Spasmolytic Effects of Aphanizomenon Flos Aquae (AFA) Extract on the Human Colon Contractility.

The blue-green algae Aphanizomenon flos aquae (AFA), rich in beneficial nutrients, exerts various beneficial effects, acting in different organs including the gut. Klamin® is an AFA extract particularly rich in -PEA, a trace-amine considered a neuromodulator in the central nervous system. To date, it is not clear if -PEA exerts a role in the enteric nervous system. The aims of the present study were to investigate the effects induced by Klamin® on the human distal colon mechanical activity, to analyze the mechanism of action, and to verify a -PEA involvement. The organ bath technique, RT-PCR, and immunohistochemistry (IHC) were used. Klamin® reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions. EPPTB, a traceamine receptor (TAAR1) antagonist, significantly antagonized the inhibitory effects of both Klamin® and exogenous -PEA, suggesting a trace-amine involvement in the Klamin® effects. Accordingly, AphaMax®, an AFA extract containing lesser amount of -PEA, failed to modify colon contractility. Moreover, the Klamin® effects were abolished by tetrodotoxin, a neural blocker, but not by L-NAME, a nitric oxide-synthase inhibitor. On the contrary methysergide, a serotonin receptor antagonist, significantly antagonized the Klamin® effects, as well as the contractility reduction induced by 5-HT. The RT-PCR analysis revealed TAAR1 gene expression in the colon and the IHC experiments showed that 5-HT-positive neurons are co-expressed with TAAR1 positive neurons. In conclusion, the results of this study suggest that Klamin® exerts spasmolytic effects in human colon contractility through -PEA, that, by activating neural TAAR1, induce serotonin release from serotoninergic neurons of the myenteric plexus

Tas-102 in metastatic colorectal cancer (MCRC): Efficacy, tolerability, and quality of life in heavily pretreated elderly patients: A real-life study

Background: TAS-102 is an oral monotherapy, combining trifluridine and tipiracil hydrochloride, indicated for the treatment of pretreated metastatic colorectal cancer (mCRC). The aim of this real-life study is to evaluate the efficacy and safety of TAS-102 in heavily pretreated elderly patients with mCRC whose disease has progressed with standard therapies. Methods: In this retrospective observational study, we enrolled 50 elderly patients >70 years of age (median age 78 years) with a diagnosis of mCRC who were previously treated or were not considered candidates for treatment with other available therapies. Patients aged >70 years with advanced colorectal cancer and with an ECOG performance status of grade 0 (n=18) or grade 1 (n=32) were included. Overall survival and progression-free survival were the primary endpoints, whereas objective response rate, tolerability, and quality of life were the secondary endpoints. Results: Treatment with TAS-102 appeared to be well tolerated and side effects were generally mild, achieving disease control and a benefit on quality of life. The median overall survival was 6.7 (95% CI 5.7-11.3) and the median progression-free survival was 2.1 months (95% CI 1.2-3.2), estimated using the Kaplan-Meier method. Conclusion: TAS-102 represents a manageable and effective therapeutic opportunity and appeared to be well tolerated with generally mild side effects in elderly patients with mCRC who were heavily pretreated with standard therapies

POUCHITIS: A TRIDIMENSIONAL VIEW

The preferred surgical treatment of ulcerative colitis (UC) and familial adenomatous polyposis (FAP) is represented by proctocolectomy with ileal pouch-anal anastomosis (IPAA). However, patients with UYC who have undergone IPAA are prone to develop several complications, which include surgery related/mecchanical complications; inflammatory or infectious disoreders; dysplasia or neoplasia; and systemic or metabolic disorders. Pouchitis, which is defined as the acute and/or chronic inflammation of the ileal reservoir, represent the most common long-term adverese sequela after IPAA. Gut microbiota play a pivotal role in the initiation and disease progression of pouchitis. Pouchitis can be classified according to the activity of the disease, the duration of the symptoms, the pattern of the disease or response to antibiotic therapy. Patients with IPAA for UC tend to experience a variety of symptoms that may eventually lead to pouch excision thereby necessitating the construction of a permanent ileostomy. To date, the ethiology, the diagnosis and the medical management of pouchitis represent a clinical challenge. In fact pouchitis range from a disease with an acute antibiotic-responsive presentation to a chronic antibiotic-refractory form, with subsequent different disease mechanism and clinical course. A tridimensional and multidisciplinar approach, including endoscopy, histology, and laboratory testing is widely helpful to identify the diferent phenotypes of the disease and to manage correctly its treatment

miRNeye: a microRNA expression atlas of the mouse eye

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are key regulators of biological processes. To define miRNA function in the eye, it is essential to determine a high-resolution profile of their spatial and temporal distribution.</p> <p>Results</p> <p>In this report, we present the first comprehensive survey of miRNA expression in ocular tissues, using both microarray and RNA <it>in situ </it>hybridization (ISH) procedures. We initially determined the expression profiles of miRNAs in the retina, lens, cornea and retinal pigment epithelium of the adult mouse eye by microarray. Each tissue exhibited notably distinct miRNA enrichment patterns and cluster analysis identified groups of miRNAs that showed predominant expression in specific ocular tissues or combinations of them. Next, we performed RNA ISH for over 220 miRNAs, including those showing the highest expression levels by microarray, and generated a high-resolution expression atlas of miRNAs in the developing and adult wild-type mouse eye, which is accessible in the form of a publicly available web database. We found that 122 miRNAs displayed restricted expression domains in the eye at different developmental stages, with the majority of them expressed in one or more cell layers of the neural retina.</p> <p>Conclusions</p> <p>This analysis revealed miRNAs with differential expression in ocular tissues and provided a detailed atlas of their tissue-specific distribution during development of the murine eye. The combination of the two approaches offers a valuable resource to decipher the contributions of specific miRNAs and miRNA clusters to the development of distinct ocular structures.</p

Extra-Intestinal Manifestations of Familial Adenomatous Polyposis

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder, which results from a germ line mutation in the APC (adenomatous polyposis coli) gene. FAP is characterized by the formation of hundreds to thousands of colorectal adenomatous polyps. Although the development of colorectal cancer stands out as the most prevalent complication, FAP is a multisystem disorder of growth. This means, it is comparable to other diseases such as the MEN syndromes, Von Hippel-Lindau disease and neurofibromatosis. However, the incidence of many of its clinical features is much lower. Therefore, a specialized multidisciplinary approach to optimize health care—common for other disorders—is not usually taken for FAP patients. Thus, clinicians that care for and counsel members of high-risk families should have familiarity with all the extra-intestinal manifestations of this syndrome. FAP-related complications, for which medical attention is essential, are not rare and their estimated lifetime risk presumably exceeds 30%. Affected individuals can develop thyroid and pancreatic cancer, hepatoblastomas, CNS tumors (especially medulloblastomas), and various benign tumors such as adrenal adenomas, osteomas, desmoid tumors and dental abnormalities. Due to improved longevity, as a result of better prevention of colorectal cancer, the risk of these clinical problems will further increase