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Alpha-synuclein (α-syn) is a presynaptic neuronal protein and its structural alterations play an important role in the pathogenesis of neurodegenerative diseases, such as Parkinson’s disease (PD). It has been originally described in the brain and aggregated α-syn has also been found in the peripheral nerves including the enteric nervous system (ENS) of PD patients. ENS is a network of neurons and glia found in the gut wall which controls gastrointestinal function independently from the central nervous system. Moreover, two types of epithelial cells are crucial in the creation of an interface between the lumen and the ENS: they are the tuft cells and the enteroendocrine cells (EECs). In addition, the abundant enteric glial cells (EGCs) in the intestinal mucosa play a key role in controlling the intestinal epithelial barrier. Our aim was to localize and characterize the presence of α-syn in the normal human jejunal wall. Surgical specimens of proximal jejunum were collected from patients submitted to pancreaticoduodenectomy and intestinal sections underwent immunohistochemical procedure. Alpha-syn has been found both at the level of ENS and the epithelial cells. To characterize α-syn immunoreactive epithelial cells, we used markers such as choline acetyltransferase (ChAT), useful for the identification of tuft cells. Then we evaluated the co-presence of α-syn with serotonin (5-HT), expressed in EECs. Finally, we used the low-affinity nerve growth factor receptor (p75NTR), to detect peripheral EGCs. The presence of α-syn has been demonstrated in EECs, but not in the tuft cells. Additionally, p75NTR has been highlighted in EECs of the mucosal layer and co-localized with α-syn in EECs but not with ChAT-positive cells. These findings suggest that α-syn could play a possible role in synaptic transmission of the ENS and may contribute to maintain the integrity of the epithelial barrier of the small intestine through EECs.

Cholangiocarcinoma (CCA) represents the second most common primary hepatic malignancy and originates from the neoplastic transformation of the biliary cells. The intrahepatic subtype includes two morpho-molecular forms: large-duct type intrahepatic CCA (iCCA) and small-duct type iCCA. Iron is fundamental for the cellular processes, contributing in tumor development and progression. The aim of this study was to evaluate iron uptake, storage, and efflux proteins in both lipopolysaccharide-inflamed small and large cholangiocytes as well as in different iCCA subtypes. Our results show that, despite an increase in interleukin-6 production by both small and large cholangiocytes, ferroportin (Fpn) was decreased only in small cholangiocytes, whereas transferrin receptor-1 (TfR1) and ferritin (Ftn) did not show any change. Differently from in vitro models, Fpn expression was increased in malignant cholangiocytes of small-duct type iCCA in comparison to large-duct type iCCA and peritumoral tissues. TfR1, Ftn and hepcidin were enhanced, even if at different extent, in both malignant cholangiocytes in comparison to the surrounding samples. Lactoferrin was higher in large-duct type iCCA in respect to small-duct type iCCA and peritumoral tissues. These findings show a different iron handling by inflamed small and large cholangiocytes, and small and large-duct type iCCA. The difference in iron homeostasis by the iCCA subtypes may have implications for the tumor management.

The neurohypophysial hormone arginine vasopressin (AVP) acts by three distinct receptor subtypes: V1a, V1b, and V2. In the liver, AVP is involved in ureogenesis, glycogenolysis, neoglucogenesis and regeneration. No data exist about the presence of AVP in the biliary epithelium. Cholangiocytes are the target cells in a number of animal models of cholestasis, including bile duct ligation (BDL), and in several human pathologies, such as polycystic liver disease characterized by the presence of cysts that bud from the biliary epithelium. In vivo, liver fragments from normal and BDL mice and rats as well as liver samples from normal and ADPKD patients were collected to evaluate: (i) intrahepatic bile duct mass by immunohistochemistry for cytokeratin-19; and (ii) expression of V1a, V1b and V2 by immunohistochemistry, immunofluorescence and real-time PCR. In vitro, small and large mouse cholangiocytes, H69 (non-malignant human cholangiocytes) and LCDE (human cholangiocytes from the cystic epithelium) were stimulated with vasopressin in the absence/presence of AVP antagonists such as OPC-31260 and Tolvaptan, before assessing cellular growth by MTT assay and cAMP levels. Cholangiocytes express V2 receptor that was upregulated following BDL and in ADPKD liver samples. Administration of AVP increased proliferation and cAMP levels of small cholangiocytes and LCDE cells. We found no effect in the proliferation of large mouse cholangiocytes and H69 cells. Increases were blocked by preincubation with the AVP antagonists. These results showed that AVP and its receptors may be important in the modulation of the proliferation rate of the biliary epithelium.

