Pathohistological study of the ganglion plexuses of the sigmoid colon in patients with chronic slow-transit constipation

The morphological study of the resected sections of the colon obtained at the S.P. Fedorov Department of Faculty Surgery of S.M. Kirov Military Medical Academy, as a result of surgical treatment of patients with severe chronic slow-transit constipation, included an assessment of the changes in the structures of ganglion plexuses. Three cases were considered (women, aged 3740 years). Various degrees of pathological changes were detected in the ganglion plexuses (Auerbach and Meissner) of the sigmoid colon from patients with chronic slow-transit constipation using Nissls toluidine blue staining. In all cases, reactive, dystrophic, severe degenerative-necrotic changes of ganglion cells, as well as the details of their death, were described in detail. Along with pathological changes in nerve cells in the myenteric nerve plexus and gliosis, features of neuronglial relationships were described, and the death of ganglion cells in the human colon with the active participation of specialized astrocyte-like glial cells was also established for the first time. In the third case, a pattern of pronounced dysplasia and dysgangliogenesis was revealed in the myenteric ganglion plexus of the sigmoid colon, and the presence of diffuse lymphmonocytic infiltrates was noted in the circular muscle layer. Pathological changes in the enteral nervous system in chronic slow-transit constipation reflect neuropathy, which can serve as the main cause of impaired intestinal functions and of some symptoms.

Larger muscle fibers and fiber bundles manifest smaller elastic modulus in paraspinal muscles of rats and humans

The passive elastic modulus of muscle fiber appears to be size-dependent. The objectives of this study were to determine whether this size effect was evident in the mechanical testing of muscle fiber bundles and to examine whether the muscle fiber bundle cross-section is circular. Muscle fibers and fiber bundles were extracted from lumbar spine multifidus and longissimus of three cohorts: group one (G1) and two (G2) included 13 (330 ± 14 g) and 6 (452 ± 28 g) rats, while Group 3 (G3) comprised 9 degenerative spine patients. A minimum of six muscle fibers and six muscle fiber bundles from each muscle underwent cumulative stretches, each of 10% strain followed by 4 minutes relaxation. For all specimens, top and side diameters were measured. Elastic modulus was calculated as tangent at 30% strain from the stress–strain curve. Linear correlations between the sample cross sectional area (CSA) and elastic moduli in each group were performed. The correlations showed that increasing specimen CSA resulted in lower elastic modulus for both rats and humans, muscle fibers and fiber bundles. The median ratio of major to minor axis exceeded 1.0 for all groups, ranging between 1.15–1.29 for fibers and 1.27–1.44 for bundles. The lower elastic moduli with increasing size can be explained by relatively less collagenous extracellular matrix in the large fiber bundles. Future studies of passive property measurement should aim for consistent bundle sizes and measuring diameters of two orthogonal axes of the muscle specimens.

Cocaine and Amphetamine Regulated Transcript (CART) Expression Changes in the Stomach Wall Affected by Experimentally Induced Gastric Ulcerations

Cocaine- and amphetamine-regulated transcript (CART) is a peptide suggested to play a role in gastrointestinal tract tissue reaction to pathology. Gastric ulceration is a common disorder affecting huge number of people, and additionally, it contributes to the loss of pig livestock production. Importantly, ulceration as a focal disruption affecting deeper layers of the stomach wall differs from other gastrointestinal pathologies and should be studied individually. The pig’s gastrointestinal tract, due to its many similarities to the human counterpart, provides a valuable experimental model for studying digestive system pathologies. To date, the role of CART in gastric ulceration and the expression of the gene encoding CART in porcine gastrointestinal tube are completely unknown. Therefore, we aimed to verify the changes in the CART expression by Q-PCR (gene encoding CART in the tissue) and double immunofluorescence staining combined with confocal microscopy (CART immunofluorescence in enteric nervous system) in the porcine stomach tissues adjacent to gastric ulcerations. Surprisingly, we found that gastric ulcer caused a significant decrease in the expression of CART-encoding gene and huge reduction in the percentage of CART-immunofluorescent myenteric perikarya and neuronal fibers located within the circular muscle layer. Our results indicate a unique CART-dependent gastric response to ulcer disease.

