNOS (29±3% of total) and iNOS (28±1%) isoforms. eNOS expression was observed in <0.5% of the neurons. Chronic alcohol consumption caused an increase in the proportion of iNOS-expressing neurons (to 33±5%; P<0.01) and a decrease in nNOS-expressing neurons (to 22±3%; P<0.0001), without altering the proportion of NO-producing neurons (control 55±13%; CAC 56± 11%; P=0.82). CONCLUSIONS & INFERENCES: Chronic alcohol consumption induces a marked increase in NO synthesis by jejunal myenteric neurons, accompanied by an up-regulation of iNOS-expressing neurons and a downregulation of nNOS neurons. We conclude that the overproduction of NO may be a direct cause of gastrointestinal motility disturbances.

Structural differences in the umbilical vein wall after full-term and pre-term delivery.

With the exception of its most proximal segment, the human umbilical cord lacks innervation. It might be expected, therefore, that a paracrine effect through the direct contact between the smooth muscle cells and the endothelium may be particularly important in the control of the fetoplacental circulation. In this study, electron microscopy and immunohistochemistry were applied to examine umbilical veins immediately after full-term and pre-term delivery. The smooth muscle cells in the upper layer of the tunica media exhibited long, foot-like processes with c-kit immunoreactivity. In the umbilical vein of full-term neonates more than 50% of these cell processes display a normal ultrastructure and they were closely associated with the lamina elastica interna. Whereas in pre-term infants more than 60% of these cell processes exhibit signs of severe shrinkage and detachedness from the lamina elastica interna. At the same time, the high level of immunoreactivity of the endothelial cells as regards the proapoptotic gene product Bax in pre-term infants is indicative of an enhanced apoptotic process in these cells.

Social defeat stress activates medial amygdala cells that express type 2 corticotropin-releasing factor receptor mRNA.

Defeat is a social stressor involving subordination by a threatening conspecific. Type 2 corticotropin-releasing factor receptors (CRF(2)) are abundant in brain regions implicated in defeat responses and are putative stress-related molecules. The present study sought to determine whether neuroactivation and CRF(2) expression co-occurred at brain region or cellular levels following acute defeat. Male "intruder" Wistar rats were placed into the cage of an aggressive "resident" Long-Evans rat (n=6). Upon defeat, intruders (n=6) were placed in a wire-mesh chamber and were returned to the resident's cage for an additional 75 min. Controls (n=6) were handled and returned to their home cage for the same duration. Coronal brain sections were stained for an immediate early gene product, Fos, as a neuronal activation marker. Combined immunohistochemistry with in situ hybridization was performed on a subset of brain sections from defeated intruders to visualize Fos immunoreactivity and CRF(2) mRNA jointly. Defeated rats had fivefold, sevenfold, and 10-fold more Fos-positive cells than controls in the arcuate, ventromedial nucleus of the hypothalamus, and medial amygdala post-defeat. Significant colocalization of CRF(2) mRNA and Fos-positive cells was observed in the posterior medial amygdala but not in the arcuate nucleus or ventromedial hypothalamus. The results indicate CRF(2) receptor-positive neurons in the posterior medial amygdala are involved in the neural response to social defeat.

Developmental pattern of three vesicular glutamate transporters in the myenteric plexus of the human fetal small intestine.

Three vesicular glutamate transporters (VGLUT1-3) have previously been identified in the central nervous system, where they define the glutamatergic phenotype, and their expression is tightly regulated during brain development. In the present study we applied immunocytochemistry to examine the distribution of the immunoreactivity of all three VGLUTs during prenatal development of the myenteric plexus in the human small intestine. We also investigated changes in their localization in the different segments of the small intestine and in the different compartments of the developing myenteric ganglia. Immunoreactivity against all three VGLUTs was found predominantly in the ganglionic neuropil, interganglionic varicose fibers and perisomatic puncta, but cytoplasmic labeling with different intensities also occurred. Each transporter displayed a characteristic spatiotemporal expression pattern, with the transient increase or decrease of immunoreactive cell bodies, varicosities or perisomatic puncta, depending on the fetal age, the gut segment or the ganglionic compartment. Throughout gestational weeks 14-23, VGLUT1 immunoreactivity always predominated over VGLUT2 immunoreactivity, though both peaked around week 20. VGLUT3 immunoreactivity was less abundant in the developing myenteric plexus than those of VGLUT1 and VGLUT2 immunoreactivity. It was mainly expressed in the ganglionic neuropil and in the perisomatic puncta throughout the examined gestational period. Neuronal perikarya immunoreactive for VGLUT3 were restricted to between weeks 18 and 20 of gestation and exclusively to the oral part of the small intestine.