Liver transplantation and cholangiocarcinoma induce biliary dysfunction following ischemia reperfusion (IR). The function of the intrahepatic biliary tree is regulated by both autocrine and paracrine factors. The aim of the study was to demonstrate that IR-induced damage of cholangiocytes is associated with altered expression of biliary angiogenic factors. Normal and bile duct ligation rats underwent 24-h sham or hepatic reperfusion after 30 min of transient occlusion of the hepatic artery (HAIR) or portal vein (PVIR) before collecting liver blocks and cholangiocyte RNA or protein. We evaluated liver histology, biliary apoptosis, proliferation and expression of VEGF-A/C, VEGFR-2/3, Ang-1/2, and Tie-1/2 in liver sections and isolated small and large cholangiocytes. Normal rat intrahepatic cholangiocyte cultures (NRICC) were maintained under standard conditions in normoxic or under a hypoxic atmosphere for 4 h and then transferred to normal conditions for selected times. Subsequently, we measured changes in biliary proliferation and apoptosis and the expression of VEGF-A/C and VEGFR-2/3. In vivo, HAIR (but not PVIR) induced damage of large bile ducts and decreased proliferation and secretin-stimulated cAMP levels. HAIR-induced damage of large bile ducts was associated with increased expression of VEGF-A/C, VEGFR-2/3, Ang-1/2, and Tie-1/2. In vitro, under hypoxic conditions, there was increased apoptosis and reduced proliferation of NRICC concomitant with enhanced expression of VEGF-A/C and VEGFR-2/3. The functional damage of large bile ducts by HAIR and hypoxia is associated with increased expression of angiogenic factors in small cholangiocytes, presumably due to a compensatory mechanism in response to biliary damage.

Cholangiocarcinoma (CCA) is an aggressive biliary tract malignancy with limited treatment options and low survival rates. The intrahepatic subtype comprises two forms: mucin-iCCA and mixed-iCCA. Epidermal growth factor-like domain multiple (EGFL7) is overexpressed in less differentiated liver tumors. The aim of this study was to assess the presence of EGFL7 due to its possible role in the growth of CCA. Hematoxylin and Eosin and periodic acid-Schiff staining were used to evaluate the morphological aspects and glycogen deposition. Immunohistochemistry and immunofluorescence were performed to identify the presence of EGFL7 both in tumor sections ex vivo and in appropriate cell lines in culture. We found that EGFL7 is expressed in malignant cholangiocytes of mixed-iCCA and absent in mucin-iCCA. In conclusion the expression of EGFL7 might be useful in the classification of CCA subtypes.

Angiogenesis plays a fundamental role in tumor growth and progression. It is regulated by several growth factors, including vascular endothelial growth factor protein family (VEGF) and its receptors, which are probably the most important factors responsible for the development of new vessels. The VEGF family includes several members: VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, placental growth factor (PlGF), and their receptors VEGFR-1, VEGFR-2 and VEGFR-3. Other relevant factors are represented by angiopoietins, thrombospondin-1, and endothelins. However, since the therapeutic benefit associated with VEGF-targeted therapy is really complex, a better understanding of these pathways will lead to future advances in the use of these agents for clinic management of tumors. Here we present a review regarding the role of angiogenic factors in cholangiocarcinoma, which arise from cholangiocytes, the epithelial cells of bile ducts. They are rare and aggressive neoplasms with a poor prognosis and limited treatment options, classified as intrahepatic, perihilar, and distal cholangiocarcinoma based on their anatomical location. Therefore, the identification of specific signaling pathways or new tumor biomarkers is crucial in order to develop more effective anti-angiogenic therapies.

