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Supplemental Material, Giubilato_coi_disclosure for The Combination of Oral Anticoagulant and Antiplatelet Therapies: Stay One Step Ahead by Fabiana Lucà, Simona Giubilato, Stefania Angela Di Fusco, Angelo Leone, Stefano Poli, Carmelo Massimiliano Rao, Annamaria Iorio, Sandro Gelsomino, Domenico Gabrielli, Furio Colivicchi, Leonardo De Luca and Michele Massimo Gulizia in Journal of Cardiovascular Pharmacology and Therapeutics

Supplemental Material, De_Luca_disclosure for The Combination of Oral Anticoagulant and Antiplatelet Therapies: Stay One Step Ahead by Fabiana Lucà, Simona Giubilato, Stefania Angela Di Fusco, Angelo Leone, Stefano Poli, Carmelo Massimiliano Rao, Annamaria Iorio, Sandro Gelsomino, Domenico Gabrielli, Furio Colivicchi, Leonardo De Luca and Michele Massimo Gulizia in Journal of Cardiovascular Pharmacology and Therapeutics

Supplemental Material, Luca_coi_disclosure for The Combination of Oral Anticoagulant and Antiplatelet Therapies: Stay One Step Ahead by Fabiana Lucà, Simona Giubilato, Stefania Angela Di Fusco, Angelo Leone, Stefano Poli, Carmelo Massimiliano Rao, Annamaria Iorio, Sandro Gelsomino, Domenico Gabrielli, Furio Colivicchi, Leonardo De Luca and Michele Massimo Gulizia in Journal of Cardiovascular Pharmacology and Therapeutics

Supplemental Material, Colivicchi_disclosure for The Combination of Oral Anticoagulant and Antiplatelet Therapies: Stay One Step Ahead by Fabiana Lucà, Simona Giubilato, Stefania Angela Di Fusco, Angelo Leone, Stefano Poli, Carmelo Massimiliano Rao, Annamaria Iorio, Sandro Gelsomino, Domenico Gabrielli, Furio Colivicchi, Leonardo De Luca and Michele Massimo Gulizia in Journal of Cardiovascular Pharmacology and Therapeutics

Supplemental Material, Gulizia_disclosure for The Combination of Oral Anticoagulant and Antiplatelet Therapies: Stay One Step Ahead by Fabiana Lucà, Simona Giubilato, Stefania Angela Di Fusco, Angelo Leone, Stefano Poli, Carmelo Massimiliano Rao, Annamaria Iorio, Sandro Gelsomino, Domenico Gabrielli, Furio Colivicchi, Leonardo De Luca and Michele Massimo Gulizia in Journal of Cardiovascular Pharmacology and Therapeutics

Supplemental Material, Leone_disclosure for The Combination of Oral Anticoagulant and Antiplatelet Therapies: Stay One Step Ahead by Fabiana Lucà, Simona Giubilato, Stefania Angela Di Fusco, Angelo Leone, Stefano Poli, Carmelo Massimiliano Rao, Annamaria Iorio, Sandro Gelsomino, Domenico Gabrielli, Furio Colivicchi, Leonardo De Luca and Michele Massimo Gulizia in Journal of Cardiovascular Pharmacology and Therapeutics

Supplemental Material, Gabrielli_disclosure for The Combination of Oral Anticoagulant and Antiplatelet Therapies: Stay One Step Ahead by Fabiana Lucà, Simona Giubilato, Stefania Angela Di Fusco, Angelo Leone, Stefano Poli, Carmelo Massimiliano Rao, Annamaria Iorio, Sandro Gelsomino, Domenico Gabrielli, Furio Colivicchi, Leonardo De Luca and Michele Massimo Gulizia in Journal of Cardiovascular Pharmacology and Therapeutics

Supplemental Material, Gelsomino_disclosure for The Combination of Oral Anticoagulant and Antiplatelet Therapies: Stay One Step Ahead by Fabiana Lucà, Simona Giubilato, Stefania Angela Di Fusco, Angelo Leone, Stefano Poli, Carmelo Massimiliano Rao, Annamaria Iorio, Sandro Gelsomino, Domenico Gabrielli, Furio Colivicchi, Leonardo De Luca and Michele Massimo Gulizia in Journal of Cardiovascular Pharmacology and Therapeutics

Supplemental Material, Poli_disclosure for The Combination of Oral Anticoagulant and Antiplatelet Therapies: Stay One Step Ahead by Fabiana Lucà, Simona Giubilato, Stefania Angela Di Fusco, Angelo Leone, Stefano Poli, Carmelo Massimiliano Rao, Annamaria Iorio, Sandro Gelsomino, Domenico Gabrielli, Furio Colivicchi, Leonardo De Luca and Michele Massimo Gulizia in Journal of Cardiovascular Pharmacology and Therapeutics

Supplemental Material, Rao_disclosure for The Combination of Oral Anticoagulant and Antiplatelet Therapies: Stay One Step Ahead by Fabiana Lucà, Simona Giubilato, Stefania Angela Di Fusco, Angelo Leone, Stefano Poli, Carmelo Massimiliano Rao, Annamaria Iorio, Sandro Gelsomino, Domenico Gabrielli, Furio Colivicchi, Leonardo De Luca and Michele Massimo Gulizia in Journal of Cardiovascular Pharmacology and Therapeutics

Supplemental Material, Di_Fusco_disclosure for The Combination of Oral Anticoagulant and Antiplatelet Therapies: Stay One Step Ahead by Fabiana Lucà, Simona Giubilato, Stefania Angela Di Fusco, Angelo Leone, Stefano Poli, Carmelo Massimiliano Rao, Annamaria Iorio, Sandro Gelsomino, Domenico Gabrielli, Furio Colivicchi, Leonardo De Luca and Michele Massimo Gulizia in Journal of Cardiovascular Pharmacology and Therapeutics

