A Case-Control study of the prevalence of neurological diseases in inflammatory bowel disease (IBD) / Um estudo de caso-controle da prevalência de doenças neurológicas na doença inflamatória intestinal (DII)

Neurological diseases are common in inflammatory bowel disease (IBD) patients, but their exact prevalence is unknown. Method We prospectively evaluated the presence of neurological disorders in 121 patients with IBD [51 with Crohn's disease (CD) and 70 with ulcerative colitis (UC)] and 50 controls (gastritis and dyspepsia) over 3 years. Results Our standard neurological evaluation (that included electrodiagnostic testing) revealed that CD patients were 7.4 times more likely to develop large-fiber neuropathy than controls (p = 0.045), 7.1 times more likely to develop any type of neuromuscular condition (p = 0.001) and 5.1 times more likely to develop autonomic complaints (p = 0.027). UC patients were 5 times more likely to develop large-fiber neuropathy (p = 0.027) and 3.1 times more likely to develop any type of neuromuscular condition (p = 0.015). Conclusion In summary, this is the first study to prospectively establish that both CD and UC patients are more prone to neuromuscular diseases than patients with gastritis and dyspepsia. .

Doenças neurológicas são comuns em pacientes com doença inflamatória intestinal (DII), mas sua prevalência exata é desconhecida. Métodos Nós estudamos prospectivamente a presença de distúrbios neurológicos em 121 pacientes com DII [51 com doença de Crohn (DC) e 70 com colite ulcerativa (RCU)] e 50 controles (gastrite e dispepsia) ao longo de 3 anos. Resultados A avaliação neurológica padronizada (que incluiu testes eletrodiagnósticos) demonstrou que pacientes com DC foram 7,4 vezes mais propensos a desenvolver neuropatias de fibras grossas do que os controles (p = 0,045), 7,1 vezes mais propensos a desenvolver qualquer tipo de condição neuromuscular (p = 0,001) e 5,1 vezes mais propensos a desenvolver queixas autonômicas (p = 0,027). Pacientes com RCU foram 5 vezes mais propensos de desenvolver neuropatia de fibras grossas (p = 0,027) e 3,1 vezes mais propensos a desenvolver qualquer tipo de condição neuromuscular (p = 0,015). Conclusão Em resumo, este é o primeiro estudo prospectivo a estabelecer que os pacientes tanto com DC quanto de RCU são mais propensos a doenças neuromusculares do que os pacientes com gastrite e dispepsia. .

Histochemical study of the definitive erythropoietic foci in the chicken yolk sac.

It is well known that avian yolk sac is involved in both primitive and definitive erythropoiesis during embryonic development. Definitive erythropoiesis is first detected at about 4-5 days incubation and its maximum activity is reached between day 10 and 15 of incubation, ending between days 18 and 20 of incubation. We confirmed the definitive erythropoietic foci in the chicken yolk sac throughout the 5th to 19th day of incubation by histochemical light and electron microscopy. The definitive erythropoietic foci were observed in the yolk sac endodermal layer from day 5 until day 19, just before hatching. Ultrastructurally, definitive erythropoietic foci were observed extravascularly in the yolk sac endodermal cell layer in direct contact with the vitellolysis zone. These findings provide a basis for clarifying definitive erythropoiesis in vertebrates.

Impact of size at birth on the microvasculature: the Avon Longitudinal Study of Parents and Children.

BACKGROUND: The impact of early life factors on the microvasculature is relatively unknown. OBJECTIVES: We hypothesized that small birth size may be associated with structural variations in the retinal vasculature in children. METHODS: The Avon Longitudinal Study of Parents and Children followed a cohort of children born in 1991-1992 from birth. The current study included the first 263 children who were systematically screened in the year-12 follow-up. Complete data were available for 166 children with a gestation of > or = 37 weeks. Retinal circulatory measures were evaluated, including retinal microvascular tortuosity and bifurcation optimality deviance, an indicator of abnormal endothelial function. RESULTS: Optimality deviance and retinal tortuosity were higher among those with lower birth weight. Linear regression modeling was used to assess the association of retinal microvascular measures with birth weight. The standardized beta coefficient between optimality deviance and birth weight was -.182 adjusted for gender and age in weeks; additional adjustment for systolic blood pressure and heart rate had little impact on the beta coefficient. A similar association was observed for retinal tortuosity. CONCLUSION: The findings of this study suggest that early life factors may have an important impact on retinal vascular structure, possibly through an adverse effect on endothelial function.