Ischemic injury by hepatic artery ligation (HAL) during obstructive cholestasis induced by bile duct ligation (BDL) results in bile duct damage, which can be prevented by administration of VEGF-A. The potential regulation of VEGF and VEGF receptor expression and secretion by bile acids in BDL with HAL is unknown.We evaluated whether taurocholic acid (TC) can prevent HAL-induced cholangiocyte damage via the alteration of VEGFR-2 and/or VEGF-A expression.Utilizing BDL, BDL+TC, BDL+HAL, BDL+HAL+TC, and BDL+HAL+wortmannin+TC treated rats, we evaluated cholangiocyte apoptosis, proliferation, and secretion as well VEGF-A and VEGFR-2 expression by immunohistochemistry. In vitro, we evaluated the effects of TC on cholangiocyte secretion of VEGF-A and the dependence of TC-induced proliferation on the activity of VEGFR-2.In BDL rats with HAL, chronic feeding of TC prevented HAL-induced loss of bile ducts and HAL-induced decreased cholangiocyte secretion. TC also prevented HAL-inhibited VEGF-A and VEGFR-2 expression in liver sections and HAL-induced circulating VEGF-A levels, which were blocked by wortmannin administration. In vitro, TC stimulated increased VEGF-A secretion by cholangiocytes, which was blocked by wortmannin and stimulated cholangiocyte proliferation that was blocked by VEGFR-2 kinase inhibitor.TC prevented HAL-induced biliary damage by upregulation of VEGF-A expression.

The aim of this work is to investigate the growth of the vasculature in the rat humeral head cartilage after the initial development of the secondary ossification centre until the adult organization. Rats aging from 5 weeks to 12 months were used. Histological observations on humeral heads were implemented with morphometrical analysis. Subsequently, vascular corrosion cast, that permits a three-dimensional observation of the vasculature, were prepared and observed by scanning electron microscopy. In young animals the epiphysis contains thin bone trabeculae and most of the epiphysis is occupied by bone marrow spaces. With age, the bone trabeculae progressively enlarge up to double their thickness. The percentage of bone tissue increases from 33.6 to 58.6% of the entire epiphysis, while the bone marrow spaces tend to increase very little in their mean dimension. Vascular corrosion casts show that the epiphyseal microcirculation is well distinguished from that of the diaphysis, and arises from the vessels present in the capsule and the periosteal networks. In young animals the only capillaries are bone marrow sinusoids and few subchondral capillaries. In adult animals small vessels run between the clusters of sinusoids forming the trabecular circulation. Capillary sprouts from sinusoids are always observed both in the young and adult animals. Thus, in adult rats different proper microcirculatory districts can be distinguished in the epiphysis: (a) the sinusoidal network, that supplies the hematopoiesis of the bone marrow and the adjacent osteogenic tissue; (b) the bone tissue microcirculation, limited to small vessels that supply the metabolism and the remodelling of the bone tissue. The reported microvascular organization and its adaptation to the epiphyseal growth represent the morphological basis for understanding the reciprocal interaction among the different tissues in developing and adult rat epiphysis.

Background Little is known about the organization of microcirculation in flat bones in comparison with long bones. This study, therefore, helps us to determine the design of this vascular system in flat bones in relation to their structure and function. Methods The organization of microvasculature in parietal, scapula, and ileum bones of 15 young sexually mature rats, aged 6–7 weeks, was studied by light and scanning electron microscopy (SEM) from vascular corrosion cast (vcc), a resin-cast obtained material. Results Our observations show that the pattern of the microcirculation in flat bones is different in the thick and thin parts of such bones. Where the bone is thinner than 0.4 mm, only periosteal and dural network exist. Larger vessels which do not form a real network connect the two tables of the bones in these regions. In thicker areas, the organization of the microvasculature is similar to that in long bones, with distinct periosteal, cortical and bone marrow networks. Moreover, in different bones, outer networks show slightly different characteristics according to the different adjacent structures (dura mater, muscles etc.). Different types of vessels were recognized by comparing their different diameter, course and endothelial imprints. Conclusions The microvascular patterns of the flat bones are strongly influenced by the bone thickness. The different microvascular systems can interact both with the bone modelling and remodeling and with the variable metabolic needs, modifying the microvascular pattern and the blood flow. This is even more important in view of the reciprocal influence of the different networks within the same bone. Anat. Rec. 247:462–471, 1997. © 1997 Wiley-Liss, Inc.

