Two-Dimensional Supersolid Formation in Dipolar Condensates.

Dipolar condensates have recently been coaxed to form the long-sought supersolid phase. While one-dimensional supersolids may be prepared by triggering a roton instability, we find that such a procedure in two dimensions (2D) leads to a loss of both global phase coherence and crystalline order. Unlike in 1D, the 2D roton modes have little in common with the supersolid configuration. We develop a finite-temperature stochastic Gross-Pitaevskii theory that includes beyond-mean-field effects to explore the formation process in 2D and find that evaporative cooling directly into the supersolid phase-hence bypassing the first-order roton instability-can produce a robust supersolid in a circular trap. Importantly, the resulting supersolid is stable at the final nonzero temperature. We then experimentally produce a 2D supersolid in a near-circular trap through such an evaporative procedure. Our work provides insight into the process of supersolid formation in 2D and defines a realistic path to the formation of large two-dimensional supersolid arrays.

New High-Confinement Regime with Fast Ions in the Core of Fusion Plasmas.

The key result of the present work is the theoretical prediction and observation of the formation of a new type of transport barrier in fusion plasmas, called F-ATB (fast ion-induced anomalous transport barrier). As demonstrated through state-of-the-art global electrostatic and electromagnetic simulations, the F-ATB is characterized by a full suppression of the turbulent transport-caused by strongly sheared, axisymmetric E×B flows-and an increase of the neoclassical counterpart, albeit keeping the overall fluxes at significantly reduced levels. The trigger mechanism is shown to be a mainly electrostatic resonant interaction between suprathermal particles, generated via ion-cyclotron-resonance heating, and plasma microturbulence. These findings are obtained by realistic simulations of the ASDEX Upgrade discharge No. 36637-properly designed to maximized the beneficial role of the wave-particle resonance interaction-which exhibits the expected properties of improved confinement produced by energetic particles.

Acquired cow's milk sensitization after liver transplant in an adult: "clinical implications" and future strategies.

BACKGROUND: Identifying the mechanisms responsible for the development of food allergy in liver transplant recipients is more complex as there are several different clinical scenarios related to the immunological function of the liver. CASE PRESENTATION: We describe the first case of Transplant Acquired Food Allergy (TAFA) to cow milk in an adult following LT from a donor dead because of anaphylactic shock. A 67-year-old woman with primary biliary cirrhosis was referred to the Transplant Center of our hospital because of an acute-on-chronic liver failure. The donor was a 15-year-old girl deceased for anoxic encephalopathy due to food induced anaphylaxis after eating a biscuit. In the donor's history food allergies to cow milk and eggs were present. CONCLUSION: This case emphasizes the need for a standardized assessment of both solid-organ donors and recipients including donor allergy history in order to detect recipients at risk for anaphylaxis due to passive IgE transfer. Despite several reports of TAFA after solid organ, especially liver, an appropriate protocol to avoid risk for the recipient doesn't exist at the moment. The SPT (skin prick test) or specific IgE level are not enough to ensure a correct management in these cases and a correct education of the patients and the medical staff involved is absolutely necessary. It is the first case of milk allergy sensitization after solid organ transplant by passive transfer of IgE.

Millimeter-Wave Beam Scattering by Field-Aligned Blobs in Simple Magnetized Toroidal Plasmas.

The first direct experimental measurements of the scattering of a millimeter-wave beam by plasma blobs in a simple magnetized torus are reported. The wavelength of the beam is comparable to the characteristic size of the blob. In situ Langmuir probe measurements show that fluctuations of the electron density induce correlated fluctuations of the transmitted power. A first-principles full-wave model, using conditionally sampled 2D electron density profiles, predicts fluctuations of the millimeter-wave power that are in agreement with experiments.

Effects of selective α2 -adrenergic receptor agonists on electrical field-stimulated contractions of isolated bronchi in horses.