N-acetylchitooligosaccharide is a potent angiogenic inhibitor both in vivo and in vitro.

N-acetylchitooligosaccharide (N-acetyl-COs) was prepared by N-acetylation of chitooligosaccharide (COs). In vitro study using human umbilical vein endothelial cells (HUVECs) revealed that both N-acetyl-COs and COs inhibited the proliferation of HUVECs by inducing apoptosis. Treatment of HUVECs by N-acetyl-COs resulted in a significant reduction of density of the migration cells and repressed tubulogenesis process. The antiangiogenic effects of the oligosaccharides were further evaluated using in vivo zebrafish angiogenesis model, and the results showed that both oligosaccharides inhibited the growth of subintestinal vessels (SIV) of zebrafish embryos in a dose-dependent manner, as observed by endogenous alkaline phosphatase (EAP) staining assay. In contrast, no cytotoxicity was found when treating the NIH3T3 and several other cancer cells with the oligosaccharides. Our results also confirmed the antiangiogenic activity of N-acetyl-COs was significantly stronger than the parent oligosaccharide, COs.

Angiogenic effect of intercellular adhesion molecule-1.

UNLABELLED: In order to investigate the angiogenic effect of intercellular adhesion molecule-1 (ICAM-1), two parts of experiment were performed. Chick embryo chorioallantoic membrane (CAM) assay was used for in vivo angiogenic research. The chick embryos were divided into 4 groups: ICAM-1 group (divided into 3 subgroups, I, II and III) for screening the angiogenic effect of ICAM-1 by adding different concentrations of ICAM-1 (0.1, 0.2 and 0.3 microg/microL) 5 microL into the chick embryo CAMs on the day 10 after incubation for every subgroup; Anti-ICAM-1 group A (divided into 2 subgroups, I and II) by adding different concentrations of Anti-ICAM-1 (1:100, 1:50) 5 microL into the chick embryo CAMs on the day 10 after incubation for every subgroup to evaluate the effect of ICAM-1 on the survival of microvessels through observing whether Anti-ICAM-1 could induce involution of the microvessels on CAMs; Anti-ICAM-1 group B (divided into 2 subgroups, I and II) by adding different concentrations of Anti-ICAM-1 (1:100, 1:50) 5 microL into the chick embryo CAMs on the day 6 after incubation for every subgroup to evaluate whether ICAM-1 involved in embryonic angiogenesis through observing the growth of microvessels on CAMs; CONTROL GROUP: ICAM-1 or Anti-ICAM-1 was substituted by PBS 5 muL on the day 10 or day 6 after incubation. Three days later, the CAMs were photographed in vivo, excised, sectioned and the number of microvessels was counted. In ICAM-1 group, there was increased number of microvessels arranged radially with "spoked-wheel" pattern around the gelatin sponges. The new microvessels growing perpendicularly to gelatin sponges were observed. The number of the microvessels growing in the CAM mesenchymes around the sponges in 3 subgroups was higher than that in control group (P<0.01), however, there was no significant difference among the 3 subgroups (P>0.05). In anti-ICAM-1 group A, the radially arranged microvessels were very unclear around the sponges contrast to that of ICAM-1 group. Few new microvessels were detected in the center of the sponges. The number of the microvessels growing in the CAM mesenchymes around the sponges in subgroup II was lower than that in control group (P<0.01). There was no significant difference in the number of the microvessels around the sponges between subgroup I and control group (P>0.05). In anti-ICAM-1 group B, the radially arranged microvessels were very unclear around the sponges contrast to that of control group. New microvessels were very scarce in the center of the sponges. The number of the microvessels growing in the CAM mesenchymes around the sponges in the 2 subgroups were less than that in control group (P<0.01), and there was significant difference between the 2 subgroups (P<0.05). It was suggested that ICAM-1 could induce angiogenesis and support the survival of microvessels, and ICAM-1 was involved in embryonic angiogenesis.

Developmental basis of vascular smooth muscle diversity.

The origins of vascular smooth muscle are far more diverse than previously thought. Lineage mapping studies show that the segmental organization of early vertebrate embryos leaves footprints on the adult vascular system in the form of a mosaic pattern of different smooth muscle types. Moreover, evolutionarily conserved tissue forming pathways produce vascular smooth muscle from a variety of unanticipated sources. A closer look at the diversity of smooth muscle origins in vascular development provides new perspectives about how blood vessels differ from one another and why they respond in disparate ways to common risk factors associated with vascular disease. The origins of vascular smooth muscle are far more diverse than previously thought. A closer look at the diversity of smooth muscle origins in vascular development provides new perspectives about how blood vessels differ from one another and why they respond in disparate ways to common risk factors associated with vascular disease.

