Cushing's syndrome (CS) secondary to adrenocorticotropic hormone (ACTH) producing tumours is a severe condition with a challenging diagnosis. Ectopic ACTH-secretion often involves neuroendocrine ...tumours (NET) in the respiratory tract. ACTH-secreting small intestine neuro-endocrine tumours (siNET) are extremely rare entities barely reported in literature. This review is illustrated by the case of a 75-year old woman with fulminant ectopic CS caused by a ACTH-secreting metastatic siNET. Severe hypokalemia, fluid retention and refractory hypertension were the presenting symptoms. Basal and dynamic laboratory studies were diagnostic for ACTH-dependent CS. Extensive imaging studies of the pituitary and thorax-abdomen areas were normal, while 68GaGa-DOTATATE PET-CT revealed increased small intestine uptake in the left iliac fossa. The hypercortisolism was well controlled with somatostatin analogues, after which a debulking resection of the tumour was performed. Pathological investigation confirmed a well-differentiated NET with sporadic ACTH immunostaining and post-operative treatment with somatostatin analogues was continued with favourable disease control.
Background
Lactobacillus species might positively affect gastrointestinal motility. These Gram‐positive bacteria bind Toll‐like receptor 2 (TLR2) that elicits anti‐inflammatory activity and exerts ...protective effects on damage induced by lipopolysaccharide (LPS). Whether such effect occurs in gastrointestinal smooth muscle has not been established yet. Aim of this study was to characterize the effects of Lactobacillus rhamnosus GG (LGG) and of supernatants harvested from LGG cultures on human colonic smooth muscle and to explore their protective activity against LPS‐induced myogenic morpho‐functional alterations.
Methods
The effects of LGG (ATCC 53103 strain) and of supernatants have been tested on both human colonic smooth muscle strips and isolated cells in the absence or presence of LPS obtained from a pathogenic strain of Escherichia coli. Their effects on myogenic morpho‐functional properties, on LPS‐induced NFκB activation, and on cytokine production have been evaluated. Toll‐like receptor 2 expression has been analyzed by qPCR and flow cytometry.
Key Results
Lactobacillus rhamnosus GG exerted negligible transient effects per se whereas it was capable of activating an intrinsic myogenic response counteracting LPS‐induced alterations. In particular, both LGG and supernatants significantly reduced the LPS‐induced morpho‐functional alterations of muscle cells, i.e. cell shortening and inhibition of contractile response. They also hindered LPS‐induced pro‐inflammatory effects by decreasing pro‐inflammatory transcription factor NFκB activation and pro‐inflammatory cytokine IL‐6 secretion, and restored the secretion levels of anti‐inflammatory cytokine IL10.
Conclusions & Inferences
Taken together these data demonstrate that LGG protects human colonic smooth muscle from LPS‐induced myogenic damage and might be beneficial on intestinal motor disorders due to bacterial infection.
This study provides conclusive proof of protective effect of Lactobacillus rhamnosus GG (LGG) and derived factors against LPS‐induced human colonic smooth muscle alterations. In fact, this study supports the evidence that LGG interferes with the muscular inflammatory reaction triggered by infection and might reduce the risk of progression toward a postinfective disorder. Furthermore, these experimental data, obtained either on human isolated cell or muscle strips, provide a rationale to design clinical studies where the efficacy of probiotics in bacterial‐related gut motor disorders would ultimately be defined.
A prospective registration of patients with colorectal cancer and a colonoscopy within the last 10 years. We tried to classify these post-colonoscopy colorectal cancers (PCCRCs) by most reasonable ...explanation and into subcategories suggested by the World Endoscopy Organization (WEO) and calculated the unadjusted PCCRC rate.
47 PCCRCs were identified. The average age at diagnosis of PCCRC was 73 years. PCCRCs were more located in the right colon with a higher percentage of MSI-positive and B-RAF mutated tumours. The average period between index colonoscopy and diagnosis of PCCRC was 4.2 years. Sixty-eight % of all PCCRCs could be explained by procedural factors. The mean PCCRC-3y of our department was 2.46%.
The data of our centre are in line with the data of the literature from which can be concluded that most postcolonoscopy colorectal cancers are preventable. The PCCRC-3y is an important quality measure for screening colonoscopy. Ideally all centres involved in the population screening should measure the PCCRC-3 y annually, with cooperation of the cancer registry and reimbursement data provided by the Intermutualistic Agency (IMA).
