Evaluation of innervation in cleft affected oral mucosa

Orofacial clefts are one of the most common pathologies present at birth. The aim of the study was to evaluate the presence of PGP 9.5, substance P, VIP, CGRP, myelin and NFG in cleft affected mucosa of alveolar process, soft and hard palate, vomer and lip. Methods. Orofacial cleft affected mucosa tissue samples were obtained during surgical cleft correction from 21 children aged from 2 months to 9 years and 10 months. Prepared tissue sections were stained by immunohistochemistry for PGP 9.5, substance P, VIP, CGRP, myelin and NGF. The intensity of staining was graded semiquantitatively. Results. Mostly moderate number and numerous PGP 9.5, substance P, VIP, CGRP, myelin and NGF-containing nerve fibres and nerve fibre bundles and CGRP and NGF positive keratinocytes were detected. The most immunoreactive for PGP 9.5, myelin and NGF were nerve fibres, nerve fibre bundles and keratinocytes in lip mucosa tissue samples. Typically, PGP 9.5-containing nerve fibres were detected in subepithelium close to basal lamina, near blood vessels; thin PGP 9.5 positive nerve fibres were also observed between keratinocytes. Immunoreactivity of CGRP was higher than of substance P in nerve fibres and nerve fibre bundles. Statistically significant positive correlation was observed between all markers in subepithelium of all tissue samples. Conclusions. The proved statistically significant strong inter-correlation and the number of general neuropeptide-containing innervation (PGP 9.5), sensory nerves (CGRP and substance P), and parasympathetic nerves (VIP) is similar in orofacial cleft affected oral mucosa to such described in scientific literature healthy oral mucosa, except the alveolar process covering mucosa where the above innervation varies. Very strong and strong statistically significant positive correlations between the number of PGP 9.5, substance P, CGRP and VIP positive structures on the one hand, and NGF and myelin, on the other hand, indicate a connection between quality markers and common neuropeptide-containing, sensory and parasympathetic innervation in cleft affected oral tissue. The number of PGP 9.5, NGF and myelin immunoreactive neuronal structures in lip mucosa is higher than in the alveolar process, soft and hard palate and vomer mucosa, suggesting the significance of qualitative common innervation in this organ even in the cleft affected case.

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THE PROGNOSTIC VALUE OF PD-L1 EXPRESSION IN TUMOR AND IMMUNE CELLS IN SQUAMOUS CELL CARCINOMA OF THE ORAL MUCOSA

Problems in oncology ◽

10.37469/0507-3758-2017-63-5-759-765 ◽

2017 ◽

Vol 63 (5) ◽

pp. 759-765

Author(s):

Svetlana Kutukova ◽

Natalya Belyak ◽

Grigoriy Raskin ◽

Marina Mukhina ◽

Georgiy Manikhas ◽

...

Keyword(s):

Oral Mucosa ◽

Malignant Tumor ◽

Immune Cells ◽

Prognostic Value ◽

Hard Palate ◽

Malignant Tumors ◽

Small Cell ◽

Alveolar Process ◽

Small Cell Lung ◽

Lower Jaw

The most frequent of malignant tumor cites of the oral mucosa are tongue - 55 %, mucosa of the cheek - 12 %, the fundus of the oral cavity - 10 %, the alveolar process of the upper jaw and the hard palate - 9 %, the alveolar process of the lower jaw - 6 %, the soft palate - 2 %. Malignant tumor cells carry PD-L1 ligands on their surface and its expression level is often correlated with an unfavorable prognosis in particular for such tumors as melanoma, kidney cancer and non-small cell lung cancer. It is relevant to evaluate the correlation between overexpression of PD-L1 and overall survival in patients with malignant tumors of the oral mucosa.

