PPAR-γ with its anti-inflammatory and anti-fibrotic action could be an effective therapeutic target in IBD.

OBJECTIVE: Intestinal fibrosis is a process characterized by an excessive deposition of Extracellular Matrix (ECM) proteins by activated myofibroblasts and represents a consequence of a chronic inflammation that usually occurs during Inflammatory Bowel Disease (IBD). The relationship between inflammation and fibrosis in IBD remains still unclear and nevertheless the recent pharmacological progresses, currently the only resolutive therapeutic strategy is surgery, especially when complications (stricture, stenosis and obstruction of intestinal tracts) appear. As many different cellular types and molecular mechanisms are implicated in the pathogenesis of IBD, the identification of molecules able to counteract this process could be crucial. MATERIALS AND METHODS: This is a literature review of several articles published on PubMed databases. RESULTS: A number of researches suggest that Proliferator-Activated Receptor-gamma (PPAR-γ) has both anti-inflammatory and anti-fibrotic effects in many organs. PPAR-γ has been demonstrated to be able to downregulate pro-inflammatory cytokines production such as Interleukin (IL)-4,-5,-6 but also to interfere with profibrotic molecules as Platelet-Derived Growth Factor (PDGF), IL-1 and Transforming Growth Factor Beta (TGF-ß), the main promoter of fibrosis. In preliminary clinical trials and in experimental models of intestinal fibrosis, natural and chemical PPAR-γ ligands have ameliorated the fibrotic process. CONCLUSIONS: Since PPAR-γ could play a crucial role in the development of the disease, the research of new molecules, capable of ameliorating both inflammation and fibrosis lesions, as PPAR-γ agonists, could represent a valid and effective therapeutic approach for the prevention and treatment of IBD and intestinal fibrosis.

Correction to: The first-in-class alkylating deacetylase inhibitor molecule tinostamustine shows antitumor effects and is synergistic with radiotherapy in preclinical models of glioblastoma.

The original article [1] contained an error whereby Fig. 4 displayed incorrect magnification scales.

Changes in muscularis propria of anterior vaginal wall in women with pelvic organ prolapse.

The objective of this study was to evaluate the morphological and immunohistochemical alterations of tissue removed from the upper third of anterior vaginal wall in a sample group of the female population presenting homogenous risk factors associated with Pelvic Organ Prolapse (POP). The case study consisted of 14 patients with POP and there were 10 patients in the control group. Patient selection was carried on the basis of specific criteria and all of the patients involved in the study presented one or more of the recognized POP risk factors. Samples were taken from POP patients during vaginal plastic surgery following  colpohysterectomy, and from control patients during closure of the posterior fornix following hysterectomy. Samples were processed for histological and  immunohistochemical analyses for Collagen I and Collagen III, α-Smooth Muscle Actin (α-SMA), Platelet-Derived-Growth-Factor (PDGF), matrix metalloproteinase 3 (MMP3), Caspase3. Immunofluorescence analyses for Collagen I and III and PDGF were also carried out. In prolapsed specimens our results show a disorganization of smooth muscle cells that appeared to have been displaced by an increased collagen III deposition resulting in rearrangement of the muscularis propria architecture. These findings suggest that the increase in the expression of collagen fibers in muscularis could probably due to a phenotypic switch resulting in the dedifferentiation of smooth muscle cells into myofibroblasts. These alterations could be responsible for the compromising of the dynamic functionality of the pelvic floor.

Contribution of intestinal smooth muscle to Crohn's disease fibrogenesis.