An intimate interplay between precocious, migrating pericytes and endothelial cells governs human fetal brain angiogenesis.

In order to better understand the process of angiogenesis in the developing human brain, we have examined the spatial relationship and relative contributions of endothelial cells and pericytes, the two primary cell types involved in vessel growth, together with their relation with the vascular basement membrane. Pericytes were immunolocalized through use of the specific markers nerve/glial antigen 2 (NG2) proteoglycan, endosialin (CD248) and the platelet-derived growth factor receptor beta (PDGFR-beta), while endothelial cells were identified by the pan-endothelial marker CD31 and the blood brain barrier (BBB)-specific markers claudin-5 and glucose transporter isoform 1 (GLUT-1). The quantitative analysis demonstrates that microvessels of the fetal human telencephalon are characterized by a continuous layer of activated/angiogenic NG2 pericytes, which tightly invest endothelial cells and participate in the earliest stages of vessel growth. Immunolabelling with anti-active matrix metalloproteinase-2 (aMMP-2) and anti-collagen type IV antibodies revealed that aMMP-2 producing endothelial cells and pericytes are both associated with the vascular basement membrane during vessel sprouting. Detailed localization of the two vascular cell types during angiogenesis suggests that growing microvessels of the human telencephalon are formed by a pericyte-driven angiogenic process in which the endothelial cells are preceded and guided by migrating pericytes during organization of the growing vessel wall.

Transient expression of endothelins in the amoeboid microglial cells in the developing rat brain.

Amoeboid microglial cells (AMC) which transiently exist in the corpus callosum in the postnatal rat brain expressed endothelins (ETs), specifically endothelin-1 (ET-1) and ET3 as revealed by real time RT-PCR. ET immunoreactive AMC occurred in large numbers at birth, but were progressively reduced with age and were undetected in 14 days. In rats subjected to hypoxia exposure, ET immunoexpression in AMC was reduced but the incidence of apoptotic cells was not increased when compared with the control suggesting that this was due to its downregulation that may help regulate the constriction of blood vessels bearing ET-A receptor. AMC were endowed ET-B receptor indicating that ET released by the cells may also act via an autocrine manner. In microglia activated by lipopolysaccharide (LPS), ET-1 mNA expression coupled with that of monocyte chemoattractant protein (MCP-1) and stromal derived factor-1 (SDF-1) was markedly increased; ET-3 mRNA, however, remained unaffected. AMC exposed to oxygen glucose deprivation (OGD) in vitro resulted in increase in both ET-1 and ET-3 mRNA expression. It is suggested that the downregulated ETs expression in vivo of AMC subjected to hypoxia as opposed to its upregulated expression in vitro may be due to the complexity of the brain tissue. Furthermore, the differential ET-1 and ET-3 mRNA expression in LPS and OGD treatments may be due to different signaling pathways independently regulating the two isoforms. The present novel finding has added microglia as a new cellular source of ET that may take part in multiple functions including regulating vascular constriction and chemokines release.

Human microvascular endothelial cells from different fetal organs demonstrate organ-specific CAM expression.

In this work, we isolated and produced long-term cultures of human fetal endothelial cells (fECs) deriving from different organs of the same 12-week-old embryos. Highly pure endothelium cultures were obtained from specimens of brain, heart, lung, liver, aorta and kidney by using magnetic microspheres coated with CD31 or CD34 specific endothelial antibodies. The endothelial nature of these cells was confirmed by the presence of von Willebrand Factor (vWf), Flk-1/VEGFR2 and CD31. The fECs cultures showed organ-specific differences as regards to the morphological appearance, the growth rate and the expression of cellular adhesion molecules (CAMs) before or after stimulation by the inflammatory cytokines IL-1beta and TNF-alpha. For instance, TNF-alpha showed a specific effect on fetal heart ECs by stimulating E-selectin expression. Our findings indicate that fECs may represent an innovative tool to study differences among ECs of different vascular districts of the same individual, thus increasing the possibility to compare many pathological aspects of human adult and fetal microvasculature.

Involvement of metalloprotease-2 in the development of human brain microvessels.

