Dysfunction of specific auditory fibers impacts cortical oscillations, driving an autism phenotype despite near-normal hearing.

Autism spectrum disorder is discussed in the context of altered neural oscillations and imbalanced cortical excitation-inhibition of cortical origin. We studied here whether developmental changes in peripheral auditory processing, while preserving basic hearing function, lead to altered cortical oscillations. Local field potentials (LFPs) were recorded from auditory, visual, and prefrontal cortices and the hippocampus of BdnfPax2 KO mice. These mice develop an autism-like behavioral phenotype through deletion of BDNF in Pax2+ interneuron precursors, affecting lower brainstem functions, but not frontal brain regions directly. Evoked LFP responses to behaviorally relevant auditory stimuli were weaker in the auditory cortex of BdnfPax2 KOs, connected to maturation deficits of high-spontaneous rate auditory nerve fibers. This was correlated with enhanced spontaneous and induced LFP power, excitation-inhibition imbalance, and dendritic spine immaturity, mirroring autistic phenotypes. Thus, impairments in peripheral high-spontaneous rate fibers alter spike synchrony and subsequently cortical processing relevant for normal communication and behavior.

Changes in myelinated nerve fibers induced by pulsed electrical stimulation: A microstructural perspective on the causes of electrical stimulation side effects.

Electrical brain stimulation technology is widely used in the clinic to treat brain neurological disorders. However, during treatment, patients may experience side effects such as pain, poor limb coordination, and skin rash. Previous reports have focused on the brilliant chapter on electrical brain stimulation technology and have not paid attention to patients' suffering caused by side effects during treatment. In this study, electrodes were arranged on the medulla oblongata. Pulsed electric fields of different frequencies were used to perform electrical stimulation to study the impact of electric fields on myelinated nerve fibers and reveal the possible microstructural origin of side effects. Transmission electron microscopy was used to analyze and quantify the changes in microstructure. The results illustrated that myelinated nerve fibers underwent atrophy under pulsed electric fields, with the mildest degree of atrophy under high-frequency (400 Hz) electric fields. Myelin sheaths experienced plate separation under pulsed electric fields, and a distinct laminar structure appeared. The microstructure changes may be related to the side effects of clinical electrical stimulation. This study can provide pathological possibilities for exploring the causes of the side effects of electrical stimulation and supply guidance for selecting electrical parameters for clinical electrical stimulation therapy from a distinctive perspective.

Zinc deficiency triggers hearing loss by reducing ribbon synapses of inner hair cells in CBA/N mice.

Zinc plays a vital role in our metabolism, encompassing antioxidant regulation, immune response, and auditory function. Several studies have reported that zinc levels correlate with hearing loss. We have previously demonstrated that the auditory brainstem response (ABR) threshold increased in mice fed a zinc-deficient diet. However, the effects of zinc deficiency on hearing were not fully elucidated. The present study investigated whether zinc deficiency affects hearing in association with neuronal components or cochlear structures. CBA/N mice were fed a normal or zinc-deficient diet for 8 weeks and assessed for ABR and distortion product otoacoustic emissions (DPOAE). The cochlear sections were stained with hematoxylin and eosin solution. Also, we observed the expression of synaptic ribbons, neurofilaments, and alpha-synuclein (α-Syn). The 8-week zinc-deficient diet mice had an elevated ABR threshold but no changed DPOAE threshold or cochlear structures. A reduced number of synaptic ribbons of inner hair cells (IHCs) and impaired efferent nerve fibers were observed in the zinc-deficient diet mice. The number of outer hair cells (OHCs) and expression of α-Syn remained unchanged. Our results suggest that zinc-mediated hearing loss is associated with the loss of neuronal components of IHCs.

Disease activity in chronic inflammatory demyelinating polyneuropathy: association between circulating B-cell subsets, cytokine levels, and clinical outcomes.