Mesenchymal cells transdifferentiation and extracellular matrix deposition are involved in the fibrotic process of Crohn's disease (CD). Mesenchymal smooth muscle cells (SMCs) de-differentiation, driven by Platelet-derived growth factor (PDGF) that counteracts Transforming growth factor (TGF-ß) has been studied in vascular muscle. The role of SMCs in intestinal fibrogenesis is still not clearly elucidated. Aim of the study was to evaluate the possible myogenic contribution to CD fibrotic process through the comparative analysis of histological, morphometric and molecular alterations occurring in human smooth muscle. Full thickness specimens were obtained from CD (non-involved and stenotic tracts) and healthy (control) ileum. Tissues were processed for histological and immunohistochemical (IHC) analyses and SMCs were isolated from the muscularis propria for morphofunctional and molecular (qPCR) analyses. CD stenotic ileum showed a significant increased thickness of all layers compared to CD non-involved and control ileum. IHC revealed an overexpression of α-smooth muscle actin and collagens I-III throughout all intestinal layers only in stenotic tracts. The two growth factors, PDGF and TGF-ß, showed a progressive increase in expression in the muscle layer from CD non-involved to stenotic tracts. Freshly isolated SMCs presented alterations in CD non-involved tracts that progressively increased in the stenotic tracts consisting in a statistical increase in mRNA encoding for PDGF-ß and collagen III, paralleled to a decrease in TGF-ß and Tribbles-like protein-3 mRNA, and altered morphofunctional parameters consisting in progressive decreases in cell length and contraction to acetylcholine. These findings indicate that intrinsic myogenic alterations occur in CD ileum, that they likely precede stricture formation, and might represent suitable new targets for anti-fibrotic interventions.

Can we prevent, reduce or reverse intestinal fibrosis in IBD?

Intestinal fibrosis is a common complication of in inflammatory bowel disease (IBD) and can occur in both ulcerative colitis (UC) and Crohn's disease (CD), but is much more prevalent in CD. Fibrosis is a consequence of local chronic inflammation and is characterized by abnormal deposition of extracellular matrix (ECM) proteins producted by activated myofibroblasts. Current anti-inflammatory therapies used in IBD do not prevent nor they reverse established fibrosis and strictures. Despite the therapeutic advance in the treatment of IBD in the last two decades, the incidence of intestinal strictures in CD has not significantly changed. This implies that control of intestinal inflammation does not necessarily affect the associated fibrotic process. The conventional view that intestinal fibrosis is an inevitable and irreversible process in patients with IBD is progressively changing in light of improved understanding of the cellular and molecular mechanisms that underline the pathogenesis of fibrosis. Comprehension of the mechanisms of intestinal fibrosis may pave the way for the developments of anti-fibrotic agents and of new possible therapeutic approches in IBD. Nevertheless, there are important clinical issues that need further investigations, in particular the identification of factors relevant for the development of the intestinal fibrosis in IBD and the need of accurate and effective monitoring of the fibrotic progression and of effectiveness of the new proposed treatments.

Localization of ανß6 integrin-TGF-ß1/Smad3, mTOR and PPARγ in experimental colorectal fibrosis.

A simultaneous action of several pro-fibrotic mediators appears relevant in the development of fibrosis. There are evidences that transforming growth factor-ß (TGF-ß)/Smad3 pathway forms with αvß6 integrin, mammalian target of Rapamycin (mTOR) and peroxisome proliferator-activated receptor-γ (PPARγ) a complex signalling network with extensive crosstalk and strong effects on fibrosis development. The present study evaluated the expression of TGFß, Smad3, αvß6 integrin, mTOR and PPARγ in 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced colorectal fibrosis in Smad3 wild-type (WT) and null mice. Smad3 WT mice treated with TNBS developed a marked colorectal fibrosis and showed a concomitant up-regulation of TGFß, Smad3, αvß6 and mTOR and a reduction of PPARγ expression. On the other hand, Smad3 Null mice similarly treated with TNBS did not develop fibrosis and showed a very low or even absent expression of TGFß, Smad3, αvß6 and mTOR and a marked over-expression of PPARγ. At the same time the expression of α-smooth muscle actin (a marker of activated myofibroblasts), collagen I-III and connective tissue growth factor (a downstream effector of TGFß/Smad3-induced extracellular matrix proteins) were up-regulated in Smad3 WT mice treated with TNBS compared to Null TNBS-treated mice. These preliminary results suggest a possible interaction between these pro-fibrotic molecules in the development of intestinal fibrosis.

Boswellia serrata and Salvia miltiorrhiza extracts reduce DMN-induced hepatic fibrosis in mice by TGF-beta1 downregulation.

