Cannabinoid agonist WIN55,212 in vitro inhibits interleukin-6 (IL-6) and monocyte chemo-attractant protein-1 (MCP-1) release by rat pancreatic acini and in vivo induces dual effects on the course of acute pancreatitis.

BACKGROUND: Cannabinoids (CBs) evoke their effects by activating the cannabinoid receptor subtypes CB1-r and CB2-r and exert anti-inflammatory effects altering chemokine and cytokine expression. Various cytokines and chemokines are produced and released by rodent pancreatic acini in acute pancreatitis. Although CB1-r and CB2-r expressed in rat exocrine pancreatic acinar cells do not modulate digestive enzyme release, whether they modulate inflammatory mediators remains unclear. We investigated the CB-r system role on exocrine pancreas in unstimulated conditions and during acute pancreatitis. METHODS: We evaluated in vitro and in vivo changes induced by WIN55,212 on the inflammatory variables amylasemia, pancreatic edema and morphology, and on acinar release and content of the cytokine interleukin-6 (IL-6) and chemokine monocyte chemo-attractant protein-1 (MCP-1) in untreated rats and rats with caerulein (CK)-induced pancreatitis. KEY RESULTS: In the in vitro experiments, WIN55,212 (10(-6) mol L(-1)) inhibited IL-6 and MCP-1 release from acinar cells of unstimulated rats and after CK-induced pancreatitis. In vivo, when rats were pretreated with WIN55,212 (2 mg kg(-1), intraperitoneally) before experimentally-induced pancreatitis, serum amylase, pancreatic edema and IL-6 and MCP-1 acinar content diminished and pancreatic morphology improved. Conversely, when rats with experimentally-induced pancreatitis were post-treated with WIN55,212, pancreatitis worsened. CONCLUSIONS & INFERENCES: These findings provide new evidence showing that the pancreatic CB1-r/CB2-r system modulates pro-inflammatory factor levels in rat exocrine pancreatic acinar cells. The dual, time-dependent WIN55,212-induced changes in the development and course of acute pancreatitis support the idea that the role of the endogenous CB receptor system differs according to the local inflammatory status.

An overview on immune system and migraine.

The pathogenesis of migraine is still unclear, but much evidence led us hypothesize that it can be associated with immune system modification, so that a role for cytokines has been suggested. Cytokines are important mediators of the immune and inflammatory pathways and their receptors are widely express in central nervous system (CNS) by all cell types, including neurons, indicating that they can act on neuronal receptors. Cytokines are now considered to be the pain mediators in neurovascular inflammation. Furthermore cytokines may be a cause of the migraine pain: in fact an high levels of chemokines could stimulate the activation of trigeminal nerves, the release of vasoactive peptides or other biochemical mediators, such as nitric oxide, and then to cause inflammation. In this scenario, many studies on humans have focused the attention on peripheral and central levels of cytokines, but data obtained are highly controversial. Since at the moment there is not a conclusive evidence of the role played by cytokines in migraine, the authors present and comment the latest reports regarding cytokine modification and the role of the immune system in migraine.

Angiosarcoma of the heart: structural and ultrastructural study.