Application of compact electron cyclotron resonance ion source.

The compact electron cyclotron resonance (ECR) ion source with a permanent magnet configuration (Kei2 source) has been developed at National Institute of Radiological Sciences for a new carbon therapy facility. The Kei2 source was designed for production of C(4+) ions; its performance such as beam intensity and stability has already reached the medical requirements. Therefore, the prototype development of the source for medical use is essentially finished. Recently, we have started a few studies on other applications of the source. One is the production of fullerenes in the ECR plasma and modified fullerenes with various atoms for new materials. A second application is the production of multiply charged ions (not only carbon) for ion implantation. In this paper, some basic experiments for these applications are reported.

Subtype-selective corticotropin-releasing factor receptor agonists exert contrasting, but not opposite, effects on anxiety-related behavior in rats.

The corticotropin-releasing factor (CRF) system mediates stress responses. Extrahypothalamic CRF1 receptor activation has anxiogenic-like properties, but anxiety-related functions of CRF2 receptors remain unclear. The present study determined the effects of intracerebroventricular administration of a CRF2 agonist, urocortin 3, on behavior of male Wistar rats in the shock-probe, social interaction, and defensive withdrawal tests of anxiety-like behavior. Equimolar doses of stressin1-A, a novel CRF1 agonist, were administered to separate rats. The effects of pyrazolo[1,5-a]-1,3,5-triazin-4-amine,8-[4-(bromo)-2-chlorophenyl]-N, N-bis(2-methoxyethyl)-2,7-dimethyl-(9Cl) (MJL-1-109-2), a CRF1 antagonist, on behavior in the shock-probe test also were studied. Stressin1-A increased anxiety-like behavior in the social interaction and shock-probe tests. Stressin1-A elicited behavioral activation and defensive burying at lower doses (0.04 nmol), but it increased freezing, grooming, and mounting at 25-fold higher (1-nmol) doses. Conversely, systemic administration of MJL-1-109-2 (10 mg/kg) had anxiolytic-like effects in the shock-probe test. Unlike stressin1-A or MJL-1-109-2, i.c.v. urocortin 3 infusion did not alter anxiety-like behavior in the shock-probe test across a range of doses that reduced locomotion and rearing and increased grooming. Urocortin 3 also did not decrease social interaction, but it decreased anxiety-like behavior in the defensive withdrawal test at a 2-nmol dose. Thus, i.c.v. administration of CRF1 and CRF2 agonists produced differential, but not opposite, effects on anxiety-like behavior. Urocortin 3 (i.c.v.) did not consistently decrease or increase anxiety-like behavior, the latter unlike effects seen previously after local microinjection of CRF2 agonists into the septum or raphe. With increasing CRF1 activation, however, the behavioral expression of anxiety qualitatively changes from "coping" to "noncoping" and offensive, agonistic behaviors.

Gastrointestinal phenotype of GAD67lacZ transgenic mice with early postnatal lethality.

It has been proposed that gamma-aminobutyric acid (GABA) in the gut may function as a neurotransmitter, hormone and/or paracrine agent. Our aim was to examine transgenic mice of the GAD67-lacZ line with impaired postnatal growth and early postnatal lethality for gastrointestinal abnormalities. The gastrointestinal tract was dissected and processed for histology, immunohistochemistry, electron microscopy, western blotting and measurement of GAD activity. Homozygous mice of both sexes displayed an intestinal phenotype characterized by a fragile and haemorrhagic intestinal wall, a reduced number of villi, epithelial lesions and the occasional appearance of pseudostratified epithelium. The number of GABA-immunoreactive enteroendocrine cells and mucin-secreting goblet cells increased significantly relative to wild-type epithelium. The appearance of GABA-immunopositive neuronal perikarya and the lack of GABA-immunoreactive varicose fibres were observed in the enteric plexuses of transgenic mice. Tissue homogenates of transgenic mice showed higher levels of expression of GAD67 and GAD65 as compared with wild-type mice. Our results suggest that the possible reason underlying the growth impairment and postnatal lethality observed in GAD67 transgenic mice is a functional impairment of GABAergic enteric neurons and disintegration of intestinal epithelium.