BACKGROUND: Hepatic fibrosis is characterised by a progressive accumulation of fibrillar extracellular matrix (ECM) proteins, including collagen that occurs in chronic liver diseases. Transforming growth factor-beta1 (TGF-beta)/Smad3 signalling plays a major role in tissue fibrogenesis acting as a potent stimulus of ECM accumulation. AIM: To evaluate the effects of a combined therapy with anti-inflammatory Boswellia and anti-fibrotic Salvia extracts on the course of chronic hepatitis-associated fibrosis induced by dimethylnitrosamine (DMN) in mice, as well as on the hepatic expression of TGF-beta1 and Smad proteins. METHODS: Chronic hepatitis-associated fibrosis was induced in mice by intraperitoneal DMN administration. Mice were assigned to 5 groups: controls; DMN without any treatment; DMN treated orally with Boswellia extracts (50 mg/kg/day); DMN treated orally with Salvia extracts (150 mg/ kg/day); DMN treated orally with both Boswellia (50 mg/kg/day) and Salvia extracts (150 mg/kg/ day). The liver was excised for macroscopic examination and histological, morphometric and immunohistochemical (IHC) analyses. For IHC, alpha-smooth muscle actin (alpha-SMA), collagen types I-III, TGF-beta1, connective tissue growth factor (CTGF), Smad3, Smad7, CD3, PCNA and TUNEL antibodies were used. RESULTS: The combined oral administration of Boswellia and Salvia extracts improved the course and macroscopic findings of DMN-induced chronic hepatitis-associated fibrosis. The histological severity of the hepatic fibrosis showed a marked improvement following treatment and was associated with a reduction in the hepatic expression of alpha-SMA, collagen I-III, CTGF, TGF-beta1, Smad3, and Smad7. CONCLUSIONS: These data demonstrate that co-treatment of Boswellia plus Salvia extracts is effective in preventing hepatic fibrosis in DMN-induced chronic hepatitis. The anti-fibrotic properties are mainly related to Salvia extracts and appear to be mediated by the inhibition of the TGF-beta1/Smad3 pathway.

Smad3 loss confers resistance to the development of trinitrobenzene sulfonic acid-induced colorectal fibrosis.

BACKGROUND: Transforming growth factor-beta (TGF-beta)/Smad3 signalling plays a central role in tissue fibrogenesis, acting as a potent stimulus of extracellular matrix (ECM) protein accumulation. The aim of this study was to evaluate the potential role of Smad3 in the pathogenesis of colonic fibrosis induced by trinitrobenzene sulfonic acid (TNBS) in Smad3 null mice. MATERIALS AND METHODS: Chronic colitis-associated fibrosis was induced in 15 Smad3 null and 13 wild-type mice by intra-rectal administration of TNBS. Each mouse received an incremental dose of TNBS (0.5-1.0 mg per week) over a 6-week period. The colon was excised for macroscopic examination and histological, morphometric and immunohistochemical analyses. For immunohistochemistry, alpha-smooth muscle actin (alpha-SMA), collagen types I-III, TGF-beta1, connective tissue growth factor (CTGF), Smad3, Smad7, and CD3 antibodies were used. RESULTS: At macroscopic examination, the colon of Smad3 wild-type mice appeared significantly harder, thicker and shorter than that of the Smad3 null mice. Of the wild-type mice, 50% presented colonic adhesions and strictures. Histological and morphometric evaluation revealed a significantly higher degree of colonic fibrosis and accumulation of collagen in the Smad3 wild-type compared to null mice, whereas the degree of colonic inflammation did not differ between the two groups of mice. Immunohistochemical evaluation showed a marked increase in CTGF, collagen I-III, TGF-beta and Smad3 staining in the colon of Smad3 wild-type compared to null mice, whereas Smad7 was increased only in null mice. CONCLUSIONS: These results indicate that Smad3 loss confers resistance to the development of TNBS-induced colonic fibrosis. The reduced fibrotic response appears to be due to a reduction in fibrogenic mesenchymal cell activation and ECM production and accumulation. Smad3 could be a novel target for potential treatment of intestinal fibrosis, especially in inflammatory bowel disease.

Prevention of colonic fibrosis by Boswellia and Scutellaria extracts in rats with colitis induced by 2,4,5-trinitrobenzene sulphonic acid.

