Andrea Porzionato

Toll-Like Receptor 2 Regulates Intestinal Inflammation by Controlling Integrity of the Enteric Nervous System

BACKGROUND & AIMSnIn the intestines, Toll-like receptor 2 (TLR2) mediates immune responses to pathogens and regulates epithelial barrier function; polymorphisms in TLR2 have been associated with inflammatory bowel disease phenotype. We assessed the effects of TLR2 signaling on the enteric nervous system (ENS) in mice.nnnMETHODSnTLR2 distribution and function in the ileal neuromuscular layer of mice were determined by immunofluorescence, cytofluorimetric analysis, immunoprecipitation, and immunoblot analyses. We assessed morphology and function of the ENS in Tlr2(-/-) mice and in mice with wild-type Tlr2 (wild-type mice) depleted of intestinal microbiota, using immunofluorescence, immunoblot, and gastrointestinal motility assays. Levels and signaling of glial cell line-derived neurotrophic factor (GDNF) were determined using quantitative reverse transcriptase polymerase chain reaction, immunohistochemistry, and immunoprecipitation analyses. Colitis was induced by administration of dextran sulfate sodium or 2,4 dinitrobenzensulfonic acid to Tlr2(-/-) mice after termination of GDNF administration.nnnRESULTSnTLR2 was expressed in enteric neurons, glia, and smooth muscle cells of the intestinal wall. Tlr2(-/-) mice had alterations in ENS architecture and neurochemical profile, intestinal dysmotility, abnormal mucosal secretion, reduced levels of GDNF in smooth muscle cells, and impaired signaling via Ret-GFRα1. ENS structural and functional anomalies were completely corrected by administration of GDNF to Tlr2(-/-) mice. Wild-type mice depleted of intestinal microbiota had ENS defects and GDNF deficiency, similar to Tlr2(-/-) mice; these defects were partially restored by administration of a TLR2 agonist. Tlr2(-/-) mice developed more severe colitis than wild-type mice after administration of dextran sulfate sodium or 2,4 dinitrobenzensulfonic acid; colitis was not more severe if Tlr2(-/-) mice were given GDNF before dextran sulfate sodium or 2,4 dinitrobenzensulfonic acid.nnnCONCLUSIONSnIn mice, TLR2 signaling regulates intestinal inflammation by controlling ENS structure and neurochemical coding, along with intestinal neuromuscular function. These findings provide information as to how defective TLR2 signaling in the ENS affects inflammatory bowel disease phenotype in humans.

Trophic factors in the carotid body.

The aim of the present study is to provide a review of the expression and action of trophic factors in the carotid body. In glomic type I cells, the following factors have been identified: brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, artemin, ciliary neurotrophic factor, insulin-like growth factors-I and -II, basic fibroblast growth factor, epidermal growth factor, transforming growth factor-alpha and -beta1, interleukin-1beta and -6, tumour necrosis factor-alpha, vascular endothelial growth factor, and endothelin-1 (ET-1). Growth factor receptors in the above cells include p75LNGFR, TrkA, TrkB, RET, GDNF family receptors alpha1-3, gp130, IL-6Ralpha, EGFR, FGFR1, IL1-RI, TNF-RI, VEGFR-1 and -2, ETA and ETB receptors, and PDGFR-alpha. Differential local expression of growth factors and corresponding receptors plays a role in pre- and postnatal development of the carotid body. Their local actions contribute toward producing the morphologic and molecular changes associated with chronic hypoxia and/or hypertension, such as cellular hyperplasia, extracellular matrix expansion, changes in channel densities, and neurotransmitter patterns. Neurotrophic factor production is also considered to play a key role in the therapeutic effects of intracerebral carotid body grafts in Parkinsons disease. Future research should also focus on trophic actions on carotid body type I cells by peptide neuromodulators, which are known to be present in the carotid body and to show trophic effects on other cell populations, that is, angiotensin II, adrenomedullin, bombesin, calcitonin, calcitonin gene-related peptide, cholecystokinin, erythropoietin, galanin, opioids, pituitary adenylate cyclase-activating polypeptide, atrial natriuretic peptide, somatostatin, tachykinins, neuropeptide Y, neurotensin, and vasoactive intestinal peptide.