BACKGROUND: Primary cardiac tumours are rare. Nearly 70% of primary cardiac tumours are benign, the majority of which are represented by myxomas. The most frequent primary cardiac neoplasm is the angiosarcoma that represents 31% of primary cardiac malignant. We report a particular clinical case of cardiac angiosarcoma, its light and transmission electron microscopic aspects and a review of the recent literature. METHODS: A 52 years old man died for a severe right ventricle filling deficit caused by an intracavitary tumour originated from the right atrial anterolateral wall. The fragments obtained from autoptic tumoral cardiac tissue were processed for light and electron microscopy. The section were stained with haematoxilineosin, Masson trichromic and Gomori method. An immunohistochemical study for vimentin, Factor VIII related antigen and peroxidase-conjugated lectin from Ulex Europaeus was also performed using the unlabed peroxidase-antiperoxidase method. RESULTS: The hematoxylin-eosin staining showed that the tumoral mass was composed by a well-differentiated histotype characterized by numerous vascular areas in which neoplastic cells were loosely and irregularly arranged to form incomplete vessels or anastomized blood-filled vascular channels. On the other hand, some less-differentiated solid areas were present and irregularly surrounded the differentiated vascular areas. Results of Ulex Europeaeus Agglutinin I labelling were positive in both solid and vascular areas of the tumour although the positive reaction was less evident in the solid zones Factor VIII related antigen positive cells were less numerous and mainly found in vascular areas. The observation by electron microscopy showed the lack of evident pinocytotic vesicles, the presence of thin and delicate cytoplasmatic processes, Weibel-Palade bodies, and also the disarrangement of the extracellular fibrous matrix. CONCLUSION: The light microscopy observation and immunohistochemical study underscore that is not easy to obtain information about the level of differentiation of this tumour. The presence of blood-filled lumina and the identification of typical markers of endothelial cells seems to indicate a well-differentiated nature. However, the ultrastructural findings seem to indicate a less differentiated nature.

[Intraoperative limphonodal mapping in gastric, pulmonary and large bowel tumors. The sentinel limphonode technique]. / Mappatura linfonodale intraoperatoria in tumori gastrici, polmonari e del grosso intestino. La tecnica del linfonodo sentinella.

The concept of the sentinel lymphatic node was introduced by Cabanas in 1977, but it has proved to be successful for the treatment of the melanoma and breast cancer only since the 90s. Many studies have recently extended this technique to other neoplasias. This study deals with 36 patients who were to undergo surgery for 14 gastric adenocarcinomas, 11 of the colon and 11 pulmonary. Once the neoplastic mass was detected, 2 to 5 ml of a vital dye (Blu Patent) were injected in the serosa along the perimeter of the tumor by means of several 0.5 ml injections. A lymphatic node was diagnosed in 22 patients, respectively 10 gastric neoplasias, 6 pulmonary, 6 of the colon. In 14 cases the lymphatic node was found to be negative, in 8 cases positive. In the remaining 14 patients the lymphatic node was not detected. Although data do not always agree, the sentinel lymphatic node technique seems to have been successful for this kind of tumors. For this reason we have carried out this study and published our first data.

Usefulness of endoscopic small intestinal biopsies in children with coeliac disease.

Small intestinal biopsy is the most important diagnostic method in the routine evaluation of children with chronic diarrhoea and malabsorption. At present morphological alterations are considered essential in the diagnosis of coeliac disease (CD) and the presence of a normal small bowel biopsy specimen, observed in patients eating a diet containing gluten, rules out the diagnosis of CD. The small intestinal biopsy can be carried out either by blind suction capsule or by endoscopic forceps. In everyday clinical practice endoscopic duodenal biopsies, if taken and handled suitably, are accepted as equivalent to capsule biopsies from the proximal jejunum. In the study we reported some patients in whom has been possible to demonstrate the presence of total villous atrophy in one biopsy, while other duodenal samples taken in different duodenal portions were normal or showed mild lymphocytes and plasmacells infiltrations of the lamina propria. In patients with this type of biopsy pathology, wherein flat mucosa has been found even close to normal mucosa, the possible explanation is mucosal patchiness. The occurrence of patchly distributed intestinal atrophy in children suffering of CD raises the question of the validity of using the peroral capsule, widely believed to be the best standard for the diagnosis of CD. In our opinion, small intestinal biopsies obtained via endoscopy are more reliable than the peroral capsule biopsies in order to identify patchy mucosal atrophy and could be very useful for a correct diagnosis in CD patients.

[Non-Hodgkin's lymphoma in multiple places and uterine involvement]. / Linfoma non-Hodgkin a localizzazioni multiple con interessamento uterino.

Multiple locations of non-Hodgkin lymphoma, in cases of recurrence of disease, may affect all the lymph node stations. The case reported, sited in the uterus, constitutes a very rare event and whenever it occurs the preoperative diagnosis may present serious difficulties. Surgery, which must be prompt and radical, is mandatory for histopathological staging of the disease and for the implementation of an appropriate chemotherapy protocol. In the case reported here the diagnostic work-up enabled us to achieve correct preoperative staging.