Spatial pattern analysis of nitrergic neurons in the developing myenteric plexus of the human fetal intestine.

BACKGROUND: Enteric nervous system precursors derived from the neural crest migrate along defined pathways to colonize the bowel. The individual cells in different environments experience different growth, differentiation, and survival conditions. Hence, the spatial distribution of the neurons is determinant with regard to functional maturation. The question arises as to whether the distribution is random or nonrandom. METHODS: Nitrergic cells were visualized by means of nicotinamide adenine dinucleotide phosphate diaphorase histochemistry. Stained specimens were photographed, and the borders of the myenteric plexus and the nuclei of the nitrergic neurons were digitalized. Plexus Pattern Analysis software was used to count the nuclei of nitrergic neurons, calculate the proportions of the areas covered by the plexus and the gut wall, and perform randomization analyses. RESULTS: The distribution pattern of the nitrergic neurons changed markedly between weeks 14 and 22 of gestation. The nitrergic neurons were randomly distributed at week 14 but were aggregated in the plexus and within the individual ganglia at week 19. The dynamics of these changes exhibited regional differences. CONCLUSIONS: The results suggest that, in addition to the gut wall and the plexus, other intraganglionic constituents may contribute to the aggregation of nitrergic cells and such examinations should be extended to other cell types in the future.

Glutathione metabolism of Acremonium chrysogenum in relation to cephalosporin C production: is gamma-glutamyltransferase in the center?

Methionine increased the intracellular glutathione (reduced) (GSH) pool and the specific gamma-glutamyltransferase (gamma-GT) activity in the cephalosporin C (CPC) producer Acremonium chrysogenum. The accelerated turnover of GSH might be indicative of the existence of a functioning gamma-glutamate cycle, and might supply the CPC biosynthetic machinery with L-cysteine. The gamma-GT was not subject to nitrogen metabolic repression but was more active in cells exposed to different oxidative-stress-generating agents. Exogenous cysteine hindered both the uptake of methionine and the induction of gamma-GT, and was not beneficial for CPC production. There was no causal relationship between the redox status of the cells and the observed cell morphology.

Computer-aided morphometric analysis of the developing concentric structure of the human fetal intestinal tube.

The Image-Pro Plus 3.0 morphometric program was used to study the region-specific organization of the human fetal intestine across the radial axis of the gut at weeks 12 and 18 of gestation. The thicknesses of the epithelium, the submucosa, the muscular layers and the myenteric ganglia were measured in resin-embedded semithin sections. Statistical analysis of the collected data was performed by using the two-way ANOVA, the SNK test and the Pearson correlation. The structural changes relating to the gut morphogenesis within this developmental period were followed both light and electron microscopically. The various tissues forming the radial axis of the intestinal tube exhibited different trends concerning their individual development. The thickness of the epithelium did not change in the fetal period investigated, although the epithelial surface displayed characteristic ultrastructural changes. The thickness of the submucosal layer increased significantly, but with different dynamics along the longitudinal axis, whereas the increases in size of the muscular layers and the myenteric ganglia did not differ significantly along the longitudinal axis of the embryonic intestine. The Pearson correlation revealed a significant correlation between the development of the circular muscle layer and that of the myenteric plexus along the whole length of the intestinal tube. The epithelium, the submucosa and the longitudinal muscle layers developed independently between weeks 12 and 18 of gestation.

Evaluation of the total number of myenteric neurons in the developing chicken gut using cuprolinic blue histochemical staining and neurofilament immunocytochemistry.