Chronic inflammatory demyelinating polyneuropathy (CIDP), a common and treatable autoimmune neuropathy, is frequently misdiagnosed. The aim of this study is to evaluate the relationship between immunological markers and clinical outcome measures in a mixed cohort of patients with typical CIDP and CIDP variants at different disease stages. Twenty-three typical, 16 multifocal and five distal CIDP patients were included. Twenty-five sex and age-matched healthy controls and 12 patients with Charcot-Marie-Tooth type 1A (CMT1A) disease served as controls. Peripheral B-cell populations were analyzed by flow cytometry. IL6, IL10, TNFA mRNA and mir-21, mir-146a, and mir-155-5p expression levels were evaluated by real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMC) and/or skin biopsy specimens. Results were then assessed for a possible association with clinical disability scores and intraepidermal nerve fiber densities (IENFD) in the distal leg. We detected a significant reduction in naive B cells (P ≤ 0.001), plasma cells (P ≤ 0.001) and regulatory B cells (P < 0.05), and an elevation in switched memory B cells (P ≤ 0.001) in CIDP compared to healthy controls. CMT1A and CIDP patients had comparable B-cell subset distribution. CIDP cases had significantly higher TNFA and IL10 gene expression levels in PBMC compared to healthy controls (P < 0.05 and P ≤ 0.01, respectively). IENFDs in the distal leg showed a moderate negative correlation with switched memory B-cell ratios (r = -0.51, P < 0.05) and a moderate positive correlation with plasma cell ratios (r = 0.46, P < 0.05). INCAT sum scores showed a moderate positive correlation with IL6 gene expression levels in PBMC (r = 0.54, P < 0.05). Altered B-cell homeostasis and IL10 and TNFA gene expression levels imply chronic antigen exposure and overactivity in the humoral immune system, and seem to be a common pathological pathway in both typical CIDP and CIDP variants.

Taste Bud Connectome: Implications for Taste Information Processing.

Taste buds contain multiple cell types, two of which mediate transduction of specific taste qualities: Type III cells transduce sour while Type II cells transduce either sweet, or bitter or umami. In order to discern the degree of interaction between different cell types and specificity of connectivity with the afferent nerve fibers (NFs), we employed serial blockface scanning electron microscopy (sbfSEM) through five circumvallate mouse taste buds. Points of contact between Type II and Type III cells are rare and lack morphologically identifiable synapses, suggesting that interaction between these cell types does not occur via synapses. Of the 127 NFs that make synaptic contacts with taste cells in the sampling volume, ∼70% (n = 91) synapse with only one taste cell while 32 fibers synapse exclusively with multiple Type II cells or multiple Type III cells. Our data do not rule out multimodal fibers innervating Type II cells of separate taste qualities. Notably, four fibers (∼3%) synapse with both Type II and Type III cells, forming both mitochondrial and vesicular synapses on the different cell types. Since Type II and Type III cells transduce different taste qualities, these dual connected fibers are not consistent with a absolute labeled-line encoding system. Further, our data reveal considerable variation in both the number of synapses per cell/nerve pair and the number of innervating NFs per taste cell, both of which likely have consequences for encoding taste quality and concentration. Finally, we identify a subset of Type II cells which may represent an immature stage.SIGNIFICANCE STATEMENT Taste buds, the sensory end organs for the sense of taste, contain multiple types of sensory cells, with each responding to one of the primary tastes: salt, sweet, sour, bitter, and umami. In order to determine the degree of interaction between cell types and specificity of connectivity to afferent nerves, we employed serial blockface electron microscopy (EM) of mouse circumvallate taste buds. We find no synapses between cell types within the taste bud suggesting that any interactions are indirect. While the majority of nerve fibers (NFs) connect to a single type of taste cell, 3.1% of the fibers branch to receive input from taste cells of different specificities. Thus, taste cannot entirely be carried along NFs dedicated to single taste qualities.

Human pancreatic capillaries and nerve fibers persist in type 1 diabetes despite beta cell loss.