Supplemental Material, Iorio_disclosure for The Combination of Oral Anticoagulant and Antiplatelet Therapies: Stay One Step Ahead by Fabiana Lucà, Simona Giubilato, Stefania Angela Di Fusco, Angelo Leone, Stefano Poli, Carmelo Massimiliano Rao, Annamaria Iorio, Sandro Gelsomino, Domenico Gabrielli, Furio Colivicchi, Leonardo De Luca and Michele Massimo Gulizia in Journal of Cardiovascular Pharmacology and Therapeutics

International audience; Correction Figure 4: Prototype of tumors upon sacrifice, formed in non-diabetic and diabetic mice treated with rapamycin, metformin and their combination with probiotics. Note the difference in tumor size in the different groups; animals from groups 4B and 8B treated with rapamycin and metformin in combination with probiotics had significantly smaller tumor size when compared to groups treated with Met alone, rapamycin alone or untreated animals.

The involvement of intestinal microbiota and dysbiosis in the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC) is a well-established fact to be taken into real consideration when developing tartgeted therapies. This review aimed to depict what advances in our understanding of the role of intestinal flora in the pathogenesis of IBD and CRC is shaping up the therapeutic protocols of their management. It was demonstrated that there is a circadian regulation of colocytes gene expression in response to microbiota. In addition, dysbiosis leading to a decrease in microbiome biodiversity was also described in IBD patients whereby thick layers of adherent mucosa associated bacteria exist both in ulcerative colitis (UC) and Crohn's disease (CD). Probiotics based approaches using lactobacilli and Bibidobacteria improved clinical symptoms of IBD's through the GALT immune modulation. In addition, fecal microbiota transplantation (FMT) has also been used for IBD treatment. It consists of transferring gastrointestinal microbiota from a healthy donor to an IBD patient by duodenal infusion of liquid stool suspension to establish microbial homeostasis. The passage of bacteria in the injured mucosal zone triggers chronic inflammation and eventually CRC development by creating a carcinogenic environment. Actually, high level of Fusobacterium nucleatun and other bacteria are prevalent in CRC patients, thus suggesting a potential role of these organisms in the initiation and progression processes due to the production of genotoxic metabolites causing a direct damage to DNA integrity. Moreover, regular probiotics intake was shown to actively prevent the whole process. In conclusion, the mutualistic relationship between microbiota and colonic mucosa proved useful in depicting some of the dynamics of the initiation and development of IBD and CRC. Therapies oriented towards establishing equilibrium of intestinal microbiota may represent the key strategy to switch off chronic inflammatory processes hitting colonic mucosa, thus preventing the onset of CRC.

Background: Nutraceuticals provide added health benefits for inflammatory bowel disese (IBD) and Epigallocatechin-3-galate (EGCG), a green tea catechin, has been shown to possess such anti-inflammatory and anti-oxidant effects. Aim: To evaluate the molecular modulation of Reactive Oxygen Species (ROS), Tumor Necrosis Factor-alpha (TNF_alpha), nuclear factor Kappa Beta (NF-Kbeta), Interleukin 6 (IL-6) by EGCG on experimental colitis. Matherial and Methods: Thirthy five male sprague-dawley rats were randomly divided into 4 groups: Normal control group (n=5), EGCG group (n=9), TNBS group (n=9), and TNBS + EGCG group (n=12). For both TNBS and EGCG treated groups, 1 mg/Kg EGCG was administered daily by intraperitoneal injection, starting one week before the induction. at days 3, 10, and 17, rats were sacrificed and the descending colon was collected. The mRNA expressions of IL-6, TNF-alpha and NF-KB were measured by the polymerase chain reaction. In addition, the oxidative stress wasstudied by determination of ROS expression using dihydroethinidine (DHE) staining. results: The results showed that EGCG caused a significant decrease in the mRNA expression of pro-inflammatory cytokines IL-6, TNF-alpha and NF-KB compared to respective non-treated groups. In addition, ROS expression was reduced. Conclusions: These data provide evidence that EGCG is beneficial in TNBS-induced colitis; it exerts an antioxidant activity via decreasing ROS, and an anti-inflammatory effect via ameliorating histological findings and reducing IL-6, TNF-alpha and NF-KB.

Crohn's disease (CD) is a type of inflammatory bowel disease (IBD) and its etiology is multifactorial and involves a combination of genetic environmental factors. The interaction of these factors causes an imbalance of the microbiota, leading to the activation of several immunological and inflammatory mechanism. From an immunological point of view, there seems to be an involvement of the TIM-3/GALECTIN-9 pathway and of the autoregulation of lyTh1. These studies show that in patients with CD the autoregulation of lyth1 is lost due to a reduced concentration of galectin-9 and a reduced TIM-3 expression in LyTh1. This could be one of the reason for the state of perpetual activation of lyTh1, resulting in the chronic inflammation process.

Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, have important extraintestinal manifestations, notably in the oral cavity. These oral manifestations can constitute important clinical clues in the diagnosis and management of IBD, and include changes at the immune and bacterial levels. Aphthous ulcers, pyostomatitis vegetans, cobblestoning and gingivitis are important oral findings frequently observed in IBD patients. Their presentations vary considerably and might be well diagnosed and distinguished from other oral lesions. Infections, drug side effects, deficiencies in some nutrients and many other diseases involved with oral manifestations should also be taken into account. This article discusses the most recent findings on the oral manifestations of IBD with a focus on bacterial modulations and immune changes. It also includes an overview on options for management of the oral lesions of IBD.