Helicobacter pylori duodenal colonization in children.

To investigate the prevalence and the significance of Helicobacter pylori duodenal colonization, endoscopic duodenal biopsies were performed in 168 children with chronic abdominal pain, gastroesophageal reflux, gastrointestinal bleeding, and malabsorption syndrome. Helicobacter pylori infection was detected in 68 children (40.4%): in 31 of them H. pylori was present in the gastric antrum, and in 37 in the duodenum also. Duodenitis was observed in 25 children with duodenal H. pylori; gastric metaplasia in 3. Scanning electron microscopy revealed the presence of the micro-organism in 3/13 cases; the bacteria were located in the intercellular spaces and alterations of the epithelial surface were found. In conclusion, H. pylori gastritis in children is often associated with duodenal colonization which can cause duodenitis, and also without gastric metaplasia, which indicates a possible role of the micro-organism in the pathogenesis of the lesions.

A new morphological classification during follow-up in patients with celiac disease: a three-dimensional observation by scanning electron microscopy.

The structure and ultrastructure of the villi of small intestinal mucosa was examined in 237 duodenal or jejunal biopsies taken from children with active celiac disease and during gluten-free diet. All biopsies were processed for light and scanning electron microscopy. Conventional histology showed four different morphological aspects: total and subtotal villous atrophy in patients on unrestricted diet, partial villous atrophy and normal mucosa during gluten-free diet. Scanning electron microscopy demonstrated that in active celiac disease the severity of the intestinal lesions was related to individual vulnerability to gluten. Our results showed that during dietary treatment the process of mucosal healing was constant and strictly time-dependent. Furthermore, the ultrastructural examination has been relevant in evaluating the evolution of the villous regeneration. In this study a classification regarding the healing process of the small intestinal mucosa correlated with the time of start of dietary therapy is proposed.

[High incidence of Helicobacter pylori infections in an endoscopic pediatric patient series]. / Elevata incidenza di infezione da Helicobacter pylori in una casistica endoscopica pediatrica.

We evaluated in children with abdominal complaints the prevalence of Helicobacter pylori gastric and duodenal colonization and the histological features of gastric and duodenal mucosae. Fifty patients, aged 1-17 years, underwent upper endoscopy for recurrent abdominal pain, vomiting and/or gastrointestinal bleeding. With serological, bacteriological and/or histological methods twenty-eight children were demonstrated to be Helicobacter pylori-positive. No statistically significant differences were observed with regard to age, sex and indication to perform endoscopy. Eighty-two percent of Helicobacter pylori-positive patients had gastritis and/or duodenitis. The Helicobacter pylori-positive children had higher Helicobacter pylori specific IgG levels than the Helicobacter pylori-negative ones (p < 0.001). No statistically significant differences were found between Helicobacter pylori-positive and Helicobacter pylori-negative subjects, for gastrin and pepsinogen I. Since the frequency of Helicobacter pylori infection in children with gastrointestinal complaints is high, in patients undergoing upper endoscopy, the sistematical examination of bioptic samples for bacteriological and histologic procedures is of great importance.

Renal ischemia and pharmacological prevention: experimental structural and ultrastructural observations.

Defibrotide is a polydeoxiribonucleotid derived from the bovine's lung. It stimulates the release of prostacyclines (PGI2) from the vascular endothelium, thus determining profibrinolytic, antithrombotic, and thrombolytic actions. These activities have been experimentally demonstrated by several authors in different animal species through models of ischemia in different organs. The aim of the present study was to carry out an experimental model of acute renal insufficiency with a bilateral and temporal hot ischemia in order to confirm by light microscopy the structural alterations, and by transmission and scanning electron microscopy the ultrastructural alterations, and therefore establish the effects of Defibrotide in preventing reperfusion injuries. Kidney samples were observed as a blind-trial by three different operators. A certain preventive effect against ischemia was evidenced, probably due to the cytoprotective action of Defibrotide in close relation also with an increase in PGI2 production.