The autonomic nervous system regulates pancreatic function. Islet capillaries are essential for the extension of axonal projections into islets, and both of these structures are important for appropriate islet hormone secretion. Because beta cells provide important paracrine cues for islet glucagon secretion and neurovascular development, we postulated that beta cell loss in type 1 diabetes (T1D) would lead to a decline in intraislet capillaries and reduction of islet innervation, possibly contributing to abnormal glucagon secretion. To define morphological characteristics of capillaries and nerve fibers in islets and acinar tissue compartments, we analyzed neurovascular assembly across the largest cohort of T1D and normal individuals studied thus far. Because innervation has been studied extensively in rodent models of T1D, we also compared the neurovascular architecture between mouse and human pancreas and assembled transcriptomic profiles of molecules guiding islet angiogenesis and neuronal development. We found striking interspecies differences in islet neurovascular assembly but relatively modest differences at transcriptome level, suggesting that posttranscriptional regulation may be involved in this process. To determine whether islet neurovascular arrangement is altered after beta cell loss in T1D, we compared pancreatic tissues from non-diabetic, recent-onset T1D (<10-yr duration), and longstanding T1D (>10-yr duration) donors. Recent-onset T1D showed greater islet and acinar capillary density compared to non-diabetic and longstanding T1D donors. Both recent-onset and longstanding T1D had greater islet nerve fiber density compared to non-diabetic donors. We did not detect changes in sympathetic axons in either T1D cohort. Additionally, nerve fibers overlapped with extracellular matrix (ECM), supporting its role in the formation and function of axonal processes. These results indicate that pancreatic capillaries and nerve fibers persist in T1D despite beta cell loss, suggesting that alpha cell secretory changes may be decoupled from neurovascular components.NEW & NOTEWORTHY Defining the neurovascular architecture in the pancreas of individuals with type 1 diabetes (T1D) is crucial to understanding the mechanisms of dysregulated glucagon secretion. In the largest T1D cohort of biobanked tissues analyzed to date, we found that pancreatic capillaries and nerve fibers persist in human T1D despite beta cell loss, suggesting that alpha cell secretory changes may be decoupled from neurovascular components. Because innervation has been studied extensively in rodent T1D models, our studies also provide the first rigorous direct comparisons of neurovascular assembly in mouse and human, indicating dramatic interspecies differences.

Statistical modeling of diabetic neuropathy: Exploring the dynamics of nerve mortality.

Diabetic neuropathy is a disorder characterized by impaired nerve function and reduction of the number of epidermal nerve fibers per epidermal surface. Additionally, as neuropathy related nerve fiber loss and regrowth progresses over time, the two-dimensional spatial arrangement of the nerves becomes more clustered. These observations suggest that with development of neuropathy, the spatial pattern of diminished skin innervation is defined by a thinning process which remains incompletely characterized. We regard samples obtained from healthy controls and subjects suffering from diabetic neuropathy as realisations of planar point processes consisting of nerve entry points and nerve endings, and propose point process models based on spatial thinning to describe the change as neuropathy advances. Initially, the hypothesis that the nerve removal occurs completely at random is tested using independent random thinning of healthy patterns. Then, a dependent parametric thinning model that favors the removal of isolated nerve trees is proposed. Approximate Bayesian computation is used to infer the distribution of the model parameters, and the goodness-of-fit of the models is evaluated using both non-spatial and spatial summary statistics. Our findings suggest that the nerve mortality process changes as neuropathy advances.

Retinal changes in generalized anxiety disorder patients.

OBJECTIVE: Optical coherence tomography (OCT) is a method that allows high-resolution cross-sectional imaging of biological tissues. It was suggested that changes in the cranial structure or functions would be reflected in the retina. OCT has been an important method in the diagnosis and follow-up of diseases via morphometric or quantitative retinal measurements. Free radicals, inflammatory processes, and neurotransmission disorders play a role in the etiology of generalized anxiety disorder (GAD). The study aimed to demonstrate the retinal changes in GAD patients due to neurodegeneration based on the comparison of the OCT data of the GAD patients and controls, and the differences between OCT findings of GAD patients and those of controls. METHODS: The study group included 21 GAD patients. The control group included 21 individuals without any known psychiatric or organic disease, including eye diseases. RESULTS: There was a statistically significant difference between the macular volumes (MV) of the GAD and control groups, the macular volume was lower in the GAD group. There were positive correlations between BDI scores and MV, GCLT, RNFLT-i, RNFLT-n, between BAE scores and (RNFLT-n), and between the CGI severity scale scores and MV, RNFLT-n, and RNFLT-t. CONCLUSION: OCT analysis of the GAD patients demonstrated that MV values were lower when compared to the control group. Patients with GAD should be screened for these retinal changes. OCT, a simple, non-invasive, and relatively inexpensive method could be employed as a supplementary method in the follow-up of GAD patients.