DATA FROM LITERATURE ARE CONTROVERSAL REGARDING THE PRESENCE OF bELICOBACTER PYLORI (HP) IN DENTAL PLAQUE AND ITS ASSOCIATION WITH GASTRIC INFECTION. oNE OF THE POSSIBLE MECHANISMS SUGGETSED FOR RE-INFECTION IS THE RECOLONIZATION WITH HP DENTAL PLAQUE. THE PURPOSE OF THIS REVIEW WAS TO DETERMINE WHETHER DENTAL PLAQUE, POOR ORAL HYGIENE, AND PERIODONTAL DISEASE WERE RISK FACTORS FOR HP INFECTION.

The iinate and acquired immune systems are both implicarted in the etiology of Inflammatory Bowel Disease (IBD) in addition to the genetic predisposition, the environmental factors and the intestinal flora covering the mucosa. A defect in the mucous covering will lead to an invasion of pathogens and stimulation of the immuune response with aberrations of mucin 2, the major mucin of the mucous layer. Aim: this study aims to assess the modulation of colonic MUC 2 and MUC 3 in a arat model of IBD induced by a combination of iodoacetamide and enteropatogenic E. Coli. Methods: 78 sprague-Dawley female rats were divided into 4 groups. Each group was subjeceted, on a basis, to a rectal injection of 1% methylcellulose (MC), the veicle, or saturated enteropathogenic E. coli bacterial suspension, or 3% iodoacetamide (IA) in 1% MC, or 3% IA followed by E. Coli infection 48 hours later. Biopsies of the colon were obtained for light microscopy and indirect immunofluorescence using a monoclonal primary antibody MUC 2 and MUC 3. Colonic mucosal scrapings were also use dfor RNA extraction and running for real-time PCR usong MUC 2 and MUC 3 primers. Results: Under light microscopy, the histological sections revealed severe colonic tissue damage in the IA and IA + B groups throughout the experiment. Conclusions: this induuced IBD model succeeded in the arousal and maintanence of IBD for a 2-months period. this inflammation lead to a clear mucosal tissue damage and disruption of the mucosal barrier, togheter with a decreased expression of MUC 2, both on the protein and the RNA levels, whereas MUC 3 expression was not significantly altered.

Nutraceuticals constitute a group of functional foods that provide added health benefits for various disorders including inflammatory bowel disease (IBD) and colorectal cancer (CCR). The main groups of nutraceuticals include probiotics, prebiotics omega 3 and antioxidants. Studies on nutraceutical showed that this type of food possessed similar properties to drugs but with the benefit of not having side effects. This mini review shows that probiotics and prebiotics, when administered simultaneously with traditional therapies, reduce IBD symptoms and reduce synthesis of enzymes probably involved in colorectal carcinogenesis. Moreover, Omega 3 reduces the synthesis of inflammation mediators and prevenents carcinogenesis through interaction interaction with the signaling pathway NOTCH1/MMP9. Moreover, antioxidant reduce the inflammatory process by inhibiting the synthesis of inflammatory mediators, and inhibit the mechanisms of cell proliferation by inducing apoptosis. In brief, nutraceuticals have gained a huge clinical interest since they could be used along with traditional therapy. Bioavailability studies of nutracetical supplements guarantee a correct intake of the substance by oral administration, a matter which would not have been posible to have entirely with the consumprtion of regular food only.

Tooth replantation, as a treatment concept, has been subject to controversies regarding the mechanism as well as the various parameters underlying this process. This work aimed to study time-related changes in the pulp of replanted mature human premolars through the changes in the levels of certain factors involved in the underlying mechanisms of pulpal tissue healing after replantation. Eleven experimental mature teeth were extracted, immediately replanted in the original socket and left without any other intervention for 1, 2, 3 and 12 weeks before re-extraction. Three premolars served as control. All specimens were subject to histological analysis and the levels of MMP-2, MMP-9, Annexin V, iNOS and BCL-2 (anti-apoptotic family) were analyzed employing immunohistochemistry. The results showed degradation of the extracellular matrix (ECM), inflammatory cell infiltrate, loss in pulpo-dentine interface and loss of odontoblasts in the dental pulp tissue. This was accompanied by increase over time of MMP-9, Annexin V, iNOS and a decrease of BCL-2 and MMP-2, suggesting that apoptosis increased throughout the experimental period.

The purpose of this work is to investigate the link between an altered intestinal mcro-biota or dysbiosis and chronic inflammatory disorders, in particular inflammatory bowel disease (IBD). Along with probiotics, faecal microbiota transplantation (FMT) opts to be a promising therapeutic treatment for restoring the bacterial homeostasis of the hu-man intestine and reducing the risk of colorectal carcinogenesis. Microbiota is the com-plex microbial flora that resides in the gut establishing a mutually beneficial relation-ship. Alteration of the microbiota’s composition, termed as dysbiosis, may lead to pathological conditions. Treatment with probiotics can restore the normal commensal flora in IBD. Intestinal microbiota affects the circadian rhythm which in turn regulates the expression of different genes in GALT (gut associated lymphoid tissue) playing a role in the prevention of inflammation and colorectal cancer (CRC) progression. This article highlights the involvement of different microbial strains in the pathogenesis of dysbiosis and in the creation of a carcinogenic milieu caused by an altered stimulation of the immune system. Therapies targeting the equilibrium of the microbiota to switch off chronic inflammation and prevent the progression to CRC seem to be a promising therapeutic tool for a variety of inflammation-associated diseases.