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Evaluation of TGF-β1 and EGFR in Cleft Affected Lip Mucosa

Acta medica Lituanica ◽

10.15388/amed.2021.28.1.14 ◽

2021 ◽

Vol 28 (1) ◽

pp. 14

Author(s):

Olga Rimdenoka ◽

Māra Pilmane

Keyword(s):

Epithelial Cells ◽

Lamina Propria ◽

Oral Mucosa ◽

Rank Correlation ◽

Control Group ◽

Orofacial Cleft ◽

Tissue Samples ◽

Moderate Number ◽

Healthy Mucosa ◽

Tgf Β1

Background. The morphopathogenesis of orofacial cleft development is only partly understood; therefore, it is important to identify factors, which possibly could be involved in it. The aim of the study was to evaluate the distribution of TGF-β1 and EGFR-containing cells in cleft affected lip mucosa.Materials and Methods. The study group included lip mucosa tissue samples from 14 patients with orofacial cleft. The control group contained 11 healthy oral mucosa tissue samples. The tissue sections were stained by immunohistochemistry for TGF-β1 and EGFR. The expression of positive structures was graded semiquantitatively. IBM SPSS 26.0 was used for statistical analysis, Spearman`s rank correlation and Mann-Whitney U tests were performed.Results. Mostly few to moderate number (+/++) of TGF-β1-containing cells was found in epithelium, also the same number of fibroblasts and macrophages was seen in the lamina propria of cleft affected lip mucosa. Meanwhile, healthy oral mucosa on average demonstrated a moderate number (++) of TGF-β1-containing epithelial cells, fibroblasts, and macrophages. A variable, mostly indistinct number of EGFR-containing cells was seen in the epithelium of cleft affected lip mucosa, meanwhile, mostly no (0) EGFR positive cells were found in the epithelium of healthy mucosa. Statistically significantly less TGF-β1-containing cells were found in the epithelium of cleft affected lip mucosa than in the healthy mucosa (U=33.000; p=0.015). Also, the lamina propria of cleft affected lip mucosa showed statistically significantly less TGF-β1 immunoreactive fibroblasts and macrophages than the healthy mucosa (U=28.500; p=0.006).Conclusions. The decreased number of TGF-β1-containing epithelial cells, fibroblasts and macrophages in cleft affected lip mucosa proves the role of problematic tissue remodelation in the cleft pathogenesis. The distribution of EGFR in cleft affected and healthy mucosa is similar and possibly does not play a role in the cleft development of humans.

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Early Detection of Diabetic Peripheral Neuropathy: A Focus on Small Nerve Fibres

Diagnostics ◽

10.3390/diagnostics11020165 ◽

2021 ◽

Vol 11 (2) ◽

pp. 165

Author(s):

Jamie Burgess ◽

Bernhard Frank ◽

Andrew Marshall ◽

Rashaad S. Khalil ◽

Georgios Ponirakis ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Nerve Fibre ◽

Diabetic Peripheral Neuropathy ◽

Point Of Care ◽

Unmet Need ◽

Screening Tools ◽

Nerve Fibres ◽

Diagnostic Laboratory ◽

Corneal Confocal Microscopy ◽

Small Nerve

Diabetic peripheral neuropathy (DPN) is the most common complication of both type 1 and 2 diabetes. As a result, neuropathic pain, diabetic foot ulcers and lower-limb amputations impact drastically on quality of life, contributing to the individual, societal, financial and healthcare burden of diabetes. DPN is diagnosed at a late, often pre-ulcerative stage due to a lack of early systematic screening and the endorsement of monofilament testing which identifies advanced neuropathy only. Compared to the success of the diabetic eye and kidney screening programmes there is clearly an unmet need for an objective reliable biomarker for the detection of early DPN. This article critically appraises research and clinical methods for the diagnosis or screening of early DPN. In brief, functional measures are subjective and are difficult to implement due to technical complexity. Moreover, skin biopsy is invasive, expensive and lacks diagnostic laboratory capacity. Indeed, point-of-care nerve conduction tests are convenient and easy to implement however questions are raised regarding their suitability for use in screening due to the lack of small nerve fibre evaluation. Corneal confocal microscopy (CCM) is a rapid, non-invasive, and reproducible technique to quantify small nerve fibre damage and repair which can be conducted alongside retinopathy screening. CCM identifies early sub-clinical DPN, predicts the development and allows staging of DPN severity. Automated quantification of CCM with AI has enabled enhanced unbiased quantification of small nerve fibres and potentially early diagnosis of DPN. Improved screening tools will prevent and reduce the burden of foot ulceration and amputations with the primary aim of reducing the prevalence of this common microvascular complication.