Connections between postparotid terminal branches of the facial nerve: An immunohistochemistry study.

It has been assumed that connections between the postparotid terminal branches of the facial nerve are purely motor. However, the nature of their fibers remains unexplored. The aim of this study is to determine whether these connections comprise motor fibers exclusively. In total 17 connections between terminal facial nerve branches were obtained from 13 different facial nerves. Choline acetyltransferase antibody (ChAT) was used to stain the fibers in the connections and determine whether or not all of them were motor. All connections contained ChAT positive and negative fibers. The average number of fibers overall was 287 (84-587) and the average proportion of positive fibers was 63% (37.7%-91.5%). In 29% of the nerves, >75% of the fibers were ChAT+ (strongly positive); in 52.94%, 50%-75% were ChAT+ (intermediately positive); and in 17.65%, <50% were ChAT+ (weakly positive). Fibers traveling inside the postparotid terminal cranial nerve VII branch connections are not exclusively motor.

[Confocal microscopy of the corneal nerve fibers]. / Konfokal'naya mikroskopiya nervnykh volokon rogovitsy.

This article presents the results of confocal microscopy of the corneal nerve fibers (CNF). The transparency of the cornea provides a unique potential for in vivo visualization of thin unmyelinated nerve fibers at the level close to morphological study. Modern software eliminates the need for manual tracing of the confocal image fragments, allows objectifying the process of assessment of CNF structure based on quantitative indicators characterizing the length, density and tortuosity of the main nerve trunks. Clinical application of structural analysis of the CNF has two potential directions associated with immediate tasks of ophthalmology, as well as with interdisciplinary affairs. In terms of ophthalmology, this primarily concerns various surgical interventions potentially affecting the state of the cornea, and chronic pathological processes in the cornea of different nature. Such studies could analyze the degree of changes in the CNF, or the particularities of corneal reinnervation. The potential for interdisciplinary studies lies in using CNF as biomarkers of systemic polyneuropathies. Relative simplicity, high level of direct visualization of the thin nerve fibers, and the obtained results allow recommending corneal confocal microscopy as a tool for primary screening and consequent monitoring of neuropathies in addition to the conventional methods.

[Hybrid (femtolaser) phacoemulsification: technical aspects and functional results]. / Gibridnaya (femtolazernaya) fakoemul'sifikatsiya: tekhnologicheskie aspekty i funktsional'nye rezul'taty.

This article summarizes scientific and practical results of hybrid femtosecond laser-assisted phacoemulsification (HFE) including study of clinical and technical aspects of the intervention and evaluation of post-surgical functional state of the eye on the basis of clinical, morphological and biomechanical data. The HFE technology should be considered the method of choice for microinvasive phaco surgery, its main advantage being the possibility of controlled handling of such important surgical stages as anterior circular continuous capsulorhexis and nucleus fragmentation on a closed eyeball, which significantly reduces the risk of complications and decreases of effective ultrasound time.

Multifunctional Immunoliposomes Enhance the Immunotherapeutic Effects of PD-L1 Antibodies against Melanoma by Reprogramming Immunosuppressive Tumor Microenvironment.

The immunosuppressive tumor microenvironment (TME) can significantly limit the immunotherapeutic effects of the PD-L1 antibody (aPDL1) by inhibiting the infiltration of CD8+ cytotoxic T cells (CTLs) into the tumor tissues. However, how to reprogram the immunosuppressive TME and promote the infiltration of CTLs remains a huge challenge for aPDL1 to achieve the maximum benefits. Herein, the authors design a multifunctional immunoliposome that encapsulates the adrenergic receptor blocker carvedilol (CAR) and connects the "don't eat me" signal antibody (aCD47) and aPDL1 in series via a reactive oxygen species (ROS)-sensitive linker on the surface. In ROS-enriched immunosuppressive TME, the multifunctional immunoliposome (CAR@aCD47/aPDL1-SSL) can first release the outer aCD47 to block the "do not eat me" pathway, promote the phagocytosis of tumor cells by phagocytic cells, and activate CTLs. Then, the aPDL1 on the liposome surface is exposed to block the PD-1/PD-L1 signaling pathway, thereby inducing CTLs to kill tumor cells. CAR encapsulated in CAR@aCD47/aPDL1-SSL can block the adrenergic nerves in the tumor tissues and reduce their densities, thereby inhibiting angiogenesis in the tumor tissues and reprogramming the immunosuppressive TME. According to the results, CAR@aCD47/aPDL1-SSL holds an effective way to reprogram the immunosuppressive TME and significantly enhance immunotherapeutic efficiency of aPDL1 against the primary cancer and metastasis.