Dental pulp (DP) is a very dynamic tissue both in health and in disease. When exposed to stressors and pathological conditions. It undergoes a complex series of biological reactions whereby alterations affect the pulp tissue at tissue cellular and molecular levels. The aim of this review is to update the reader on the various bio-molecular alterations in the dental pulp under different clinical conditions: orthodontic treatment (OT), caries, pulpitis and others. The morphological changes in the composition of the DP rang from the reversible remodeling to apoptosis and sometimes necrosis. Many apoptotic factors are involved like Bcl2, Bax and the significant increase in Caspases 9 and 3, as well as, Hsp60, its possible role and its mitochodrial localization. The inflammatory responses in dental pulp and the role of diffusible and cellular factors as well as DP stem cells were highlighted, in particular, where caries was involved in the pulpitis.Recent data report changes in tissue metabolism and homeostasis inside the DP caused by OT leading to increased levels of iNOS reactivity in the nerve fibers of the pulp. Moreover, remodeling of the extra cellular matrix(ECM) is an important feature in clinical scenarios like OT and caries whereby alterations in MMP-2 and MMP-9 expression patterns are reported leading to degradation of type IV and V collagens in the ECM. Furthermore, neurogenic factors are also modified after injuries and OT. Neuropeptides play a significant role not onlyin pain perception but also in vascular responses. Substance P increases in DP and enhances pain perception and so is the increase in CGRP which is correlated with concomitant gain in bone morphogenetic protein expression resulting in more dentin formation. The role of stem cells and the possible molecular mechanisms of dentin genesis are presented in this review. They focus on important signaling proteins and the possible role of various scaffolds in this regeneration process. In conclusion, most alterations inpulpal structure are reversible unless the pulp has a history of caries, restorations, trauma or prolonged heavy orthodontic forces. Pulpal symptoms arising from these clinical conditions should be treated appropriately and swiftly.Otherwise, exacerpation of pulpitis and the interplay of the various bio-molecular factors will lead to inhibition of repair and regeneration.

Background and aim: The superior mesenteric artery (SMA) syndrome is a rare entity presenting with upper gastrointestinal tract obstruction and weight loss, due to the compression of the third part of duodenum between the aorta and the SMA. Studies to determine the optimal methods of diagnosis and treatment are essential. This study aims to analyze the clinical presentation, the doagnosis and the management of this syndrome. Material and medthods: Over a 2-year (2013-2014), 8 cases of SMA syndrome (out of 2074 esophago-gastro-duodenoscopies, EGDS) were initially suspected through EGDS. Therefore, these patients performed computed tomography (CT) scan to confirm the diagnosis. Once the diagnosis was confirmed, the patients were referred to a gastroenterologist and to a nutritionist to discuss a personalized approach of therapy; furthermore, for each patient a surgical consultation was proposed. Results: In our series we evaluated retrospectively 8 cases of SMA (6 females), with a prevalence of 0,004%. Median age was 23,5 years (range 14-40), and median weight was 47,5 kilos (range 40-84). the median body mass index was 21 kilos/m2. Symptoms developed between 6 to 24 months (median 12). Premorbid conditions were present in four patients (anorexia nervosa in two patients, spina bifida and Crohn's disease in two patients). Only 2 of 8 patients were hospitalized, due to severe malnutrition. Median aorto-mesenteric angle was 22, and median aorta-SMA distance was 5 mm. Interestingly, all the patients improved on conservative treatment. Conclusions: To date, SMS syndrome represents a diagnostic and therapeutic challenge. With regard to previous series published, our results show: the importance of the endoscopic suspicion of SMA syndrome, confirmed by CT scan; the preponderance of a longstading and chronic onset; a female preponderance; the importance of the nutritional counseling in the therapeutic approach; the absence of need for surgical intervention; the better diagnostic accuracy of the narrowing of the aorta-SMA distance, rather than the narrowing of the aortomesenteric angle. Further prospective studies, with a larger number of patients, are needed to clarify the best way to diagnose nd manage SMA syndrome.

Objective: Nowadays, an optional and effective medical surgery remains the gold standard for perianal fistulas. Hereby we reported preliminary rsults in favor of using Argentum-Quartz solution for both primary and recurrent perianal fisrtulas. Methods: Three patients with intersphimncter and extrasphinteric fistulas were enrolled. Argentum-Quartz solution was administrated twice a week for sa period of 4 weeks, followed by a pause of 8 days and then another 4 weeks of treatment, totally 16 administrations. After treatment, all patients were monitored for 4-months follow-up. Results: Complete closures of 2 extrasphinteric fistulas and a partial closure with absence of inflammation and superative phenomena in the intraspinteric fistula were both manifested. Conclusions: Selective treatment of perianal fistulas with argentum-quartz solution is safe and effective. and may represent a reliable alternative.

Inflammatory Bowel disease (IBD), such as Crohn's disease and ulcerative colitis, are pathologies characterized by a chronic inflammation of the gastrointestinal tract. Their etiopathogenesis is not yet fully understood. Immune system and heat shock proteins (HSPs) dysfunctions are considered to be among the most likely causes of these diseases. Butyrate is a short-chain fatty acid produced by intestinal microflora. It has a trophic, benefical and protective role in the colonic mucosa, and it also induces changes in Hsp levels and localization. It may therefore be a valuable complementary therapeutic agent when used alongside trraditional drugs (mesalazine and corticosteroids) to treat the production of butyrate in the endoluminal environment may promote clinical remission in IBD patients. Due to these characteristics, there has been keen interest in the use of butyrate as a novel therapeutic supplement in the recent years. The current findings need to be validated through further clinical trials to better define the bbiomolecular dynamics of butyrate in the colonocytes of IBD patients.