The aim of this study was to find an improved method with which to stain the entire population of myenteric neurons in the different segments of the developing chicken intestine. Histochemical staining with cuprolinic blue (quinolinic phthalocyanine) and immunostaining against neurofilament (NF) were performed on whole mounts prepared from intestinal segments of embryonic (day 19 of incubation) and hatched (1, 2, 4 and 7 days after hatching) chickens. Double labelling was performed to evaluate to what extent the two markers visualise the same nerve cell population. Cuprolinic blue stained neuronal somata highly selectively, whereas processes and glia cells were poorly labelled. The cuprolinic blue-positive neurons were uniform in shape. NF immunostaining revealed a morphologically highly variable neuron population. Double labelling with cuprolinic blue and NF resulted in an intensification of both stainings, allowing an accurate morphological classification of NF-stained myenteric neurons. Data obtained from the counting of cuprolinic blue-positive neurons were subjected to two-way ANOVA and the Tukey probe. The densities of ganglia and neurons were found to decrease, and the mean number of neurons per myenteric ganglion to increase, with different dynamics along the longitudinal axis of the gut during the examined time span. The variances in the number of NF-positive neurons were not homogeneous, and the data were therefore not suitable for ANOVA. Accordingly, only semiquantitative conclusions could be drawn.

Tenascin differentiates dermatofibroma from dermatofibrosarcoma protuberans: comparison with CD34 and factor XIIIa.

Differentiation of dermatofibroma (DF) from dermatofibrosarcoma protuberans (DFSP) can be difficult. CD34 and Factor XIIIa have been used to differentiate DF from DFSP. However, there is overlap and lack of specificity of their expression. Tenascin is an extracellular matrix glycoprotein that is involved in embryogenesis, carcinogenesis, and wound healing. The aim of the study was to assess the role of tenascin in DF and DFSP and compare the results with those obtained with CD34 and Factor XIIIa. Immunohistochemical staining was performed on 20 cases each of DFSP and DF, using antibodies to tenascin, CD34 and Factor XIIIa, and the streptavidin biotin technique. Positivity for all 3 antibodies was assessed within the tumors. Tenascin expression was also assessed at the dermal-epidermal junction. Strong tenascin positivity was noted at the dermal-epidermal junction overlying the lesion in 20 of 20 cases of DF (100%) and was negative over the lesion in 20 of 20 cases DFSP (100%). Tenascin was noted within the lesion of 80% of both DF and DFSP (16/20 cases). CD34 was strongly expressed in 16 of 20 (80%) DFSP and 5 of 20 (25%) DF, whereas Factor XIIIa was strongly expressed in 19 of 20 (95%) DF and 3 of 15 (15%) DFSP. Although CD34 was expressed in 80% DFSP and Factor XIIIa in 95% of DF, there was overlap in their expression in the 2 types of tumors. The increased expression of tenascin at the dermal-epidermal junction overlying the lesion in DF but not in DFSP, differentiated these 2 tumors. In contrast, tenascin expression within the lesion did not differentiate DF from DFSP.

The biochemistry of citric acid accumulation by Aspergillus niger.

Fungi, in particular Aspergilli, are well known for their potential to overproduce a variety of organic acids. These microorganisms have an intrinsic ability to accumulate these substances and it is generally believed that this provides the fungi with an ecological advantage, since they grow rather well at pH 3 to 5, while some species even tolerate pH values as low as 1.5. Organic acid production can be stimulated and in a number of cases conditions have been found that result in almost quantitative conversion of carbon substrate into acid. This is exploited in large-scale production of a number of organic acids like citric-, gluconic- and itaconic acid. Both in production volume as well as in knowledge available, citrate is by far the major organic acid. Citric acid (2-hydroxy-propane-1,2,3-tricarboxylic acid) is a true bulk product with an estimated global production of over 900 thousand tons in the year 2000. Till the beginning of the 20th century, it was exclusively extracted from lemons. Since the global market was dominated by an Italian cartel, other means of production were sought. Chemical synthesis was possible, but not suitable due to expensive raw materials and a complicated process with low yield. The discovery of citrate accumulation by Aspergillus niger led to a rapid development of a fermentation process, which only a decade later accounted for a large part of the global production. The application of citric acid is based on three of its properties: (1) acidity and buffer capacity, (2) taste and flavour, and (3) chelation of metal ions. Because of its three acid groups with pKa values of 3.1, 4.7 and 6.4, citrate is able to produce a very low pH in solution, but is also useful as a buffer over a broad range of pH values (2 to 7). Citric acid has a pleasant acid taste which leaves little aftertaste. It sometimes enhances flavour, but is also able to mask sweetness, such as the aspartame taste in diet beverages. Chelation of metal ions is a very important property that has led to applications such as antioxidant and preservative. Moreover, it is a "natural" substance and fully biodegradable.