Disease activity in chronic inflammatory demyelinating polyneuropathy: A comparative study of clinical and skin biopsy markers.

INTRODUCTION/AIMS: Epidermal nerve fiber involvement in chronic inflammatory demyelinating neuropathy (CIDP) has been reported in a limited number of patients. We quantified small-fiber involvement in a mixed cohort of patients with typical CIDP and CIDP variants to evaluate relationships with clinical outcome measures at different disease stages. METHODS: Intraepidermal nerve fiber densities (IENFDs) were evaluated by skin punch biopsies of 23 patients with CIDP and 13 healthy controls at the forearm, thigh, and distal leg. Skin sections were optimally interpreted in all three regions in 16 CIDP patients and 10 age- and sex-matched healthy controls. Statistical analysis was performed in these subjects. RESULTS: The IENFDs in forearm, thigh, and distal leg were similar among seven typical CIDP and nine CIDP variants. IENFDs in those regions were significantly reduced in CIDP compared with healthy controls, with a moderate negative correlation with scores on the International Neuropathy Cause and Treatment (INCAT) Upper Limb Functional Disability Scale. The reduction in IENFD compared with controls was more remarkable in the distal leg. In clinically unstable CIDP patients, the IENFDs of distal leg and forearm were significantly reduced compared with stable CIDP patients and controls. Stable CIDP patients had significantly reduced IENFDs in distal leg and forearm compared with controls. DISCUSSION: In this exploratory study, we confirm that small fibers are also affected in CIDP. Larger studies are needed to explore longitudinal changes of IENFD in CIDP and its relation to disease stage.

Selective electrical stimulation of low versus high diameter myelinated fibers and its application in pain relief: a modeling study.

Electrical stimulation of peripheral nerve fibers has always been an attractive field of research. Due to the higher activation threshold, the stimulation of small fibers is accompanied by the stimulation of larger ones. It is therefore necessary to design a specific stimulation theme in order to only activate narrow fibers. There is evidence that stimulating Aδ fibers can activate endogenous pain-relieving mechanisms. However, both selective stimulation and reducing pain by activating small nociceptive fibers are still poorly investigated. In this study, using high-frequency stimulation waveforms (5-20 kHz), computational modeling provides a simple framework for activating narrow nociceptive fibers. Additionally, a model of myelinated nerve fibers is modified by including sodium-potassium pump and investigating its effects on neuronal stimulation. Besides, a modified mathematical model of pain processing circuits in the dorsal horn is presented that consists of supraspinal pain control mechanisms. Hence, by employing this pain-modulating model, the mechanism of the reduction of pain by activating nociceptive fibers is explored. In the case of two fibers with the same distance from the point source electrode, a single stimulation waveform is capable of blocking one large fiber and stimulating another small fiber. Noteworthy, the Na/K pump model demonstrated that it does not have a significant effect on the activation threshold and firing frequency of fiber. Ultimately, results suggest that the descending pathways of Locus coeruleus may effectively contribute to pain relief through stimulation of nociceptive fibers, which will be beneficial for clinical interventions.

Assessment of Nerve Fiber Density and Expression of Hormonal Receptors Within Rectosigmoid Endometriosis Nodules.