BACKGROUND: Currently, no effective preventive measures or medical therapies are available for intestinal fibrosis and, thus, surgery remains the only available strategy in the management of fibrostenotic enteropathies, especially Crohn's disease. The aim of this study was to evaluate the efficacy of a combined therapy of anti-inflammatory Boswellia and antifibrotic Scutellaria extracts on the development of colonic fibrosis in rats. MATERIALS AND METHODS: Chronic colonic inflammation-associated fibrosis was induced in rats by intracolonic administration of 2,4,5-trinitrobenzene sulphonic acid (TNBS). Sixty-four healthy male Sprague-Dawley rats were assigned to five groups: 8 controls, 14 TNBS, 14 TNBS orally treated with Boswellia extracts (50 mg kg(-1) day(-1)), 14 TNBS orally treated with Scutellaria extracts (150 mg kg(-1) day(-1)), and 14 TNBS orally treated with both Boswellia (50 mg kg(-1) day(-1)) and Scutellaria extracts (150 mg kg(-1) day(-1)). The colon was removed after 21 days of treatment and assessed by macroscopic, histological, morphometric and immunohistochemical analyses. For immunohistochemical analysis, alpha-smooth muscle actin (alpha-SMA), collagen types I-III, connective tissue growth factor (CTGF), transforming growth factor-beta1 (TGF-beta1), Smad3, Smad7 and CD3 antibodies were used. RESULTS: Combined oral administration of Boswellia and Scutellaria significantly improved the course and macroscopic findings of TNBS-induced chronic colitis assessed by disease activity index, colon weight, length, adhesions, strictures, dilatation, thickness, oedema, ulcerations and extension of damage. The histological severity of the colonic fibrosis was also notably improved by the treatment and associated with a significant reduction in the colonic expression of alpha-SMA, collagen I-III, CTGF, TGF-beta1, Smad3, and Smad7. CONCLUSIONS: These data demonstrate that the prophylactic administration of anti-inflammatory Boswellia and antifibrotic Scutellaria extracts is effective in preventing colonic fibrosis in TNBS-induced colitis. Their antifibrotic mechanism of action seems to be mediated by the inhibition of TGF-beta1/Smad3 pathway.

Smad3-null mice lack interstitial cells of Cajal in the colonic wall.

BACKGROUND: Transforming growth factor-beta (TGF-beta)/Smad's signalling pathway plays a pivotal role in organogenesis, oncogenesis, inflammation, repair and fibrosis. The aim of this study was to evaluate the morphology of muscle layers and the density and distribution of interstitial cells of Cajal (ICC) in the colon of Smad3 knockout mice. MATERIALS AND METHODS: Eighteen Smad3 wild-type mice and 12 null mice were sacrificed at age 4 months and the colons were collected for histology (Haematoxilin-Eosin, Masson thrichrome and Gomori silver staining), morphometry and immunohistochemistry (IHC) analysis. For IHC we used the c-Kit, alpha-smooth muscle actine (alpha-SMA), vimentin, desmin and neuronal cocktail (S-100, NSE, neurofilament 200) antibodies. RESULTS: When sacrificed, 40% of the null mice showed different degrees of colon dilatation when compared with the wild-type. Histological and morphometric evaluation revealed a significant reduction in muscle layer thickness of the colon in all the null mice when compared with the wild-type. Immunohistochemistry evaluation showed a marked reduction, or even absence, of c-Kit immunoreactivity, which identifies ICC, in the colon of all the null mice, compared with the wild-type. CONCLUSIONS: Smad3 null mice showed a marked reduction, or even absence, of ICC in the colon together with a concomitant reduction of intestinal smooth muscle layer thickness. This data could account for the colonic dilation observed in approximately 40% of the Smad3 null mice. Alteration of intestinal smooth muscle layers and ICC could also be involved in the resistance of the Smad3 null mice to develop colonic fibrosis.

Slime production by clinical isolates of Blastoschizomyces capitatus from patients with hematological malignancies and catheter-related fungemia.

In order to expand the present knowledge of the pathogenic potential of Blastoschizomyces capitatus in central venous catheter (CVC)-related bloodstream infections, six strains of the organism recovered from three leukemic patients with CVC-related fungemia in different years were investigated. Isolates and control strains were tested for their genetic relatedness and for their ability to produce slime in glucose-containing solutions. DNA restriction enzyme analysis revealed that all strains of B. capitatus were identical, whereas slime production assays and examination of ex vivo material showed that they were able to produce large amounts of slime. Slime production may therefore play a relevant pathogenic role in cases of CVC-related fungemia caused by B. capitatus.

Peyer's patches epithelium in the rat: a morphological, immunohistochemical, and morphometrical study.