Patients with inflammatory bowel disease (IBD) have an increased risk of 10%-15% developing colorectal cancer (CRC) that is a common disease of high economic costs in developed countries. the CRC has been increasing in recent years and its mortality rates are very high. Multiple biological and biochemical factors are responsible for the onset nad progression of this pathology. moreover, it appears absolutely necessary to investigate the environmental factors favoring the onset of CRC and the production of colonic healt. the gut microflora, or microbiota, has an extensive diversity both quantitatively and qualitatively. in utero, the intestine of the mammalian fetus is sterile. Al birth, the intestinal microbiota in acquired by ingestion maternal anal or vaginal organisms, ultimately developing into a stable community, with marked variations in microbial composition between individuals. the development of IBD is often associated with qualitative and quantitative disorders of the intestinal microbial flora (dysbiosis). the healthy human gut arbours about 10 different bacterial species distributed in colony forming units which colonize the gastrointestinal tract. The intestinal microbiota plays a fundamental role in helath and the progeression of diseases such as IBD and CRC. in Healthy subjects, the main control of intestinal bacterial colonization occurs through gastric acidity but other factors such as endoluminal temperature, competition between different bacterial strains, peristalsis and drugs can influence the intestinal microenvironment. the microbiota exerts diverse physiological functions to include; growth inhibition of pathogenic microrganisms, synthesis of compounds useful for the trophysm of colonic mucosa, regulation of the intestinal lymphoid tissue and synthesis of amino acids. furthermopre, mucus seems to play an important role in protecting the intestinal mucosa and maintaining its integrity. changes in the microbiota composition are mainly influenced by diet and age, as well as genetic factors. Increasing evidence indicates that dysbiosis favors the production of genotoxins and metabolities associated with carcinogeneasis and induces dysregulation of the immune response wich promotes and sustains inflammation in IBD leading to carcinogenesis. a disequilibrium in gut microflora composition leads to the specific activation of gut associated lymphoid tissue. the associated chronic inflammatory process associated increases the risk of developing CRC. Ulcerative colitis and Crohn's diasease are the two major IBDs characterized by an early onset and extraintestinal manifestations, such as rheumatoid arthtritis. the pathogenesis of both diseases is complex and not yet fully known. however, it is widely accepted that an inappropriate immune response to microbial flora can play a pivotal role in IBD pathogenesis.

Inflammatory bowel disease (IBD) consists of two distinct clinical forms, ulcerative colitis (UC) and Crohn's disease (CD), with unknown aetiology, which nevertheless are considered to share almost identical pathophysiological backgrounds. Up to date, a full coherent mechanistic explanation for IBD is still lacking, but people start to realize that the pathogenesis of IBD involves four fundamental components: the environment, gut microbiota, the immune system and the genome. As a consequence, IBD development might be due to an altered immune response and a disrupted mechanism of host tolerance to the non-pathogenic resident microbiota, leading to an elevated inflammatory response. Considering the available data arising from the scientific literature, here reviewed, in CD, a benefit of probiotics remains unproven; in UC, a benefit of probiotics remains unproven, even if E. coli Nissle 1917 seems promising in maintaining remission and it could be considered an alternative in patients intolerant or resistant to 5-ASA preparations; in pouchitis, small controlled trials suggest a benefit from VSL no. 3 in the primary and secondary prevention of pouchitis; in IBD-associated conditions, a benefit of probiotics remains unproven. However, well-designed randomized control clinical trials are necessary to understand the undoubted role of these agents in the management of gut physiology in health and disease.

Pro-inflammatory cytokine, i.e., IL-1 mediate the inflammatory response and are genetically regulated in periodontal diseases. Strong association was found between the composite genotype allele 2 of IL-1β+3954 and IL-1α-889 and severe chronic periodontitis. The aim of this study is to determine the prevalence of IL-1β+3954 and IL-1α-889 polymorphism in a group of Lebanese individuals of homogeneous ethnicity and the possible association between genotype positive individuals and the severity of periodontal disease. One hundred and fifty-seven patients aged 53.29±13.13 years participated in the study. Subjects were classified as follows: 1) healthy subjects with no attachment loss >1mm and no clinical signs of gingival or periodontal inflammation; 2) diseased subjects with mild periodontitis (less than 15% of global periodontal bone loss); 3) subjects with moderate periodontitis (less than 4 interproximal sites with bone loss = or >50% and mean bone loss between 15 and 30%); 4) subjects with severe periodontitis (more than 7 interproximal sites with >50% bone loss and mean bone loss >35%). Blood samples were taken and analyzed for polymorphism in the IL-1α gene at position +4845 and in the IL-1β gene at position +3953. Statistical analysis was performed using chi-square test, Fisher Exact test, and ANOVA followed by Bonferroni multiple comparisons. The prevalence of genotype-positive subjects was 52.3% in the healthy control group and 42 % in the diseased group. Positive genotype heterozygous of allele 1 and 2 for IL-1β+3954 and IL-1α-889 did not represent in this study a major risk for chronic periodontitis (p=0.590). Only subjects homozygous for allele2 of the IL-1β+3954 and IL-1a-889 were significantly more at risk for severe periodontitis with OR of 51.42.

Objective. To evaluate the hypothesis of human dental pulp cell death during Orthodontic Treatement (O.T.) and the degree of apoptosis through the expression level of the proteins Caspase-3,-9, TUNEL and HSP60. Materials and methods. Human dental Pulp were coming from both male and female patients (N=20; age 10-14years). The technique used was the Straight Wire, which involves Nickel-Titanium or Steel archwires. The increase of pressure applied on teeth was gradual. Some patients were subjected to a premolar extraction after 3 months treatment, and others after 6 months. Samples were Bouin-fixed, paraffin-embedded and afterwards processed for immunohistochemistry using anti-caspase-3,-9 antibody, anti-HSP60 and TUNEL. Results. Increasing of Caspase-3,-9 expression occurred in 3 and 6 months O.T. samples, while in control pulps positivity was detected mainly at odontoblasts level. HSP60 was not expressed in control samples and very weak in 3 months O.T. samples, it was expressed instead in 6 months O.T. samples, the expression of TUNEL is evident in all samples but increased at 3 and 6 months specimen. Conclusion. Our hypothesis is supported by the increasing expression of Caspase-3,-9, HSP60 and TUNEL after 3 and 6 months of orthodontic traction revealing a time-dependent relationship., Italian Journal of Anatomy and Embryology, Vol 116, No 1 (Supplement) 2011