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The nature of the substance P-containing nerve fibres in taste papillae of the rat tongue

Neuroscience ◽

10.1016/0306-4522(82)90236-6 ◽

1982 ◽

Vol 7 (12) ◽

pp. 3137-3151 ◽

Cited By ~ 96

Author(s):

J.I. Nagy ◽

M. Goedert ◽

S.P. Hunt ◽

A. Bond

Keyword(s):

Substance P ◽

Nerve Fibres ◽

Rat Tongue

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The ectopic newly-formed nerve fibres which repopulate the long-time denervated and atrophic chick skeletal muscle

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x1968000300001 ◽

1968 ◽

Vol 26 (3) ◽

pp. 187-194 ◽

Cited By ~ 3

Author(s):

Eros Abrantes Erhart ◽

Cecil José Rezze ◽

Walter Biazotto

Keyword(s):

Skeletal Muscle ◽

Electrical Stimulation ◽

Nerve Fibre ◽

Nerve Trunk ◽

Direct Electrical Stimulation ◽

Nerve Fibres ◽

Motor Endplates ◽

Proximal Stump ◽

Long Time ◽

Contralateral Muscle

1. The whole biventer cervicis muscles of the chick, being innervated by a branch of the dorsal ramus of C, presents structural Deculiarities which recommend it as good skeletal muscle for embryological, anatomical, physiological and pharmacological neuro-muscular investigations. 2. The nerve trunk responsible for the innervation of the distal belly runs completely included within the intermediate tendon; therefore, a tendon transection determines complete denervation and nerve fibre degeneration of the distal belly of the muscle. 3. Long-time experimentally denervated distal bellies (from three up to twelve months) are repopulated by ectopic nerve fibres which must have arisen from a source other than the proximal stump, neighbour nerves or nervi-vasorum. 4. Motor endplates appear in these long-time (eight or more months) denervated biventer cervicis distal bellies. 5. Although atrophic-looking such muscle bellies responded to indirect and to direct electrical stimulation — 1.5 V — by contraction. 6. The long-time denervated distal bellies of the biventer cervicis muscle of the chick, when properly reoperated by cross-grafting suture with the normal contralateral muscle, lost their atrophic appearance and showed to be successfully recovered in about thirty days.

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Aberrant Nerve Fibres in Human Development

Development ◽

10.1242/dev.8.2.119 ◽

1960 ◽

Vol 8 (2) ◽

pp. 119-129

Author(s):

J. D. Boyd ◽

A. F. W. Hughes

Keyword(s):

Nervous System ◽

Human Development ◽

Nerve Fibre ◽

Early Years ◽

Developmental Studies ◽

Nerve Fibres ◽

Ground Plan ◽

Technical Developments ◽

Previous Decade ◽

Ramón Y Cajal

In the early years of this century debate concerning the development of nerve fibres became more intense. During the previous decade, following the developmental studies of His (1883, 1886) and the early embryological studies of Ramon y Cajal (1890), the neurone theory as proclaimed by Waldeyer in 1891 seemed assured of victory; but when, with Apáthy and Bethe, new technical developments diverted attention from the whole neurone to its apparent constituents, the neurofibrillae, the simple concept of the outgrowth of the nerve fibre became enmeshed in complexity. Methods for their impregnation with silver were soon elaborated (Bielschowsky, 1904; Ramon y Cajal, 1903), and Held (1907) affirmed that a network of neurofibrillae preceded the appearance of the definitive nerve process. This claim became associated with the much older views of Hensen (1864, 1876) that protoplasmic strands were the forerunners of the nerve fibres and constituted a ground plan for the later development of the peripheral nervous system.