The epithelial layer covering lymphoid follicles of Peyer's patches consists of cells with a different surface morphology. Some of these cells have been described as a distinct cytotype, the so-called M cells. In order to resolve the controversy on the specific morphological and biochemical markers of M cells, structural, ultrastructural, and morphometrical study of the epithelium covering the rat Peyer's patches were performed. Peyer's patches from healthy rats were processed for light microscopy, immunohistochemistry, in situ nick-end labeling (TUNEL), and scanning and transmission electron microscopy. A morphometric study was also performed to evaluate microvillus density, length, and number of lysosomes in different areas of the epithelium. Peyer's patches were covered by simple columnar/cubical dome epithelium (DE). Scarce goblet cells and a large number of enterocytes were observed. Ultrastructural observations revealed that the DE showed cells with different morphology. The density and length of microvilli and the lysosome number varied along the whole dome without significant differences. The DE cells characterized by short and disorganized microvilli appeared always in close spatial relationship with lymphocytes. In conclusion, the concept that distinct cell types (enterocytes and M cells) can be identified in the rat DE does not appear to be valid based on morphological criteria. It seems correct to consider that in rat Peyer's patches the presence of scarce goblet cells and a large number of enterocytes showing dynamic morphofunctional modifications is related to the functional state and/or to cell cycle.

Deafferentation-induced apoptosis of neurons in thalamic somatosensory nuclei of the newborn rat: critical period and rescue from cell death by peripherally applied neurotrophins.

This study shows that unilateral transection of the infraorbital nerve (ION) in newborn (P0) rats induces apoptosis in the contralateral ventrobasal thalamic (VB) complex, as evidenced by terminal transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) and electron miscroscopy. Double-labelling experiments using retrograde transport of labelled microspheres injected into the barrel cortex, followed by TUNEL staining, show that TUNEL-positive cells are thalamocortical neurons. The number of TUNEL-positive cells had begun to increase by 24 h postlesion, increased further 48 h after nerve section, and decreased to control levels after 120 h. Lesion-induced apoptosis in the VB complex is less pronounced if ION section is performed at P4, and disappears if the lesion is performed at P7. This time course closely matches the critical period of lesion-induced plasticity in the barrel cortex. Nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF), applied on the ION stump alone or in combination, are able to partially rescue thalamic neurons from apoptosis. Total cell counts in the VB complex of P7 animals that underwent ION section at P0 confirm the rescuing effect of BDNF and NGF. Blockade of axonal transport in the ION mimics the effect of ION section. These data suggest that survival-promoting signals from the periphery, maybe neurotrophins, are required for the survival of higher-order neurons in the somatosensory system during the period of fine-tuning of neuronal connections. We also propose that anterograde transneuronal degeneration in the neonatal rat trigeminal system may represent a new animal model for studying the pathways of programmed cell death in vivo.

Dextran sulfate sodium (DSS) colitis in rats: clinical, structural, and ultrastructural aspects.

Aim of this study was to assess the structural, ultrastructural, immunohistochemical, and clinical aspects in Sprague-Dawley rats with dextrane sulfate sodium (DSS)-induced colitis. Colitis was induced in Sprague-Dawley rats by seven days of DSS oral administration followed by seven days of tap water only (for one, two and three cycles). Controls were fed with water only. Segments of proximal, mid-, and distal colon of each animal were adequately prepared for light and scanning electron microscope observations. The severity of the lesions was scored histologically. For immunohistochemical study, a cocktail of S-100, NSE, and antineurofilament antibodies was used. Symptoms such as weight, feces consistency, diarrhea, hematochezia were recorded daily. From a clinical point of view symptoms appeared significantly later after the first cycle than after the second and third cycles and lasted significantly longer in the second and third cycles. Treated rats showed a slower weight gain rate by 20% compared to controls, and the whole colon length appeared to be significantly shorter after colitis induction compared to controls. Structural observations by light microscopy showed prominent involvement of the distal colon. Immunohistochemical study of both submucosal and myoenteric nerve plexuses was similar to controls. Scanning electron microscope observations of the colonic mucosal surface in colitis rats showed a complete subversion of its architecture, characterized by dilatations of gland crypt openings, dropout of goblet cells, and inhomogeneous distribution or lack of microvilli. These were most evident after the third cycle. In conclusion, experimental DSS colitis in SD rats appeared to be highly reproducible and shared most features with human UC, not only from a structural and clinical but also from an ultrastructural point of view.

Onychomycosis caused by Blastoschizomyces capitatus.