The involvement of the metalloprotease-2 (MMP-2) in vessel development was investigated in the human telencephalon by double immunoreactions with antibodies to the enzyme, latent (proMMP-2) and active (aMMP-2) forms, and an antibody against collagen type IV, a constitutive component of the extracellular matrix (ECM) of the vessel basal lamina. MMP-2 is expressed in both 12- and 18-week telencephalic vessels, the proenzyme being mainly localised in endothelial cells and the active form prevailing in alpha-actin-reactive periendothelial cells identified as pericytes. Endothelial cells intensely positive for aMMP-2 were revealed in some microvessels and appeared locally associated with discontinuities of the collagen basal lamina. No detectable expression of MMP-2 was observed in perivascular glial processes revealed by vimentin/glial fibrillary acidic protein immunostainings. Double immunoreactions performed to further investigate telencephalon angiogenesis have demonstrated that both the endothelial cells and pericytes strongly express vascular endothelial growth factor (VEGF). Taken together, the results indicate that MMP-2 is largely involved in human brain angiogenesis and suggest that endothelial cells and pericytes tightly interplay in both angiogenesis mechanisms, by ECM proteolysis, and angiogenesis regulation, by local (autocrine/juxtacrine) VEGF action.

Watershed infarcts in the fetal and neonatal brainstem. An aetiology of central hypoventilation, dysphagia, Möibius syndrome and micrognathia.

Watershed zone infarcts of the human cerebral cortex at the overlapping junctions of the anterior and middle cerebral arterial territories are well known. Another watershed zone exists in the brainstem tegmentum, between the terminal perfusion zones of the paramedian penetrating and long circumferential arteries, which are paired segmental vessels arising from the basilar artery. The vertebrobasilar circulation achieves its mature configuration and caudorostral flow by 9 weeks gestation. Systemic hypotension and other conditions of reduced basilar perfusion in the fetus, either early or late in gestation, may result in symmetrical longitudinal columns of infarction in the midbrain and tegmentum of the pons and medulla oblongata and laminar necrosis of the midbrain tectum. Within this zone are cranial nerve nuclei III-XII, the nucleus and tractus solitarius or central pneumotaxic center, as well as the nucleus ambiguus and other somatic motor nuclei that subserve muscles of swallowing, mastication and tongue movement. Watershed infarcts in the human fetal and neonatal brainstem are clinically expressed as multiple cranial neuropathies, failure of central respiratory drive and apnea, dysphagia and aspiration, Möbius syndrome and Pierre Robin sequence. MRI is sometimes helpful, but most of the involved neuroanatomical structures are beneath the resolution of present imaging techniques, and the diagnosis during life depends upon clinical neurological examination of the neonate, sometimes supported by evoked potential studies. Postmortem examination confirms the diagnosis and dates the lesions, but also contributes to better understand transient or persistent vascular insufficiencies in the fetal and neonatal brainstem.

Lung microvascular adaptation in infants with chronic lung disease.

Microvascular development is critical for normal lung maturation. The aims of this study were (1) to quantitatively and qualitatively assess lung microvascular growth in the human fetus, from 22 to 40 weeks' gestation, and (2) to compare development in these infants to those with mild, moderate and severe chronic lung disease (CLD). Using 1- and 4-microm thick sections and electron microscopy, lungs were morphometrically assessed for surface density of distal air spaces; volume density of parenchymal vessels having an air-blood barrier (ABB); percent of distal air space wall having an ABB, and capillary loading, defined as ABB/mm2 of epithelial surface area. The percent of vessels with ABB increased in controls during development in parallel with increasing lung parenchyma. Infants with severe CLD had fewer ABBs and less capillary loading than controls up to 34 weeks' post-conceptional age (PCA), but by 36-40 weeks, showed catch-up growth. Microvasculature vessel diameter, septal thickness, and air sac diameter at 36-40 weeks' PCA were increased with severe CLD, and vessels were more distant from the air surface. We conclude that infants with severe CLD have both stunted secondary septation and microvascular development, but over time, the primary septal wall adapts by thinning and increasing the number of ABBs, thereby taking on the function of secondary septa.

Recombinant human erythropoietin induces intussusceptive microvascular growth in vivo.