Role of PGE2 in colonic motility: PGE2 attenuates spontaneous contractions of circular smooth muscle via EP4 receptors in the rat colon

Colonic motor activity is important for the formation and propulsion of feces. The production of prostaglandins (PGs) in colonic tissue is considered to play a critical role in the generation and regulation of colonic motility. In this study, we investigated the inhibitory effects of PGE2 and selective agonists of four EP receptors on the spontaneous phasic contractions, called ‘giant contractions’ (GCs), of mucosa-free circular smooth muscle strips from the rat middle colon. Neural blockade with tetrodotoxin (TTX) increased the frequency and amplitude of the GCs by about twofold. However, inhibiting PG production with piroxicam reduced the GC frequency in the presence of TTX, but did not affect the GC amplitude. In the presence of both TTX and piroxicam, exogenous PGE2 and each EP receptor agonist were cumulatively added to the tissue bath. In this setting, PGE2, the EP2 agonist ONO-AE1-259, and the EP4 agonist ONO-AE1-329, but not the EP1 agonist ONO-AE-DI-004 or the EP3 agonist ONO-AE-248, concentration-dependently reduced the GC frequency and amplitude. The PGE2-induced inhibition of GC frequency and amplitude was inhibited by the EP4 antagonist ONO-AE3-208, but not by the EP1/2 antagonist AH6809. Immunohistochemistry revealed the EP2 and EP4 receptors were localized in perinuclear sites in circular smooth muscle cells. EP2 immunoreactivity was also located in GFAP-immunoreactive enteroglia, whereas EP4 immunoreactivity was also located in HU (embryonic lethal, abnormal vision [ELAV] protein; a marker of all myenteric neurons)-immunoreactive myenteric nerve cell bodies. These results suggest that the PGs produced in the colonic tissue inhibit the GC frequency and amplitude of circular muscle in the rat middle colon, and is mediated by EP4 receptors expressed in the smooth muscle cells.

The distribution pattern of periprostatic neurovascular bundles examined with successive celloidin slices

Background Although several distribution patterns of periprostatic neurovascular bundles have been proposed, variant dissection technique based on these patterns still confused surgeons. The aim of this study was to describe the periprostatic neurovascular bundles and their relationship with the fascicles around prostate and provide the accurate morphologic knowledge of periprostatic tissue for prostate operation. Methods The pelvic viscera were obtained from 26 adult male cadavers. They were embedded in celloidin and cut into successive slices. The slices were explored with anatomic microscopy. 3-Dimensional reconstruction was achieved with celloidin sections and series software. Results The prostatic capsule which surrounded the dorsal, bilateral aspect of the prostate was attached ventrally to anterior fibrous muscular stroma (AFMS). The lower part of the striated sphincter completely embraced the urethral; the upper part of this muscle covered the lower ventral surface of prostate. The upper ventral surface of prostate is covered by the circular muscle of detrusor. The levator fascia and the capsule adhered on the most convex region of the lateral prostate, but separated on the other region. The pelvic neurovascular bundles (PNVB) divided into the anterior and posterior divisions. The anterior division continued as dorsal vascular complex (DVC). The distal part of DVC entered into penile hilum. The posterior division continued as neurovascular bundles, and then as the cavernous supply (CS). The distal part of CS joined into pudendal neurovascular bundles. Conclusions The capsule and AFMS formed a pocket like complex. There were anterior and posterior neurovascular approaches from PNVB to penile hilum.