Blastoschizomyces capitatus was cultured from the nail of a healthy patient with onychomycosis. The identity of the isolate was initially established by standard methods and ultrastructural analysis and was verified by molecular probing. Strains ATCC 200929, ATCC 62963, and ATCC 62964 served as reference strains for these analyses. To our knowledge, this is the first case of nail infection secondary to paronychia caused by this organism reported in the English literature.

Felodipine protects human atrial muscle from hypoxia-reoxygenation dysfunction: a force-frequency relationship study in an in vitro model of stunning.

AIMS: We aimed at investigating contractile changes after hypoxia-reoxygenation and dobutamine challenge in superfused human atrial pectinate muscle to see whether high versus low stimulation rate during hypoxia might account for outcome differences compatible with the definition of an in vitro model of myocardial stunning and whether pretreatment with the dihydropyridine Ca2+ entry blocker felodipine might afford protection. METHODS: Human right atrial trabeculae obtained from adult patients were superfused in an organ bath with oxygenated (O2 content 16 ml/l) and modified (NaHCO3 25.7 mmol/l) Tyrode's solution at 37 degrees C. Dobutamine (1 nmol/l to 10 micromol/l) was superfused in 10 oxygenated preparations to select the optimal drug concentration to be used in another 22 which were randomized. Group (A) consisted of time-related controls (Tyrodes's solution for 225 min at cycle length (CL) 1600 ms and no dobutamine). There were two test groups, respectively: (B) low (1600 ms CL) and (C) high (400 ms CL) stimulation rate. After 60 min of stabilization, in groups B and C, hypoxic superfusion (O2 content 5 ml/l) lasted 60 min, then reoxygenation (60 min) and dobutamine challenge (1 micromol/l, 15 min) were performed. Analysis of variance for repeated measures with the Greenhouse-Geisser correction, and a repeated measures model with structured covariance (preparation mass, length, width and time-varying time to peak tension) matrices were used whereby grouping (G), time (T) and G x T interaction were weighted. Force-frequency relationship and post-pausal potentiation were studied after each phase. Electrophysiology, histomorphometry and electron microscopy were carried out (n=6). Felodipine (0.1 micromol/l, n=5) pretreatment (15 min before hypoxia) was given in parallel experiments. RESULTS: Time-related controls showed approximately 10% per hour decrease of developed tension and the Paradise test provided approximately 80% of control values. In test groups (as compared to baseline values) contractility was decreased approximately 65% after hypoxia-reoxygenation and it increased approximately 25% after dobutamine (G, 0.0065

Nasal vascularization: experiences using the microcorrosion technique in human foetuses.

The authors have studied the three-dimensional aspect of the vascular architecture of the nasal mucosa, using the microcorrosion method followed by scanning electron microscopical observation of casts of the vascular networks in both the septum and the lateral part of the nose. Batson's compound was introduced into the vascular system through the ascending aorta, in order to obtain a replica of the nasal mucosa vessels. Twelve- to 24-week-old foetuses obtained from spontaneous abortions were used for this purpose.

[Arteriovenous anastomosis in nasal cavities using microcorrosion technique]. / Studio delle anastomosi artero-venose delle cavità nasali con tecnica microcorrosiva.

In the present study the morphology of arteriovenous anastomoses in the nasal area are analyzed using the microcorrosion technique. This technique calls for perfusion of the vascular system, passing through the left ventricle, with Batson's of the vessels. For the first time in the microcorrosion study of the nasal vascular network human fetuses (from the 12th to 24th week of intrauterine life) obtained from spontaneous abortions were used as well as rats weighing from 250 to 300 gr. The animals were anesthetized with sodium thiopental prior to administration of the resin. A specimen containing the facial muscles, the nasal pyramid, the maxillary bone and the palatine bones was excised. Then, from this specimen the nasal septum and the two lateral portions of the nose were obtained. The bony and soft perivascular tissues were removed by placing the casts in an aqueous 20% KOH solution. Finally the corrosion cases were observed under a scanning electron microscope (EM). Within the nasal cavities the microcorrosion technique makes it possible to identify three different vascular layers: superficial, intermediate and deep. In the latter it proved possible to visualize the two types of arteriovenous anastomoses: i.e. simple and complex. On the basis of both vascular course and the impressions left by the endothelial cell nuclei it proved possible to differentiate between the arterial and venous portions of the anastomoses.