Objective. This study seeks to clarify the histological origin of apical lesions, through the expression of certain cytokeratins.Study design. In 3 years 30 patients were selected. After clinical and radiological exams were chosen patients who had severe apical lesions and tooth decay with exposure of the pulp chamber left untreated for very long periods (more the 12 months). Serial slides were prepared both for immunohistochemistry and Hematoxylin- Eosin. Material and methods. Twenty specimens coming from the 30 patients were used for our purpose. All periapical lesions were surgically extracted and fixed in Bouin mixture, and embedded in paraffin. Samples were processed immunohistochemically employing the instructions of the Envision Dako cytomation kit. Monoclonal antibobies against Cytokeratins (CKs) 1, 5 , 8, 10 and 14 were used. Slides were observed with Leica Laborlux-S microscope and the image were acquired with NIKON DSL2 System. Each sample has been analyzed with a “double-blind” system by two different operators. Moreover, the digital images acquired have been compared to an image analysis tools by Adobe photoshop CS5 Extended. Results. CKs 1, 5 and 8 are expressed in all samples at external epithelial layer with no statistically significant differences. CK 10 is weakly expressed in some epithelial cells lining the periapical lesion. CK 14 was negative in most samples, and little positive in some specimens. Conclusion. Our results suggest that most of the apical lesions we studied have an epithelial origin. The absence of CK14 positivity may be explained by the fact that during the extirpation of the lesion the basal epithelium remained attached to the surrounding bone., Italian Journal of Anatomy and Embryology, Vol 116, No 1 (Supplement) 2011

The endocannabinoid system plays a key role in energy homeostasis, with agonists and antagonists of CB1 receptors acting centrally to stimulate and inhibit food intake, respectively. The currently available literature, about islets cannabinoid receptors expression and function, is confusing and often contradictory. Aim of our study is compare the expression of CB1 receptors in normal and obese Zucker (ZDF) rats.12 Male ZDF (6 lean and 6 fa/fa) aged 8 weeks were obtained from Harlan Italy S.r.l. Each rat was fed with standard diet and unlimited water. Specimens were taken at the age of 8-12-16 weeks after birth. Pancreas samples were fixed in formaline and embedded in paraffin. Section were processed immunohistochemically using DakoCytomation EnVision kit for anti CB1antibody (Biosource Europe S.A.). Leica microscope, with a DSL2 Nikon was used to observe in double blind. Images were submitted at the image analysis tools of the Photoshop CS5Ex. At the same time pancreas specimens were frozen in liquid nitrogen and stored at -80°C until use. A mRNA was extracted for all samples and a RT PCR was performed. The pancreatic islets cells in fa/fa show deep apoptotic alterations. Our observations show a CB1 expression extended to most of the cell population (eighth week), up to a structural disorganization in the sixteenth week; the expression of CB1 receptor is upregulated in fa/fa compared to lean. These results according to the involvement of endocannabinoid system in the disregulation of the food intake mechanism and a prevalence of this system in the obesity., Italian Journal of Anatomy and Embryology, Vol 116, No 1 (Supplement) 2011

Recent studies document that CB1 cannabinoid receptors, considered since its first identification as “brain specific”, could be expressed by peripheral tissues targets (adipose organs, enteric nervous system, striated muscle, epatocytes). This receptors were found in the GI tract of different species, including mice, rats, guinea pigs, pigs and humans. Endocannabinoids play a role in the pathophysiology of the gastrointestinal tract. They play a role in emesis, acid-related disorders, motility-related disorders, irritable bowel syndrome and diarrhea, and in inflammatory bowel disease. Endocannabinoid system might be involved in cancer differentiation, growth and cell migration. Distribution of receptors in different colonic segment is not known. We studied CB1 receptors distribution in 10 patients colonic segments; the present report shows preliminary results. Fragments of sigma, transverse and ascending human colon were obtained during endoscopic screening procedure. Materials and Methods The specimens, for immunohistochemistry (IHC), were fixed in buffered formalin and embedded in paraffin; obtained sections were processed with anti CB1 (Biosource Europe S.A.) by EnVision+System HRP (AEC) and have been studied with photomicroscope Leica DMLB. The specimens for the Reverse Transcription Polymerase Chain Reaction (RT-PCR) were frozen in liquid nitrogen and stored at -80° until use. Total RNA extraction was performed using the “illustra RNA spin Mini Kit”. RT reaction was performed using the “Enhanced avian HS RT PCR kit” The PCR was performed using the “PCR enzyme Selection Kit-High specificity”. Results and Discussion Following the endoscopic procedure was performed anatomopathological examination of specimens. The results have revealed that four of the 10 patients had a polyp the others were not suffering from any disease of the colon. Our immunohistochemical evaluation has revealed the presence of CB1 receptors expressed by regional differences in patients who had a polyp. This reactivity appeared to be lower than that shown in non-pathological patients. The PCR results instead of doubtful interpretation. In fact, despite being detected in some cases also marked a positive control, in two cases, the PCR is a totally negative compared with a positive IHC. Since the number of cases studied is not statistically significant, it is our intention to continue to evaluate additional patients both normal and suffering from polyposis in order to clarify the difference beetween immunohistochemical and molecular biology results.

The full-term human umbilical cord is made of three blood vessels (two arteries and a vein) surrounded by the Wharton’s jelly, a soft connective tissue made of few mesenchymal stromal cells and an abundant extracellular matrix. Both endothelial and Wharton’s jelly cells are versatile in their differentiation potential; they have shown to be able to differentiate into several cell lineages. Since the differentiation potential of these cells is very wide, we thought it could be interesting to investigate the expression of several cell differentiation markers in the different regions of human umbilical cord. Immunohistochemistry showed the expression of E-cadherin and cytokeratins in the amniotic epithelium, cytokeratins were also expressed in the cells of Wharton’s jelly. Actin and Desmin immunoreactivity localizes in vessel musculature and in Wharton’s jelly. CD31 was expressed only in vessels endothelium, while CD68 by many cells scattered in the Wharton’s jelly and in the vascular compartment.