Inducible heat shock protein A1A (HSPA1A) is markedly expressed in rat myometrium by labour and secreted via myometrial cell-derived extracellular vesicles

The myometrium goes through physiological, cellular and molecular alterations during gestation that necessitate effective cellular proteostasis. Inducible heat shock protein A1A (HSPA1A) is a member of the 70-kDa heat shock protein A (HSPA) family, which acts as a chaperone to regulate proteostasis; however, HSPA1A also participates as a cytokine in inflammatory regulation, leading to its designation as a chaperokine. This study examined the spatiotemporal expression of HSPA1A protein in the rat myometrium throughout gestation and assessed whether it is secreted as cargo of myometrial cell-derived extracellular vesicles (EVs). Immunoblot analysis demonstrated that HSPA1A expression was markedly elevated during late pregnancy and labour and increased by uterine distension. Myometrial HSPA1A expression insitu increased in myocytes of longitudinal and circular muscle layers from Day 19 through to postpartum, specifically in the cytoplasm and nuclei of myocytes from both muscle layers, but frequently detectable just outside myocyte membranes. Scanning electron microscopy examination of samples isolated from hTERT-HM cell-conditioned culture medium, using EV isolation spin columns, confirmed the presence of EVs. EV lysates contained HSPA8, HSPA1A and the EV markers apoptosis-linked gene 2-interacting protein X (Alix), the tetraspanin cluster of differentiation 63 (CD63), tumour susceptibility gene 101 (TSG101) and HSP90, but not the endoplasmic reticulum protein calnexin. These results indicate that HSPA1A may act as a chaperokine in the myometrium during pregnancy.

The Distribution Pattern of Periprostatic Neurovascular Bundles Examined with Successive Celloidin Slices

Background: Although several distribution patterns of periprostatic neurovascular bundles have been proposed, variant dissection technique based on these patterns still confused surgeons.The aim of this study was to describe the periprostatic neurovascular bundles and their relationship with the fascicles around prostate and provide the accurate morphologic knowledge of periprostatic tissue for prostate operation.Methods: The pelvic viscera were obtained from 26 adult male cadavers. They were embedded in celloidin and cut into successive slices. The slices were explored with anatomic microscopy. 3-Dimensional reconstruction was achieved with celloidin sections and series software.Results: The prostatic capsule which surrounded the dorsal, bilateral aspect of the prostate was attached ventrally to anterior fibrous muscular stroma (AFMS). The lower part of the striated sphincter completely embraced the urethral; the upper part of this muscle covered the lower ventral surface of prostate. The upper ventral surface of prostate is covered by the circular muscle of detrusor. The levator fascia and the capsule adhered on the most convex region of the lateral prostate, but separated on the other region. The pelvic neurovascular bundles (PNVB) divided into the anterior and posterior divisions. The anterior division continued as dorsal vascular complex (DVC). The distal part of DVC entered into penile hilum. The posterior division continued as neurovascular bundles NVB, and then as the cavernous supply (CS). The distal part of CS joined into pudendal neurovascular bundles. Conclusions: The capsule and AFMS formed a pocket like complex. There were anterior and posterior neurovascular approaches from PNVB to penile hilum.

Clinical and Histopathological Spectrum of Adult Gastrointestinal Inflammatory Neuropathy

Gastrointestinal inflammatory neuropathy, namely, eosinophilic myenteric ganglioneuronitis (EMG) and lymphocytic ganglioneuronitis (LG), is a form of chronic intestinal pseudo-obstruction and results from the infiltration of the myenteric plexus by eosinophils and lymphocytes, respectively. The literature related to the clinicopathological features of adult inflammatory neuropathy is scarce. We aim to elucidate the clinical and histological details of 7 cases of inflammatory neuropathy (EMG, n = 4, and LG, n = 3) and compare the features of EMG and LG retrospectively. There was no difference between these two entities in terms of clinical, hematological, or biochemical parameters. Histologically, almost all cases (n = 6/7) showed accompanying elements of ganglion cell vacuolization, mesenchymopathy, and partial/complete desmosis in addition to the disease-defining pathology. Besides, all cases of EMG showed infiltration of the inner circular muscle of muscularis propria by eosinophils. Two cases of LG showed additional muscular pathology pertaining to the muscularis propria. Inflammatory infiltration of the myenteric plexus is pathognomonic for the diagnosis of gastrointestinal inflammatory neuropathy although additional features in the form of ganglion cell vacuolization, reduction in the number of ganglia, desmosis, mesenchymopathy, and inflammation of the muscularis propria (eosinophils in EMG) can be seen. The pathologists need proper awareness along with judicious use of special and immunostains for clinching the diagnosis.