Mesenchymal cells transdifferentiation and extracellular matrix deposition are involved in the fibrotic process of Crohn's disease (CD). Mesenchymal smooth muscle cells (SMCs) de-differentiation, ...driven by Platelet-derived growth factor (PDGF) that counteracts Transforming growth factor (TGF-β) has been studied in vascular muscle. The role of SMCs in intestinal fibrogenesis is still not clearly elucidated. Aim of the study was to evaluate the possible myogenic contribution to CD fibrotic process through the comparative analysis of histological, morphometric and molecular alterations occurring in human smooth muscle. Full thickness specimens were obtained from CD (non-involved and stenotic tracts) and healthy (control) ileum. Tissues were processed for histological and immunohistochemical (IHC) analyses and SMCs were isolated from the muscularis propria for morphofunctional and molecular (qPCR) analyses. CD stenotic ileum showed a significant increased thickness of all layers compared to CD non-involved and control ileum. IHC revealed an overexpression of α-smooth muscle actin and collagens I-III throughout all intestinal layers only in stenotic tracts. The two growth factors, PDGF and TGF-β, showed a progressive increase in expression in the muscle layer from CD non-involved to stenotic tracts. Freshly isolated SMCs presented alterations in CD non-involved tracts that progressively increased in the stenotic tracts consisting in a statistical increase in mRNA encoding for PDGF-β and collagen III, paralleled to a decrease in TGF-β and Tribbles-like protein-3 mRNA, and altered morphofunctional parameters consisting in progressive decreases in cell length and contraction to acetylcholine. These findings indicate that intrinsic myogenic alterations occur in CD ileum, that they likely precede stricture formation, and might represent suitable new targets for anti-fibrotic interventions.
Background
Changes in intestinal motility are likely to contribute to irritable bowel syndrome (IBS) pathophysiology. The aim of the study was to investigate the effects of IBS mucosal supernatants ...on human colonic muscle contractility.
Methods
Supernatants were obtained from biopsies of 18 IBS patients—nine with constipation (IBS‐C) and nine with diarrhea‐predominant IBS (IBS‐D)—and nine asymptomatic subjects, used as controls. Colonic circular smooth muscle strips or isolated cells (SMC) were exposed to control or IBS supernatants. Spontaneous phasic contractions on strips and morphofunctional parameters on cells were evaluated in basal conditions and in response to acetylcholine (Ach). Incubation with IBS supernatants was also conducted in the presence of antagonists and inhibitors (namely histamine, protease and prostaglandin antagonists, nuclear factor‐kappa B inhibitor, catalase, NADPH oxidase inhibitor, and the cAMP‐ and/or cGMP‐cyclase inhibitors).
Key Results
Exposure to IBS‐C and IBS‐D supernatants induced a significant reduction in basal tone and Ach‐elicited contraction of muscle strips and a significant shortening and impairment of Ach contraction of SMCs. The NADPH oxidase inhibitor prevented the effect of supernatants, while the protease antagonist only IBS‐C effect. No effect was observed with the other antagonists and inhibitors. Dilution of IBS‐D supernatants partially restored the effects only on SMCs, whereas dilution of IBS‐C supernatants significantly reverted the effects on muscle strips and Ach‐elicited response on SMC.
Conclusions & Inferences
Supernatants from mucosal biopsies of IBS patients reduce colonic contractility. The observed impairment was concentration dependent, likely occurring through intracellular oxidative stress damage, involving different neuromotor mechanisms depending on the IBS subtype.
The aim of the study was to investigate the effects of IBS mucosal supernatants on human colonic muscle contractility. Supernatants were obtained from biopsies of IBS patients and asymptomatic subjects. IBS supernatants reduced colonic contractility mucosal likely through muscular intracellular oxidative stress damage. Depending on the IBS subtype, further different neuromotor mechanisms are involved.
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► Administration of Brazilian green propolis induced alterations in the morphophysiology of reproductive organs. ► Brazilian green propolis induced higher sperm production. ► Propolis increased ...epithelium height of epididymis initial segment epididymis. ► Propolis did not induce increase on epididymis oxidative stress level.
Basal generation of reactive oxygen species (ROS) is essential for male reproductive function, whereas high ROS levels may be linked to low quality of sperm and male infertility. The number of antioxidants known to inflict damage is growing, and it will be of interest to study natural products, which may have this activity. Since the epididymis is known to play an important role in providing the microenvironment for sperm maturation and storage of sperm, this study was undertaken to evaluate the morphometric-stereological and functional alterations in the epididymis after chronic treatment with low doses of Brazilian green propolis, which is known for its antioxidant properties. For this purpose, forty-eight adult male Wistar rats were treated with 3, 6 and 10mg/kg/day of aqueous extract of Brazilian green propolis during 56days and morphological parameters, sperm production and number of sperm in rat epididymis and oxidative stress levels were analyzed. The results showed higher sperm production and greater epithelium height of the epididymis initial segment and no induction of oxidative stress in treated animals. Further studies are needed to fully understand the effects of propolis on the reproductive system but our results showed that it could alter male reproductive function.
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