Introduction: Msx1and Pax9, are genes expressed in mesenchymal cells during the odontogenesis that are required for tooth formation. Our investigation aimed to study the expression of these genes in two sources of dental mesenchymal cells. Stem Cells from Human Exfoliated Deciduous teeth (SHED) and Human Embryonic Dental Mesenchymal Cells (HTM) were used. Regulation of gene expression in these cells by FGF, Wnt, BMP4 and Shh signalling pathways together with the effects of tooth matrix proteins (EMD) was investigated. Materials and Methods: Cells were grown in 6 well plates in 3 ml MSCGM medium (Lonza) containing Glutamax, 10% FBS and gentamicin Sulfate. Cells were grown to confluence and when 80% confluent, they were treated for 24 hours with either 20 ng per ml BIO (Gsk3 inhibitor), 1.5µl per ml of porcine dental matrix proteins (EMD), 0.4µl per ml of Fgf8 and 4µl per ml of DMSO (control). RNA was extracted and purified according the RNeasy-kit-protocol from Qiagen. RNA quantitation was done using a Bio Photometer (Eppendorf) in 2:100 dilutions of the samples with nuclease-free water. Quantitative analysis was performed using Rotor Gene Q-serier softhware. 10µl of mixture was made with 5µl of Sensimix- syber green from Quantace, 0.2µl F- primer , 0.2µl R-primer and 4.6µl of cDNA. Results: Complex patterns of changes in the levels of gene expression were observed that were both cell and treatment specific. In particular BMP4 treatment resulted in large upregulation of Msx1 and Pax9 gene expression in both cell types. Differences in gene expression observed between HTM and SHED cells identify possible reasons why SHED cells respond differently to HTM in tissue recombinations directed towards producing biological replacement teeth.

The full-term human umbilical cord is made of three blood vessels ( two arteries and a vein) surrounded by the Wharthon's jelly, a soft cennective tissue made of new mesenchymal stromal cells and an abundant extracellular matrix. Both endothelial and Wharton's jelly are versdatile in their differenciation potential;tewhy have shown to be able to differentiate into sevaral cell lineages. Since the differentiation potential of these cells is very wide, we thought it could be interesting to investigate the expression of several cell differentiation markers in the different regions of human umbilical cord. Immunohistochemistry showed the expression of E- Cadherin and cytokeratyns in the amniotic epithelium, cytokeratins were also expressed in the cells of Wharthon's jelly. Actin and Desmin immnuoreactivity localizes in vessels musculature and in Wharton's jelly. CD31 was expressed only in vessels endothelium, while CD68 by many cells scattered in teh Wharton's jelly and in the vascular compartment.

Objective: To evaluate the hypothesis of human dental pulp cell death during orthodontic treatement (O.T) and the degree of apoptosis through the expression level of the proteins Caspase-3,-9, TUNEL and HSP60. Materials and methods: Human dental Pulp were coming from both male and female patients (N=20; age 10-14years). The technique used was the Straight Wire, which involves Nickel-Titanium or Steel archwires. The increase of pressure applied on teeth was gradual. Some patients were subjected to a premolar extraction after 3 months treatment, and others after 6 months. Samples were Bouin-fixed, paraffin-embedded and afterwards processed for immunohistochemistry using anti-caspase-3,-9 antibody, anti-HSP60 and TUNEL. Results: Increasing of caspase-3,-9 expression occurred in 3 and 6 months O.T. samples, while in control pulps positivity was detected mainly at odontoblasts level. HSP60 was not expressed in control samples and very weak in 3 months O.T. samples, it was expressed instead in 6 month O.T. samples, the expression of Tunel is evident in all samples but increased at 3 and 6 months specimens . Conclusion: Our hypothesis is supported by the increasing expression of Caspase-3,-9 , HSP60 and Tunel after 3 and 6 months of orthodontic traction revealing a time-dependent relationship.

OBJECTIVE: To study the cytology profile of cervical smears and the respective prevalence and incidence of certain cervico-vaginal infections detectable by routine Pap smear cytology in Lebanese women from 2002 to 2006. METHODS: Pap smear cytology results were compiled from the archives of the “Institut National de Pathologie” for the period extending from 2002 until 2006. This study covered 118,230 cervical specimens obtained from Lebanese women attending clinics and hospitals in all the five districts of Lebanon; prevalence and incidence rates for infections detectable by routine Pap smear examination were determined. RESULTS: A rise in prevalence of these infections by 2.1% (2,555) from 2002 to 2006 was revealed. A doubling of Pap smears showing “HPV-associated changes” was detected (1.4% in in 2002 to 2.9% in 2006) and a simultaneous almost 7-fold increase of Atypical Squamous Cells of Undetermined Significance (ASCUS) cytology was detected during this period; the rise in ASCUS cytology was age-dependent. Moreover, a 60% increase in prevalence of bacterial vaginosis (2.3% in 2002 to 3.7% in 2006) and a more than 3-fold decline in Trichomonas vaginalis infection (1% in 2002 to 0.3% in 2006) were also noted in this population during this period. CONCLUSION: An increase in the prevalence and incidence of cervico-vaginal infections detectable by Pap smear cytology in Lebanese women was revealed from 2002 to 2006. Such changes could point to recent modifications of sexual and health behaviors in the Lebanese community.