Transitional papillary cell carcinoma of the ureter: a histological and ultrastructural study.

We report a case of transitional papillary carcinoma of the distal left ureter. The histological and ultrastructural features were seen and compared by SEM and TEM. Observations confirm the data of literature that the deep cells of neoplasm are a normal morphological finding while the superficial cells do not have the characteristics present in normal transitional cells. In addition, SEM shows small groups or single cells with "pleomorphic microvilli" on the cell surface. These, in ureter, confirm the studies of many authors who have observed these abnormalities in carcinomas of several organs like breast, colon, liver and mesothelium.

[Asymptomatic peritoneal endometriosis following cesarean section]. / Endometriosi peritoneale asintomatica dopo taglio cesareo.

Endometriotic peritoneal implants of small dimensions were discovered in five patients undergoing laparoscopic examination for diseases unrelated to endometriosis. All patients were asymptomatic for endometriosis and each had undergone at least one previous cesarean section. Biopsies taken were studied by light microscopy which evidenced variably predominating epithelial or stromal components of lesions Perls' method was used to evidence tissue ferric iron resulting from long-standing micro-haemorrhagic foci. From this study, isolated, asymptomatic peritoneal implants of endometrium are suspected to occur frequently after cesarean section although the progression of this condition to a symptomatic state is considered infrequent and independent of specific histologic aspects of lesions.

Cytoprotective drugs in the prevention of ethanol-induced experimental gastric mucosal damage: a morphological study.

Various so-called "cytoprotective" agents (sucralfate, carbenoxolone, 16,16-dimethyl-PGE2, sulglycotide and Maalox TC) have been tested on rats, with the aim of quantifying their capability to prevent ethanol-induced gastric mucosal damage. Rats fasted for 48 hours received 1 ml of 80% ethanol by oral gavage, after prior oral treatment with placebo or one of the above-mentioned drugs u.i.d. for 5 consecutive days. Six hours after ethanol administration, the animals were sacrificed and the stomach was removed and processed for computerized macroscopic assessment of the damaged surface and for structural (light microscopy) and ultrastructural (scanning and transmission electron microscopy) studies. The results obtained demonstrate that ethanol injury caused extensive mucosal necrosis of the glandular region of the stomach, an event that was effectively reduced in rats treated with 16,16-dm-PGE2, carbenoxolone or sulglycotide. These drugs appeared to preserve the mucosa, with morphology comparable to that of normal noninjured rats - in contrast to the other drugs investigated. These data confirm the cytoprotective properties of sulglycotide in particular, which was the most potent agent for preventing the development of ethanol-induced acute lesions of the gastric mucosa.

Influence of labour on epidermal growth factor receptor distribution of the human chorion at term gestation.

Chorion was obtained from 10 healthy pregnant women at term gestation who were delivered either vaginally (n = 5) or by elective repeat caesarean section before the onset of labour (n = 5). Epidermal growth factor (EGF) receptors in chorionic tissue were evaluated by means of freeze fracture technique (label fracture). They were found to be significantly less, but more frequently coupled, in specimens obtained after labour than before the onset of labour. These findings suggest that a functional activation of EGF receptors in human chorion might occur during labour.

Preliminary results of a complete study protocol on synthetic vascular graft healing and its complications.

The microscopic and anatomic features and bacteriologic culture results of different portions of single, explanted dacron synthetic vascular grafts (SVG) were studied together with patient clinical data. With this complete study protocol a better understanding of the healing process and its associated pathology can be achieved. We studied three, amply distanced graft portions from each of five patients (15 total graft portions) undergoing revision for infectious and non-infectious reasons. We divided the SVG portions studied into a Group 1, with high degrees of graft healing and into a Group 2, with both infection-dependent, early healing complications and perigraft chronic inflammatory reaction-dependent, late healing complications. These late healing complications were found dependent upon a host vs graft reaction. This study confirmed in humans the important role of an internal and external fibrotic graft incorporation in the definitive healing of a SVG. A host vs graft reaction was suggested to be an alternative to the frequently cited low virulent infection pathogenesis of late SVG healing complications. A sure definition and treatment of late SVG healing complications will only be established by means of a complete study protocol performed on a large number of explanted SVGs.