Hepatic microcirculation has been related to liver function in several studies. The principle of this relationship lies in the sequential distribution of blood from the feeding vessels of the hepatic acinus to the central vein. This study was undertaken to investigate the progressive changes at different sites of the liver microvascular bed in the developing cirrhosis, both by light microscopy and scanning electron microscopy of corrosion casts. Experimental cirrhosis was induced with intragastric carbon tetrachloride. The most important vascular changes progressively observed are the reduction of the distance between the pre- and postsinusoidal vessels, the presence of newly formed shunting vessels bypassing the sinusoids and, finally, the development of a perinodular vascular plexus composed of pre- and postsinusoidal vessels. Newly formed vessels grow through preformed tissue septa. These vascular modifications make any zonal gradient hardly possible. The loss of the zonal gradient of perfusion could highly modify liver function, along with the structural changes of hepatic laminae. Hepatocyte regeneration cannot recover the original vascular relationships: this makes the morphological and functional destructuralization of cirrhotic liver irreversible. (HEPATOLOGY 1993;17:477–485.)

The organization of the hepatic microvascular network has been widely studied in recent years, especially with regard to cirrhosis. This research has enabled us to recognize the distinctive vascular patterns in the cirrhotic liver, compared with the normal liver, which may explain the cause of liver dysfunction and failure. The aim of this study was to compare normal and cirrhotic rat livers by means of a quantitative mathematical approach based on fractal and Fourier analyses performed on photomicrographs and therefore on discriminant analysis. Vascular corrosion casts of livers belonging to the following three experimental groups were studied by scanning electron microscopy: normal rats, CCl(4)-induced cirrhotic rats and cirrhotic rats after ligation of the bile duct. Photomicrographs were taken at a standard magnification; these images were used for the mathematical analysis. Our experimental design found that use of these different analyses reaches an efficiency of over 94%. Our analyses demonstrated a higher complexity of the normal hepatic sinusoidal network in comparison with the cirrhotic network. In particular, the morphological changes were more marked in the animals with bile duct-ligation cirrhosis compared with animals with CCl(4)-induced cirrhosis. The present findings based on fractal and Fourier analysis could increase our understanding of the pathophysiological alterations of the liver, and may have a diagnostic value in future clinical research.

This work investigated the origin and development of microcirculation in the rat humeral head and the expression of vascular endothelial growth factor (VEGF) as a factor supporting the vascular growth and the development of the secondary ossification centers. Sixty rats aging 1, 3-4, 6-8, 11, and 21 days, 5 weeks, and 4 and 8 months were used. Samples of humeral head were collected for histolgy and immunohistochemistry for VEGF. Some animals were perfused with Mercox resin in order to obtain vascular corrosion casts (vcc) observed by scanning electron microscopy (SEM). No cartilage canals were present at birth. At 6 days postnatal, blood vessels coming from the perichondrium and the region near the capsule attachment invaded the cartilage; at 11 days postnatal, signs of calcification were present and within the third week some bone trabeculae were formed. Just before the vascular invasion of the epiphysis, a positive reaction for VEGF was localized in chondrocytes of the epiphyseal cartilage close to the capsule insertion. During the development and expansion of the secondary ossification center, VEGF expression was higher in chondrocytes but decreased when epiphysis was diffusely ossified. VEGF was expressed also by mesenchymal cells present in and around the fibrous tissue where the secondary ossification center will develop. SEM vcc confirmed that vessels penetrating into the epiphysis arose merely from the periosteal and the capsular networks, and vascular connections with the diaphyseal circulation were not evident. These observations demonstrated that VEGF production by chondrocytes begun some days after birth, supported the rapid vascular growth from the surrounding soft tissues, and was chronologically related to the development of the secondary ossification center in rat proximal humerus. Finally, the possible role of VEGF as mediator of angiogenesis and, at least indirectly, as a trigger factor also in the ossification and the bone remodeling of the secondary ossification centers has been discussed. (C) 2004 Wiley-Liss, Inc.

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.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.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, 0.0065P0.0155; T, P=0.00005; G x T, P=0.00005). High stimulation rate during hypoxia worsened hypoxia-reoxygenation contractile changes, whereas reversibility after dobutamine was less. In both B and C groups during hypoxia, contractility decreased quite rapidly, although by 10 min or so a plateau (approximately 50%) was reached in group B, whereas in group C contractility decreased to20%. None of the covariates contributed significantly to predict the dependent variables investigated. Force-frequency relationship and post-pausal potentiation were repeatable, paralleled overall changes due to hypoxia, reoxygenation and dobutamine challenge and were useful to discriminate Ca2+-related diastolic processes thus helping index myocardial contractile reserve. Force-frequency relationship was negative at high stimulation rates, concomitant to an abrupt change of shape and duration of action potential with little time for Ca2+-related Ca2+ release and ensuing systolic processes. Felodipine pretreatment enabled an unblunted response to dobutamine. Histomorphometry showed an unexpected 'fibrotic core'. At electron microscopy, subendocardial and deep part of the same pectinate muscles showed identical degrees of degenerative lesions. Superfused samples showed, unexpectedly, less anoxic lesions than preparations fixed within 15 min from surgical explant, although lesions were higher than in samples fixed immediately after explant.This might be a relevant model, whereby pharmacological or physical interventions are tested. Native human atrial trabeculae might be used without dissection and/or preservatives. If high stimulation rate during hypoxia is used the power of hypothesis testing is maximized. Future studies with this material will be easier and comparatively smaller series might be investigated. Felo