STUDY OBJECTIVE: To assess nerve fiber density and expression of hormone receptors in bowel endometriosis. DESIGN: Cross-sectional study. SETTING: Private hospital. PATIENTS: Women with endometriosis undergoing laparoscopic segmental bowel resection (n = 54). INTERVENTIONS: Tissue samples were obtained from patients with surgically treated rectosigmoid endometriosis. MEASUREMENTS AND MAIN RESULTS: The rectosigmoid specimen containing the endometriosis nodule was manually sectioned and divided into 3 areas: core of the nodule, margin of the nodule, and healthy bowel tissue. The intensity of expression of estrogen and progesterone receptors was evaluated by immunohistochemistry and measured according to the Allred score. Nerve fibers were stained by immunohistochemistry using Protein Gene Product 9.5, and the density of nerve fillets was counted and expressed in number/mm². All glandular and stromal cells stained for estrogen; however, glandular cells stained more strongly than stromal cells (61.1% vs 35.2%; p = .01). Most of glandular and stromal cells stained strongly for progesterone receptors (90.7% vs 98.1%; p = .2). The density of nerve fibers was very high in the margin of the nodule (172.22±45.66/mm²), moderate in healthy bowel tissue (111.48±48.57/mm²), and very low in the core of the nodule (7.31±4.9/mm²); p = .01. CONCLUSION: Both glandular and stromal cells within the rectosigmoid endometriosis nodule express estrogen and progesterone receptors. Higher intensity of expression of estrogen receptors occurs in glandular cells. The density of nerve fibers is extremely high at the nodule margin and very low in the center of the nodule.

In Vivo Confocal Microscopy of the Corneal Sub-Basal Nerve plexus in Medically Controlled Glaucoma.

The present study investigated the corneal sub-basal nerve plexus (SNP) modifications in glaucoma. Ninety-five glaucomatous patients were enrolled and divided into Group 1 and 2, preserved and preservative-free mono-therapy (30 and 28 patients), and Group 3, multi-therapy (37). Thirty patients with dry eye disease (DED) and 32 healthy subjects (HC) served as controls. In vivo confocal microscopy evaluated the nerve fibers density (CNFD), length (CNFL), thickness (CNFT), branching density (CNBD), and dendritic cell density (DCD). CNFD, CNFL, and CNBD were reduced in Group 3 and DED compared to HC (p < 0.05). CNFL was reduced in Group 3 compared to Group 2 (p < 0.05), and in Group 1 compared to HC (p < 0.001). CNFD, CNBD, and CNFT did not differ between glaucomatous groups. DCD was higher in Group 3 and DED compared to HC and Group 2 (p < 0.01). Group 3 showed worse ocular surface disease index (OSDI) scores compared to Group 1, 2, and HC (p < 0.05). CNFL and DCD correlated with OSDI score in Group 3 (r = −0.658, p < 0.001; r = 0.699, p = 0.002). Medical therapy for glaucoma harms the corneal nerves, especially in multi-therapy regimens. Given the relations with the OSDI score, SNP changes seem features of glaucoma therapy-related OSD and negatively affects the patient's quality of life.

Down-Regulation of Double C2 Domain Alpha Promotes the Formation of Hyperplastic Nerve Fibers in Aganglionic Segments of Hirschsprung's Disease.

Hirschsprung's disease (HSCR) is a common developmental anomaly of the gastrointestinal tract in children. The most significant characteristics of aganglionic segments in HSCR are hyperplastic extrinsic nerve fibers and the absence of endogenous ganglion plexus. Double C2 domain alpha (DOC2A) is mainly located in the nucleus and is involved in Ca2+-dependent neurotransmitter release. The loss function of DOC2A influences postsynaptic protein synthesis, dendrite morphology, postsynaptic receptor density and synaptic plasticity. It is still unknown why hyperplastic extrinsic nerve fibers grow into aganglionic segments in HSCR. We detected the expression of DOC2A in HSCR aganglionic segment colons and established three DOC2A-knockdown models in the Neuro-2a cell line, neural spheres and zebrafish separately. First, we detected the protein and mRNA expression of DOC2A and found that DOC2A was negatively correlated with AChE+ grades. Second, in the Neuro-2a cell lines, we found that the amount of neurite outgrowth and mean area per cell were significantly increased, which suggested that the inhibition of DOC2A promotes nerve fiber formation and the neuron's polarity. In the neural spheres, we found that the DOC2A knockdown was manifested by a more obvious connection of nerve fibers in neural spheres. Then, we knocked down Doc2a in zebrafish and found that the down-regulation of Doc2a accelerates the formation of hyperplastic nerve fibers in aganglionic segments in zebrafish. Finally, we detected the expression of MUNC13-2 (UNC13B), which was obviously up-regulated in Grade3/4 (lower DOC2A expression) compared with Grade1/2 (higher DOC2A expression) in the circular muscle layer and longitudinal muscle layer. The expression of UNC13B was up-regulated with the knocking down of DOC2A, and there were protein interactions between DOC2A and UNC13B. The down-regulation of DOC2A may be an important factor leading to hyperplastic nerve fibers in aganglionic segments of HSCR. UNC13B seems to be a downstream molecule to DOC2A, which may participate in the spasm of aganglionic segments of HSCR patient colons.