WU and KI Polyomaviruses in the Brains of HIV-Positive Patients With and Without Progressive Multifocal Leukoencephalopathy

The polyomaviruses KI (KIPyV) and WU (WUPyV) were recently identified mainly in respiratory samples from children and immunosuppressed patients. Investigation of 54 autopsy brain tissue samples from 22 subjects demonstrated that WUPyV DNA and KIPyV DNA could be detected in 1 of 4 human immunodeficiency virus (HIV)-positive individuals with progressive multifocal leukoencephalopathy (PML) and in 3 of 10 HIV-positive individuals without PML, but not in 8 HIV-negative individuals. Viruses were localized in all regions of the central nervous system that were analyzed, that is, the cerebral hemispheres, cerebellum, pons, and medulla oblongata. No specific histopathological findings were found to be associated with the presence of WUPyV and KIPyV.

Varicocele is associated with an increase of connective tissue of the pampiniform plexus vein wall

ObjectiveThe purpose of this study is to describe the normal structure of spermatic vein wall and the morphological alterations in patients with grades 1–3 varicocele.MethodsWe dissected and analyzed a 2–3xa0cm tract of a pampiniform plexus vein of 30 patients undergoing antegrade scrotal sclerotherapy for left varicocele and of 13 consecutive patients undergoing radical orchidectomy for left testis cancer. The histological and morphological examination was performed with hematoxylin–eosin and Azan–Mallory staining through a computer image analysis approach. Vasa vasorum number was evaluated through the anti-CD31 monoclonal antibody.ResultsIn normal veins, the tunica media had a circular smooth muscle layer, the tunica adventitia a longitudinal one; oblique fibers connected the longitudinal with the circular layer. In grade 1 varicocele, we found an increase in the connective tissue of the adventitia (39 vs. 1%, Pxa0<xa00.001) and of the tunica media (13 vs. 0.5%, Pxa0=xa00.001) and a decrease of oblique fibers. In grade 2 varicocele, the adventitia and media showed greater connective tissue (40 and 15%, Pxa0<xa00.001). In grade 3 varicocele, adventitia and media showed a further increase in connective tissue (52 and 28%, respectively, <0.001). No oblique fibers were found in these veins. Vasa vasorum were decreased in number in patients with grades I and II varicocele, and were absent in patients with grade III varicocele.ConclusionThe wall of pampiniform plexus veins is a complex structure. Varicocele induces a decrease of vasa vasorum number, a fibrotic degeneration of the adventitia and media, and a decrease of the oblique running fibers.

The triangles of Grynfeltt and Petit and the lumbar tunnel: an anatomo-radiologic study

PurposeLumbar hernias are protrusions of intra-abdominal contents classically through the superior (Grynfeltt) and inferior (Petit) lumbar triangles. The anatomy of the triangles is variable and quantitative data are few. No radiological data on the anatomy of the triangles are available.MethodsFifty computed tomography angiography of the upper abdomen (M25, F25, mean age 72.5-year-old) were analyzed. The dimensions and the contents of the lumbar triangles were analyzed. The characteristics of the space between the two triangles were also documented.ResultsThe superior lumbar triangle showed a mean surface area of 5.10xa0±xa02.6xa0cm2. In the area of the triangle, the 12th intercostal pedicle and the 1st lumbar branches of the iliolumbar vessels were found in 42 and 46xa0%, respectively. The inferior lumbar triangle had a mean surface of area 18.7xa0±xa08.4xa0cm2. In this area, the 2nd, 3rd, and 4th lumbar branches were found in 9, 67, and 8xa0%, respectively. On oblique coronal images, a direct tunnel between the superior and the inferior lumbar triangles was found, showing an oblique course, with a postero-anterior direction (mean length 36.5xa0±xa05.8xa0mm, mean caliber 7.4xa0±xa03.1xa0mm).ConclusionsAmong the anatomical factors of weakening of the abdominal wall, the course of branches of the lumbar vessels was documented not only in the superior but also in the inferior lumbar triangle. A real musculoaponeurotic tunnel between the superior and the inferior lumbar triangles located in the oblique coronal plane was found, that could play a role in the development of incarceration or strangulation of lumbar hernias.