The role of erythropoietin (Epo) in angiogenesis has not been completely clarified. Epo induces endothelial cell proliferation and migration and stimulates angiogenesis on rat aortic rings in vitro and in vivo in the chick embryo chorioallantoic membrane (CAM) assay. The aim of the present study was to evaluate the ultrastructural aspects of angiogenesis in the CAM vasculature after recombinant human Epo (rHuEpo) exposure. The results demonstrated that after rHuEpo stimulation, the generation of new blood vessels occurred more frequently following an intussusceptive microvascular growth (IMG) mechanism. We have performed our experiments between days 8 and 12 of incubation, that is, when in the normal condition the capillary network expands mainly by IMG, and because it is generally accepted that implants made from days 8 to 10 are strongly angiogenic. This response is peculiar of rHuEpo, because it is abolished when an Epo-blocking antibody was coadministered with Epo.

Effects of 6-aminonicotinamide gliotoxin on blood-brain barrier differentiation in the chick embryo cerebellum.

The hypothesis of astroglial cell involvement in prenatal setting up of the blood-brain barrier (BBB) has been examined by producing glial degeneration in cerebellum of chicken embryos submitted to the action of gliotoxin 6-aminonicotinamide (6-AN), which was applied onto the embryo chorioallantoic membrane during both early and late embryonic development. The effects of 6-AN on the cerebellum astroglial cells and microvessels were analysed under the light microscope by immunostaining for 3CB2 (chick-specific glial marker) and HT7 (chick-specific marker of BBB-provided brain endothelia), under the electron microscope, as well as by the vascular permeability tracer horseradish peroxidase. The results, showing good suitability of the 6-AN model also when applied in early embryonic development, demonstrated a correlation between perivascular glia depletion and endothelial barrier impairment and suggested that astroglia play a role in the BBB prenatal differentiation.

Microvascular architecture of the fetal cotyledons in water buffaloes (Bubalus bubalis) during different stages of pregnancy.

To elucidate the morphological background of physiological differences between bovine and buffalo gestation forty-two placentae ranging from the 3rd to 10th month of pregnancy were used to study the microvascular architecture of the fetal cotyledons in the buffalo. The tissues were prepared for light and scanning electron microscopy by paraformaldehyde fixation and corrosion casting of the fetal cotyledonary vascular system. Histology and vascular casts revealed the buffalo fetal cotyledons to consist of a series of conical villous trees changing from a wide to slender shape during pregnancy, and with a base strictly facing the fetal side. The branches of these trees, intermediate and terminal villi, projected radially from the stem, thus representing a rough type of villous tree. A second type of tree lacked these branches and was therefore termed smooth villus. The rough type was most prevalent, and the intermediate and terminal villi showed capillary complexes arranged in stories by the 4th to 5th month of gestation. The stories became broader and denser with the progress of pregnancy (6th to 7th month of gestation), due to extensive growth of new capillaries and simultaneous development of convolutions causing the vascular ridges of the terminal villi to appear bushy. Near term (9th to 10th month) the capillary system became very dense, particularly at the margin of the vascular ridges, leaving only narrow spaces for the corresponding maternal septal tissue. In detail, at its base the trunk of each villous tree contained a single central stem artery which originated from the allantochorionic arterial system, and 1-3 parallel peripheral stem veins. When approaching the cone tip, these vessels branched into new stem arteries and veins, each giving rise to arterioles and venules according to the principle vascularization of the stem villus first, followed by intermediate and terminal villi. The capillary complex of the terminal villi consisted of arterial capillary limbs, capillary loops with sinusoidal dilatations and anastomoses, and venous capillary limbs. The latter converged into venules of terminal and intermediate villi which joined stem veins leading into allantochorionic veins. In conclusion, the fetal vasculature of the buffalo placentome was greatly increased from early pregnancy to near term. This was denoted by the general development of stem villous trees and an increase in the volume and density of the capillary system of the terminal villi, reflecting the increasing need of materno-fetal substance exchange in the buffalo placenta, particularly near term.

VEGF expression by ganglion cells in central retina before formation of the foveal depression in monkey retina: evidence of developmental hypoxia.