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Neutral endopeptidase modulates substance P-induced vasodilation in vivo

Journal of Applied Physiology ◽

10.1152/jappl.1995.78.2.562 ◽

1995 ◽

Vol 78 (2) ◽

pp. 562-568 ◽

Cited By ~ 9

Author(s):

X. P. Gao ◽

I. Rubinstein

Keyword(s):

Substance P ◽

Oral Mucosa ◽

Intravital Microscopy ◽

Neutral Endopeptidase ◽

Cheek Pouch ◽

Induced Responses ◽

Hamster Cheek Pouch ◽

Arteriolar Diameter ◽

Significant Concentration

The purpose of this study was to investigate whether neutral endopeptidase (NEP; EC 3.4.24.11) modulates substance P-induced vasodilation in the oral mucosa in vivo. Using intravital microscopy, we measured the diameter of second-order arterioles (44–70 microns) in the hamster cheek pouch during suffusion of capsaicin and substance P. We found that capsaicin (0.1 and 10.0 nM) induced significant concentration-dependent vasodilations (13 +/- 4 and 39 +/- 7% increase from baseline, respectively; P < 0.05) that were significantly potentiated by phosphoramidon (10.0 nM), a selective NEP inhibitor (35 +/- 15 and 61 +/- 12% increase from baseline, respectively; P < 0.05). Substance P (0.1 and 10.0 nM) also induced significant concentration-dependent vasodilations (7 +/- 3 and 25 +/- 8% increase from baseline, respectively; P < 0.05) that were mediated by the COOH-terminal of the molecule. Substance P-induced responses were significantly potentiated by phosphoramidon (34 +/- 9 and 53 +/- 10% increase from baseline, respectively; P < 0.05) and thiorphan (10.0 microM), a selective NEP inhibitor (44 +/- 11 and 53 +/- 10% increase from baseline, respectively; P < 0.05). Substance P-(1–9) had no significant effects on arteriolar diameter. Suffusion of captopril, leupeptin, Bestatin, and DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid together had no significant effects on substance P-induced vasodilation. Phosphoramidon did not potentiate nitroglycerin-induced vasodilation. These data indicate that NEP modulates substance P-induced vasodilation in the hamster cheek pouch in vivo. We suggest that any decrease in tissue NEP activity may amplify neurogenic vasodilation in the oral mucosa.

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Age-related changes in substance P-immunoreactive nerve structures of the rat recto-anal region

Open Medicine ◽

10.2478/s11536-009-0098-2 ◽

2010 ◽

Vol 5 (3) ◽

pp. 358-364

Author(s):

Nikolai Lazarov ◽

Dimitar Itzev ◽

Kamen Usunoff ◽

Negrin Negrev ◽

Radomir Radomirov

Keyword(s):

Substance P ◽

Anal Sphincter ◽

Internal Anal Sphincter ◽

Circular Muscle ◽

Muscle Layer ◽

Nerve Fibres ◽

Anal Region ◽

Age Related ◽

Old Rats ◽

Age Related Changes

AbstractThe recto-anal region is innervated by extrinsic and intrinsic nerves and a number of neuropeptides including substance P (SP) have been suggested to participate in the regulation of intestinal movements. We examined the age-related changes in the distribution of SP-immunoreactive nerve structures in the distal part of the rat large intestine. Using immunohistochemistry, the presence of SP was studied in fresh tissues from Wistar rats at different ages taken at three sampling sites, the distal rectum, anal canal and internal anal sphincter. In the 15-day old rats the myenteric plexus of the distal rectum and anal canal was well outlined by numerous SP-immunoreactive varicose nerve fibres encircling immunonegative perikarya. In the circular muscle layer, nerve fibres and small nerve bundles ran parallel to the muscle cells, while in the longitudinal muscle layer, only occasional nerve fibres were seen. At the level of the internal anal sphincter, no myenteric ganglia were present. Here, thin varicose fibers ran parallel to the smooth muscle cells. In the 3-month old rats, a larger number of intensely staining SP-immunoreactive nerve fibres were found and in the circular muscle layer, thicker nerve strands were observed. In the 26-month old rats, the density and staining intensity of SP-immunopositive nerve fibres in the myenteric plexus was lower than in the 3-month-old rats. Similar changes in the SP-immunostained fibres in the internal anal sphincter were observed. Degenerative alterations in SP-containing fibres during aging appear to play a role in ano-rectal motility and sphincter control.

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