Reduced (1)H-NMR visibility of creatine in isolated rat hearts.

The aim of this study was to measure the concentration of creatine in Langendorff perfused rat hearts, both by quantitative (1)H-MRS and by high-pressure liquid chromatography (HPLC). First, the relaxation times and other parameters affecting absolute quantification by MRS were determined. At 11.75 T, the relaxation times of myocardial creatine were T(1) = 1.1+/-0.29 sec (mean +/- SD, n = 5) and T(2) = 56.4+/-6.2 ms (n = 9). In phantom experiments the MRS measurements gave accurate values for the known relative concentrations of the detected substances. In glucose-perfused rat hearts, the creatine concentration measured by HPLC was 14.2+/-1.9 mmol/kg wet weight (n = 8), in good agreement with literature values. The (1)H-MRS measurements, however, resulted in creatine concentrations of only approximately 60% of this value. The application of CHESS-pulses for water suppression led to a further 30% reduction of the creatine MRS signal. These results indicate a reduced (1)H-NMR visibility of creatine in the myocardium, which suggests a compartmentation of myocardial creatine into various pools.

Immunological importance of chimerism in transplantation: new conditioning protocol in BMT and the development of chimeric state.

Chimerism is an exceptional immunogenetic state, characterized by the survival and collaboration of cell populations originated from two different individuals. The prerequisits to induce chimerism are immuno-suppression, myeloablation, or severe immunodeficiency of the recipients on the one side and donor originated immuno-hematopoietic cells in the graft on the other. The pathologic or special immunogenetic conditions to establish chimerism are combined with bone marrow transplantation, transfusion, and various kinds of solid organ grafting. Different types of chimerism are known including complete, mixed and mosaic, or split chimerism. There are various methods used to detect the type of chimera state, depending on the immunogenetic differences between the donor and recipient. The induction of complete or mixed chimerism is first determinated by the effect of myeloablative therapy. The chimera state seems to be one of the leading factors to influence the course of the post-transplant period, the frequency and severity of GVHD, and the rate of relapse. However, the most important contribution of the chimeric state is in development of graft versus leukemia effect. A new conditioning protocol (DBM/Ara-C/Cy) for allogeneic BMT in CML patients and its consequence on chimera state and GVL effect is demonstrated.

Quantitative distribution of NADPH-diaphorase-positive myenteric neurons in different segments of the developing chicken small intestine and colon.

NADPH-diaphorase (NADPH-d) was used as a marker for neuronal nitric oxide synthase in order to investigate the nitrergic neurons of the developing myenteric ganglia on whole-mount preparations in the proximal and distal segments of the small intestine and in the colon of the chicken embryo, between incubation days 12 and 19. Neurons that were positive for NADPH-d were counted in randomly selected myenteric ganglia. The data obtained from each area and each age group were subjected to two-way analysis of variance (ANOVA) and the Student-Newman-Keuls test. Between incubation days 12 and 19, the originally narrow-meshed myenteric plexus with its high ganglionic density progressively became wide-meshed and the ganglionic density decreased significantly. Quantitative analysis further revealed a significant decrease in the NADPH-d-positive nerve cell density with age. At the same time, the constant or even increasing number of nitrergic cells per ganglion may indicate that the decreasing cell density may be a result of the growth of the bowel with decreasing ganglion density rather than a decrease in the total number of myenteric nitrergic cells. Regional differences in the dynamics of the quantitative changes were revealed. A significant decrease in the nitrergic cell number appeared earlier in the proximal than in the distal segments of the small intestine or in the colon. In contrast, the significant decline of the ganglionic density was first noticed in the colon at the same time.