In macaque monkeys the foveal depression forms between fetal day (Fd) 105 and birth (Fd 172 of gestation). Before this, the incipient fovea is identified by a photoreceptor layer comprising cones almost exclusively, a multilayered ganglion cell layer (GCL), and a "domed" profile. Vessels are absent from the central retina until late in development, leading to the suggestion that the GCL in the incipient fovea may be transitorily hypoxic. Vascular endothelial growth factor (VEGF), expressed by both glial and neuronal cells and mediated by the hypoxia-inducible transcription factor (HIF)-1, is the principal factor involved in blood vessel growth in the retina. We examined VEGF expression in macaque retinas between Fd 85 and 4 months postnatal. Digoxygenin-labeled riboprobes were generated from a partial-length human cDNA polymerase chain reaction fragment, detected using fluorescence confocal microscopy, and quantified using Scion Image. High levels of VEGF mRNA were detected in astrocytes associated with developing vessels. We also detected strong expression of VEGF mRNA in the GCL at the incipient fovea prior to Fd 105, with peak labeling in the incipient fovea that declined with distance in nasal and temporal directions. By Fd 152 peak labeling was in two bands associated with development of the inner nuclear layer (INL) capillary plexus: in the inner INL where Müller and amacrine cell somas are located, and in the outer INL where horizontal cells are found. The findings suggest that at the incipient fovea the GCL is hypoxic, supporting the hypothesis that the adaptive significance of the fovea centralis is in ensuring adequate oxygen supply to neuronal elements initially located within the avascular region.

Vascular endothelial growth factor: a regulator of vascular morphogenesis in the Japanese quail embryo.

Experiments in mouse embryos indicate that a critical level of VEGF is required for normal vascular development, as mice lacking a single VEGF allele die at midgestation. Thus VEGF concentration may be a determinant of the size and location of major blood vessels during formation of the primary capillary plexus. Ectopic VEGF delivery was used to examine the effect of VEGF concentration on early vascular patterning in the quail embryo. VEGF was delivered by implanting VEGF-soaked heparin chromatography beads at three rostral-caudal locations in embryos with six somite pairs, which allowed us to study the effect of VEGF on different cellular activities. Ectopic VEGF resulted in significant changes in the vascular pattern at three rostral-caudal levels. Quantitation demonstrated an increased vascularity in the area of the implanted VEGF bead compared to the vascular pattern of embryos with control beads. Areas lateral to the dorsal aortae that are normally avascular became vascularized, and there was an apparent fusion between the dorsal aorta and lateral capillary plexus.

Fibroblast growth factor 2 promotes microvessel formation from mouse embryonic aorta.

To delineate the roles that oxygen and fibroblast growth factors (FGFs) play in the process of angiogenesis from the embryonic aorta, we cultured mouse embryonic aorta explants (thoracic level to lateral vessels supplying the mesonephros and metanephros) in a three-dimensional type I collagen gel matrix. During 8 days of culture under 5% O(2), but not room air, the addition of FGF2 to explants stimulated the formation of Gs-IB(4-)positive, CD31-positive, and Flk-1-positive microvessels in a concentration-dependent manner. FGF2-stimulated microvessel formation was inhibited by sequestration of FGF2 via addition of soluble FGF receptor (FGFR) chimera protein or anti-FGF2 antibodies. FGFR1 and FGFR2 were present on explants. Levels of FGFR1, but not FGFR2, were increased in embryonic aorta cultured under 5% O(2) relative to room air. Our data suggest that low oxygen upregulates FGFR1 expression in embryonic aorta in vitro and renders it more responsive to FGF2.

Microvascularization of the mucocutaneous junction of the nose.

The aim of this study was to describe the microvascularization of the area of junction located between the integuments of the nasal ala and the respiratory mucosa. This study is part of an overall study on the microvascularization of the mucocutaneous junctions of the head. It was undertaken on histological or clarified sections of noses from fetuses, newborns and adults whose vascular system was injected with Indian ink agar. The mucocutaneous junction of the nose shows similarities with the mucocutaneous junction of the oral cavity. Under a well-defined avascular and thick epithelium lies a vascular papillary network with typical loops less high than in the lips. The angioarchitectonics of superficial and deep vascular reticular networks is similar to that of the lips but they are less dense.

Microvascularization of the mucocutaneous junctions of the head in fetuses and neonates.

The mucocutaneous junctions of the head (oral, nasal and palpebral) are transitional zones between the integuments and the mucosa. Their microvascularization is studied in the heads of fetuses and neonates by injection of agarized China ink into the vascular system. These zones are situated deep with respect to the free edge of the oral or nasal cavity or relative to the free margin of the eyelid. They present cutaneous-type microvascularization with a papillary network and reticular networks. Long capillary loops connected to the deep reticular network are their main feature. In the lips and eyelids, the morphology of the networks and their relationship with the orbicular muscles are suggestive of a functional structure.