Transanal ileoproctostomy is feasible in human cadavers

An ileorectal bypass performed entirely through a transanal route has recently been described in an animal model. The present study aimed to demonstrate its technical feasibility in four human cadavers.

Roux-en-Y gastrojejunal bypass using a hybrid NOTES-12 mm trocar technique in a porcine model.

Abstract Aims To evaluate the feasibility and safety of Roux-en-Y gastrojejunal bypass procedure using a hybrid NOTES-12u2009mm trocar technique in a survival porcine model. Material and methods The procedure was carried out on ten pigs. Two gastroscopes were introduced through the mouth and through a 12u2009mm trocar, respectively. A mechanical circular gastro-jejunal anastomosis was created by introducing a stapler after the trocar incision was enlarged. A 21u2009mm EEA OrVil circular stapler was utilized in the first six pigs and a 25u2009mm one was used in the other four. All pigs were fed beginning 24 hours after the procedure and were euthanized three weeks later. Results The procedure was successfully completed in all ten animals. The mean length of the skin incision was 2.5u2009cm. All pigs survived without complications. Endoscopic inspection detected anastomotic strictures in 5/6 of the 21u2009mm-stapler and in 0/4 of the 25u2009mm-stapler anastomoses (u2009pu2009<u20090.05). Conclusion Roux-en-Y gastrojejunal bypass using a hybrid NOTES-single 12u2009mm trocar access technique is a simple and safe procedure in a survival porcine model. Functional results need to be evaluated by further studies.

Urotensin II Exerts Pressor Effects By Stimulating Renin And Aldosterone Synthase Gene Expression

We investigated the in vivo pressor effects of the potent vasoconstrictor Urotensin II (UII). We randomized normotensive Sprague-Dawley rats into 4 groups that received a 7-day UII infusion (cases) or vehicle (controls). Group 1 received normal sodium intake; Group 2 underwent unilateral nephrectomy and salt loading; Group 3 received spironolactone, besides unilateral nephrectomy and salt loading; Group 4 only received spironolactone. UII raised BP transiently after a lag phase of 12-36u2009hours in Group 1, and progressively over the week in Group 2. Spironolactone did not affect blood pressure, but abolished both pressor effects of UII in Group 3, and left blood pressure unaffected in Group 4. UII increased by 7-fold the renal expression of renin in Group 2, increased aldosterone synthase expression in the adrenocortical zona glomerulosa, and prevented the blunting of renin expression induced by high salt. UII raises BP transiently when sodium intake and renal function are normal, but progressively in salt-loaded uninephrectomized rats. Moreover, it increases aldosterone synthase and counteracts the suppression of renin induced by salt loading. This novel action of UII in the regulation of renin and aldosterone synthesis could play a role in several clinical conditions where UII levels are up-regulated.

Tullio Terni (1888–1946): The “column” of spinal cardiovascular regulation

Tullio Terni (1888–1946) was a brilliant anatomist in the School of Medicine of Padova, Italy. He was a versatile scientist who gave fundamental and pioneering contributions in descriptive and experimental cytology, human and comparative morphogenesis, neuroanatomy, embryology and teratology, and regenerative biology. His most famous discovery, which bears his name, is the so‐called “Ternis column.” In embryos of chickens, he described the existence in the thoracolumbar region of the spinal cord of a preganglionic nervous center, constituting a longitudinal column of nervous cells between the first thoracic and the second lumbar segments. Tullio Terni embodied the ideal of free science without geographic boundaries. He used cutting‐edge tools, demonstrating his very current approach. Terni studied the organization of tissues and organs and the spatial arrangement and the physical state of the tissues of living systems. He also practiced experimental embryology, which formed the basis of modern techniques in organ transplantation. Moreover, he studied multiple species in order to compare multiple organisms. Terni was a multifaceted scientist. Clin. Anat. 26:544–546, 2013.