Scanning electron microscopy of the small intestine during gluten-challenge in celiac disease.

The celiac disease syndrome is characterized by structural and ultrastructural alterations of the small intestine mucosa. According to criteria by European Society of Paediatric Gastroenterology and Nutrition, the conclusive diagnosis of celiac disease in children depends on the demonstration of histological relapse of the mucosa after reintroduction of gluten in the diet, as this syndrome is a permanent condition of gluten intolerance. Under these diseased conditions, the structure of the intestinal villi has been studied by light microscopy; morphological alterations were revealed only when the gluten challenge induced a clinical relapse. Scanning electron microscopy analyses of the intestinal mucosa in celiac diseased patients showed a strikingly uniform destruction of the villi with changes in their dimensions and arrangement. At high magnification the enterocytes were irregular in size and shape with a decrease and disruption of the glycocalyx. Reductions in length and density of microvilli were also clearly identified. Although these scanning electron microscopy findings could not demonstrate a relationship between the degrees of mucosal atrophy and the duration of the gluten challenge, they nevertheless revealed early stages of fine villous alterations that cannot be detected by the presently employed low resolution light microscopic techniques.

Scanning electron microscopy observations of nasal mucosa in patients affected by retinitis pigmentosa.

A controlled study of the ciliated epithelium of olfactory mucosa was performed on 25 patients affected by retinitis pigmentosa and in 5 healthy subjects. Scanning Electron Microscopy showed a significant lack of ciliated epithelial cells. These cells probably represent undifferentiated ciliated cells. These morphological alterations of the olfactory mucosa might correspond to similar changes in the outer segment of retinal photoreceptors in retinitis pigmentosa.

Expression of class II MHC antigens in the intestinal epithelium of pediatric celiac disease.

Class II MHC antigen expression in the intestinal epithelium of 28 small bowel biopsies from 23 celiac patients were studied by means of indirect immunofluorescence and immunoperoxidase using monoclonal antibodies. Patients were divided on the basis of diet into two subgroups: 15 subjects on a gluten-containing diet (GCD) and 13 on a gluten-free diet (GFD). The control group included 10 pediatric subjects with normal intestinal mucosa who underwent intestinal biopsy for chronic diarrhea or short stature. DR antigens and invariant chain were expressed in all patients, regardless of the diet, as well as in the control subjects. DQ was found in one patient only on GCD. DP antigens were present in 12/15 patients on GCD, and in 2/13 on GFD (Fisher's exact test, p = 8.8 x 10(-4), as well as in 3/10 control subjects. In 4/5 celiac patients, DP antigens, which were undetectable on GFD, could be demonstrated after gluten challenge. The results of the study show that DR antigens are expressed by intestinal mucosa of celiac patients independently of their gluten exposure and that DQ antigens are consistently undetectable. Statistically significant differences in expression of DP antigens on enterocytes of celiac patients on GCD and their neoexpression after gluten challenge may represent a basis for further investigation.

Distribution and effect on the endometrium of progesterone released from a progestasert device.

Progestasert devices releasing 65 micrograms of [14C]progesterone daily were inserted in 10 women 3 months prior to elective hysterectomy. Following surgery, specimens were examined by light and electron microscopy and by autoradiography. In three uteri, removed during the early follicular phase, there was a clear contrast between the appearance of the superficial portion of the endometrium in the zone immediately adjacent to the device, when compared to areas away from the progestasert. This difference became more pronounced in four specimens obtained at mid-cycle and tended to diminish during the luteal phase: the number of glands was still lower than normal, but stromal decidual reaction was apparent throughout the functional layer of endometrium; in addition, in portions away from the device, glands showed the characteristics of a secretory phase. Progesterone and/or its metabolites were abundant in the superficial epithelium and in the portion of the glands adjacent to the surface; and also well distributed in the stroma and in the capillary walls. Historadiography however, clearly showed that progesterone barely penetrated the deeper portion of the endometrium. This picture does not substantially change during the entire cycle.