Purpose: The aim of the present preliminary study, performed on post-surgical hypotony, was the evaluation of the effects on ocular hypotony of the concomitant administration of ibopamine and corticosteroids. Methods: 14 patients (11 males — 3 females; mean age 47 years) with ocular hypotony following several vitroretinal surgical intervention in different districts, were enrolled. The inclusion criteria were: mean IOP during tonometric curve equal or lower than 6 mmHg, stable IOP for at least 60 days, ongoing treatment with 0.1% dexamethasone (4 times/day), successful surgical intervention, 2% ibopamine (4 times/day) was added to the corticosteroid therapy for 30–60 days. Results: Before ibopamine administration, mean IOP was 4.07 mmHg SD 1.71. At the end of the treatment period, mean IOP increased by 89% in comparison to baseline values (+ 3.64 mmHg SD 5.57). This difference was statistically significant (paired t = 2.39; P = 0.03). One month after ibopamine-treatment discontinuation, mean IOP decreased to pre-treatment values (4.86 mmHg SD 3.50). Conclusions: The results of the present study, although preliminary, suggest the possibility of a future pharmacological treatment of ocular hypotony with ibopamine, whose rationale is based on the increase of aqueous humor production by stimulating the D1 dopaminergic receptor.

In Retinitis Pigmentosa the progressive photoreceptor degeneration determines severe functional loss and visual impairment and consequently retinal sensitivity damage.

Retinitis Pigmentosa (RP) is a group of inherited progressive degenerative disorders of the retina genetically transmitted by recessive X-linked, recessive autosomal, dominant autosomal or digenic inheritance patterns.

During the past few years, different approaches to the study of pericytes in the skeletal muscle microvasculature have been made through the use of different techniques, including corrosion casts.

Rabbit peritoneum was studied by SEM to obtain information and statistically meaningful morphometric data of different sites of visceral and parietal peritoneum and to verify the existence of "stomata." Samples were fixed by intraperitoneal infusion of glutaraldehyde, and were photographed by SEM under standard conditions. Morphometric data were obtained by Kontron MOP Videoplan. Variable cell surface patterns were present even within limited areas; however, "stomata" were not observed. The heterogeneity of data obtained can be related to the dynamism of mesothelial cell activity and to the different motilities of the underlying organs.

The microvascular supply of the biliary tree, the peribiliary plexus (PBP), stems from the hepatic artery branches and flows into the hepatic sinusoids. A detailed three-dimensional study of the PBP has been performed by using the Scanning Electron Microscopy vascular corrosion casts (SEMvcc) technique. Considering that the PBP plays a fundamental role in supporting the secretory and absorptive functions of the biliary epithelium, their organization in either normalcy and pathology is explored. The normal liver shows the PBP arranged around extra- and intrahepatic biliary tree. In the small portal tract PBP was characterized by a single layer of capillaries which progressively continued with the extrahepatic PBP where it showed a more complex vascular network. After common duct ligation (BDL), progressive modifications of bile duct and PBP proliferation are observed. The PBP presents a three-dimensional network arranged around many bile ducts and appears as bundles of vessels, composed by capillaries of homogeneous diameter with a typical round mesh structure. The PBP network is easily distinguishable from the sinusoidal network which appears normal. Considering the enormous extension of the PBP during BDL, the possible role played by the Vascular Endothelial Growth Factor (VEGF) is evaluated. VEGF-A, VEGF-C and their related receptors appeared highly immunopositive in proliferating cholangiocytes of BDL rats. The administration of anti-VEGF-A or anti-VEGF-C antibodies to BDL rats as well as hepatic artery ligation induced a reduced bile duct mass. The administration of rVEGF-A to BDL hepatic artery ligated rats prevented the decrease of cholangiocyte proliferation and VEGF-A expression as compared to BDL control rats. These data suggest the role of arterial blood supply of the biliary tree in conditions of cholangiocyte proliferation, such as it occurs during chronic cholestasis. On the other hand, the role played by VEGF as a tool of cross-talk between cholangiocytes and PBP endothelial cells suggests that manipulation of VEGF release and function could represent a therapeutic strategy for human pathological conditions characterized by damage of hepatic artery or the biliary tree.