Italian Journal of Anatomy and Embryology, Vol 115, No 1/2 (Supplement) 2010

Italian Journal of Anatomy and Embryology, Vol 115, No 1/2 (Supplement) 2010

Introduction. Cytokeratins (Cks) are the proteins that constitute intermediate filaments. The pattern of expression of cytokeratins is frequently organ or tissue specific and depends mainly on the type of epithelium, the level of differentiation and the stage of development. With this study we tried to make light on the pattern of expression of a wide range of CKs in human umbilical cord at term. Materials and methods. We investigated the expression of CKs through immunohistochemistry and RT-PCR assay. Results. AE1/AE3 antibody reacts with the basic CKs 1, 2, 3, 4, 5, 6, 7 and 8, and with the acidic CKs 10, 13, 14, 15, 16 and 19. The reactivity for this antibody is localized in the amniotic epithelium. Fibroblasts of the Wharton’s jelly did not react with this antibody. Endothelial cells and some cells of the vessel wall seem to express CKs at low levels. Reactivity for 34βE12 antibody (that recognizes CKs 1, 5, 10 and 14) is localized in the cells of the umbilical epithelium, while all the other regions of the umbilical cord did not react with the antibody. The immunoreactivity for MNF116 antibody (that recognizes CKs 5, 6, 8, 17 and 19) is restricted to the cells of the umbilical epithelium while all the other cells of the umbilical cord seems not to express these types of Cks. RT-PCR analysis revealed gene expression for CKs 5, 6, 8, 10, 14 and at a lower level also cytokeratins 1 and 17. Conclusions. We identified the expression of several types of CKs in human umbilical cord at term both at proteic and RNA level. References. 1) Bea F, Bär H, Watson L, Blessing E, Kübler W, Kreuzer J, Jahn L.Cardiac alpha-actin in smooth muscle cells: detection in umbilical cord vessels and in atherosclerotic lesions.Basic Res Cardiol. 2000 Apr;95(2):106-13. 2) Livasy CA, Karaca G, Nanda R, Tretiakova MS, Olopade OI, Moore DT, Perou CM.P henotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol. 2006 Feb;19(2):264-71.

The oral cavity is exposed to chronic or recurrent, physical and chemical trauma that could lead to mucosal reactions (e.g. hyperplasia, dysplasia and tumors). The objective of this study is to investigate the expression and the possible changes of the two matrix metalloproteinases MMP-2 and MMP-9 in normal and pathological human oral mucosa samples. Normal oral mucosa samples and three different types of pathological conditions (hyperplasia, dysplasia and carcinoma) were used for this study. Immunohistochemical analysis was used to evaluate protein expression for the two enzymes, while Reverse Transcription ? Polymerase Chain Reaction (RT-PCR) was used to investigate gene expression. Image analysis was used to give a quantitative evaluation of the immunohistochemical data. In control samples we identified a weak expression of both MMP-2 and MMP-9 in the epithelial layers. In hyperplasia samples MMPs expression is limited to epithelial layers but the immunoreactivity is more intense than in the control. In dysplasia and carcinoma samples the two matrix metalloproteases are expressed not only in epithelium but also in some cells of the connective tissue and in the vessel walls. Qualitative RT-PCR and image analysis confirmed the immunohistochemical data. The results obtained in this study suggest the existence of a possible relationship between the entity of morphological disorganization of the oral mucosa in different pathologies and the increase of MMP-2 and MMP-9 expression

Ventricular peritoneal derivations may determinate conditions in the tissues, which may then create fibrous tissues around them. They include cases with catheters of the SEM and they show that when the fibrous tissues are formed, the outer surface is irregular. However, they are not determined through phystolosis or irregular inside the surface

This study was aimed to explain the functional role of mediation in the organs of the male reproductive system (prostate and seminal vesicles of rat and hamster), representing throught the visualization of adrenergic fibres (Falck Method), cholinergic fobres (Martinez-Rodriguez method) and by immunohistochemical methods to detect the P substance and the CGRP (PAP) in glandular structures. The adrenocholinergic and peptidergic mediators have a growing interest for their synergic action in the control of contractility, vasodilatation and most likely, of the secretory activity of the epithelium, probably expressed by andocrine-paracrine mechanisms.

Introduction. For several years, our histology laboratory has worked in co-operation with the Winchmore Hill Dental Practice studying the activity of Acetylcholinesterase and some neuropeptides (CGRP, Sub. P, Enkephalins, Endorphins)(1) in orthodontic treated human dental pulp to clarify force's action. It seems that recent data do not yet, fully elucidate the exact effects of the force applied on teeth. For this reason we are investigating whether the traction is involved in some cases of pulpal death. In this study we focused on the expression of Caspase-9 and β-Endorphine. Materials and Methods. The expression of the 2 peptides has been identified through immunohistochemistry assay: not treated dental pulp and treated dental pulp (six months orthodontic traction, the force was applied using 0.12, 0,14, 0.16 NiTi archwire). Results. Control pulp: weak positivity to β-Endorphine of intraparechymal and vascular nervous fibres. Treated pulp: the pulpal morphology is altered with oedema, inflammatory infiltrate and disorganized odontoblastic epithelium. Intense β-Endorphine reactivity of intraparechymal and perivascular nervous fibres; strong positivity of odontoblasts. Control pulp: Caspase-9 positivity in some odontoblasts and pulpal parenchymal cells. Treated pulp: We identified a strong nuclear Caspase-9 staining in many odontoblasts and some parenchymal cells. Vessels endothelium appears to be positive too. Conclusions. We observed weak changes in the expression of both β-Endorfin and Caspase-9 in orthodontically treated pulps compared to control pulps. The present result confirm our purpose to continue study the action of orthodontic traction for longer time to understand better the role of those proteins. References. 1) Angelo Leone, Roselyn A. Jurjus, Aldo Gerbino, Luana Lipari, Annamaria Mauro and Maria Buscemi. Twenty years' history of immunohistochemical mammals dental pulp studies. Experimental Medicine Revews (2007); 223-232.