Changes in TRPV1 Expression as Well as Substance P and Vasoactive Intestinal Peptide Levels Are Associated with Recurrence of Pterygium.

Pterygium, a disease of the ocular surface, is characterized by the proliferation and invasion of fibrovascular tissue. Chronic inflammation contributes to pterygium occurrence. Sensory neuropeptides of TRPV1-positive nerve fibers are involved in inflammation and corneal wound healing. The possible association between TRPV1 in nerve fibers and neuropeptides such as Substance P (SP) and Vasoactive Intestinal Peptide (VIP) in the recurrence of pterygium has not been examined before. The pterygia from 64 patients were used to determine changes in SP and VIP levels using 10 min acetic-acid extraction that yielded mainly neuronal peptides. There was a sufficient amount of pterygium tissues from the 35 patients for further immunohistochemical analysis of TRPV1 and S100, which is a glial marker to visualize nerve fibers. SP and VIP levels increased markedly in cases with primary and secondary recurrences, and there was a close correlation between SP and VIP levels. TRPV1 expression increased in the epithelium, while stromal expression decreased in recurrences. Nerve fibers were demonstrated mainly in the stroma, and serial sections confirmed the localization of TRPV1 with the nerve fibers. These results together with previous findings demonstrated that the increased epithelial expression of TRPV1 in recurrent pterygia might be involved in the pathogenesis, and the inhibition of epithelial TRPV1 activity may prevent recurrence.

[Nerve fiber structure after different types of corneal transplantation]. / Struktura nervnykh volokon posle razlichnykh variantov peresadki rogovitsy.

This review presents basic information about the state of corneal nerve fibers and Langerhans cells before and after keratoplasty. Keratoplasty is a common corneal surgery that carries a risk of graft rejection. The state of corneal nerve fibers can vary after different types of keratoplasty. Corneal confocal microscopy allows in vivo evaluation of the cornea, which can help assess the condition of corneal nerve fibers, as well as reveal the presence of Langerhans cells. Further research in this direction would contribute to identifying the relationship between the state of corneal nerve fibers, the presence of Langerhans cells, and graft rejection.

Migrating and Nerve Fibers-Associated Eosinophilic Granule Cells in the Olfactory Organ of Catfish (Clarias garpienius): Light and Electron Microscopic Evidence.

Piscine mast cells or eosinophilic granule cells (EGCs) of fish are equivalent to the mammalian mast cells. Recently, a better understanding of EGCs functions is allowed because of the growing interest in fish models. Herein, we present a trial to furnish data regarding the distribution of the EGCs in the fish olfactory organ, an issue that has not been reported so far. Regarding their distribution, two kinds of EGCs had been identified. An intra-epithelial one was detected in the olfactory epithelium lining of the olfactory lamellae. The stromal one was identified in the connective tissue core of the olfactory lamellae and in the lamina propria underlying the olfactory epithelium. Some were detected in the capillary lumen. The cytoplasm of the EGCs reacted strongly with the MMP-9 antibody. Stimulating a migration perspective for the olfactory EGCs which was confirmed by their location in the blood capillaries. Several EGCs could be verified in close relation, some underneath the epineurium, with the nerve fiber. Mutually, this verifies the existence of intra-epithelial and stromal migrating EGCs in the catfish olfactory organ and their inclusion in the olfactory immune response. Additionally, this provides evidence for an immune­nervous interaction to influence both the immune reactions and the nervous scheme in catfish.