The superficial morphology of the pleura has been observed in humans by scanning electron microscopy (SEM). Pleural samples from the visceral, mediastinal, diaphragmatic and costal normal human pleura were observed, and a thorough morphometric study was performed. The most evident feature was the ubiquitous presence of microvilli and micropores. The secretion and absorption activities therefore should not be regarded as accomplished by different topographic zones of the pleura. Discontinuities and clefts were observed at the level of cellular junctions; absorption of high weight molecules and cells from the pleural space may be facilitated at this level, but the structures which were observed in humans may not be considered "stomata," according to the definition of such morphologic units as we give in the present study. Cilia and blebs, described in the experimental animal or in other mesothelia, were not seen in the human pleura.

The authors used a microcorrosion cast technique to study the microvascular bed of skeletal muscles in the rat. They also tried to clarify the differences, in this respect, between fast twitch and slow twitch muscles. For this purpose they studied as fast twitch muscles, the tibialis anterior muscle and the pectineus muscle and, as a slow twitch mus cle, the soleus muscle. Thanks to the peculiar technique used, they were able to distinguish differ ent sections of the microvascular bed. They also found astonishing differences between the capillary networks in the soleus and tibialis anterior muscles, on the original bases of peculiar charac teristics of the capillary network in the soleus.

The authors used the microcorrosion cast technique to study the localization and the role of pericytes in the microcirculation of skeletal muscle. Both fast twitch muscles, the tibialis anterior and the pectineus muscles, and a slow twitch one, the soleus muscle, were studied, because of morphological differences of their capillary networks. The observation of peculiar imprints on the surface of vascular casts, strate gically sited in the microvascular bed, were related to the presence of pericytes apposed to the endothelial lining. The role of pericytes in adeguating the local blood flow to metabolic needs and in maintaining capillary blood flow despite pinching of vessels is discussed.

The morphology of the retinal microcirculation has been extensively studied by different techniques. Nevertheless, some problems concerning the capillary bed lamination and pre- and postcapillary patterns have not yet been clarified. In the present study the SEM corrosion cast technique was employed to study the three-dimensional relationships of rat retinal vessels and to follow the smallest vascular branches. Rat retina is considered a useful experimental model for a number of pathologies which affect the microvascular bed deeply. Two precapillary patterns have been observed. Precapillary arterioles gave rise to capillaries both as terminal branches or as collaterals. The former pattern of ramification allows only a regulation of flow in a whole group of capillaries downstream, the latter pattern could provide a finer regulation of blood flow. SEM corrosion casts have shown very well the lamination of the capillary bed: one can easily realize this by seeing the overlapped meshes of the two different planes, vessels in between the two capillary laminae can always be followed from one meshwork to the other. This three-dimensional organization is an interesting model for retinal circulation because it shows many features in common with the retina of humans and primates

The authors studied the correlations between electroretinographic, ophthalmologic, and clinical parameters in 30 pregnant women (20 with diabetes and 10 control subjects). Diabetic patients were divided into two groups: group 1 included 11 cases of insulin-dependent diabetes (IDDM); and group 2 included 6 cases of noninsulin-dependent diabetes (NIDDM) and 3 cases of gestational diabetes (GDM). Adapto-electroretinography (AERG) was used as the main monitoring parameter, and in particular, the relationship between the cone-mediated (b1) and rod-mediated (b2) components of the b wave (b2/b1 ratio) 7 minutes after photobleaching was studied. The results indicate that the b2/b1 ratio can detect functional modifications before the onset of ophthalmoscopically detectable retinopathy. Significant statistical correlations were demonstrated both between the type of diabetes and AERG responses, and between metabolic control (HbA1c values) and AERG alterations. A higher maternofetal complication rate in those patients with severe and frequent AERG alterations during pregnancy also was found.