We investigated the effects of different selective α2 -adrenergic receptor (AR) agonists (detomidine, medetomidine, xylazine, and brimonidine) on the contractions of horse-isolated bronchi induced by electrical field stimulation (EFS) and by carbachol. No effects were observed on the contraction induced by carbachol, while α2 -AR agonists reduced EFS-evoked contractions in a concentration-related fashion. The rank order of potency (pD2 ) was brimonidine (7.40 ± 0.20) >medetomidine (7.09 ± 0.24) >detomidine (6.13 ± 0.55) >xylazine (4.59 ± 0.16). The maximal effects (Emax ) were -56.3% ± 6.3%, -40.4% ± 6.9%, -48.6% ± 9.9%, and -72.7% ± 12.7% for brimonidine, medetomidine, detomidine, and xylazine, respectively. Adrenergic block by guanethidine enhanced the potency (8.10 ± 0.05, 7.30 ± 0.15, 6.83 ± 0.41, and 5.40 ± 0.22) and the efficacy (-95.2% ± 0.7%, -45.2% ± 11.7%, -58.5% ± 9.8%, and -97.9% ± 0.6%) of brimonidine, medetomidine, detomidine, and xylazine, respectively. Selective α2 -AR antagonist, atipamezole, competitively antagonized the inhibition of EFS-evoked contractions induced by all agonists except xylazine. These results suggest the existence of presynaptic α2 -ARs on cholinergic neurons, negatively regulating the release of acetylcholine in horse bronchial muscle, and that α2 -AR agonists may be beneficial against vagally mediated bronchoconstriction.

Rectus abdominis atrophy after ventral abdominal incisions: midline versus chevron.

PURPOSE: Although many outcomes have been compared between a midline and chevron incision, this is the first study to examine rectus abdominis atrophy after these two types of incisions. METHODS: Patients undergoing open pancreaticobiliary surgery between 2007 and 2011 at our single institution were included in this study. Rectus abdominis muscle thickness was measured on both preoperative and follow-up computed tomography (CT) scans to calculate percent atrophy of the muscle after surgery. RESULTS: At average follow-up of 24.5 and 19.0 months, respectively, rectus abdominis atrophy was 18.9% greater in the chevron (n = 30) than in the midline (n = 180) group (21.8 vs. 2.9%, p < 0.0001). Half the patients with a chevron incision had >20% atrophy at follow-up compared with 10% with a midline incision [odds ratio (OR) 9.0, p < 0.0001]. No significant difference was observed in incisional hernia rates or wound infections between groups. CONCLUSION: In this study, chevron incisions resulted in seven times more atrophy of the rectus abdominis compared with midline incisions. The long-term effects of transecting the rectus abdominis and disrupting its innervation creates challenging abdominal wall pathology. Atrophy of the abdominal wall can not be readily fixed with an operation, and this significant side effect of a transverse incision should be factored into the surgeon's decision-making process when choosing a transverse over a midline incision.

Sildenafil improves clinical signs and radiographic features in dogs with congenital idiopathic megaoesophagus: a randomised controlled trial.

We evaluated the efficacy of oral sildenafil citrate in dogs with congenital idiopathic megaoesophagus (CIM). Twenty-one puppies were randomly assigned to two groups (treatment and control). The dogs were given sildenafil oral suspension 1 mg/kg every 12 hours for 14 days or placebo in a masked fashion. Clinical signs (frequency of regurgitation and weight gain) and oesophagrams (relative oesophageal diameter, ROD) were evaluated in order to assess the efficacy of drug treatment, by examiners who were unaware of the study protocol. In addition, a set of in vitro experiments on isolated samples of canine lower oesophageal sphincter (LOS) was performed, and the effects of increasing concentrations of sildenafil on basal tone and electrically-stimulated motility were assessed. Sildenafil administration significantly reduced the number of regurgitation episodes (0.88±1.40 v 2.65±1.56, P<0.0001) and significantly increased weight gain in the treated dogs compared to controls (79.76±28.30 per cent v 53.40±19.30 per cent, P=0.034). ROD values, at the end of the treatment period, were significantly decreased in the sildenafil group, compared to pre-treatment values (0.97±0.19 v 0.24±0.14, P<0.0001), in contrast to control subjects (0.98±0.17 v 1.10±0.25, P=0.480). In accordance with the in vivo findings, sildenafil dose-dependently reduced basal tone and increased electrically-induced relaxation of dog LOS samples. These results suggest that sildenafil citrate helps ameliorate clinical and radiographic signs in dogs with CIM by reducing LOS tone, and could represent a novel therapeutic tool for the treatment of this disease.

Global DNA methylation profiling uncovers distinct methylation patterns of protocadherin alpha4 in metastatic and non-metastatic rhabdomyosarcoma.

BACKGROUND: Rhabdomyosarcoma (RMS), which can be classified as embryonal RMS (ERMS) and alveolar RMS (ARMS), represents the most frequent soft tissue sarcoma in the pediatric population; the latter shows greater aggressiveness and metastatic potential with respect to the former. Epigenetic alterations in cancer include DNA methylation changes and histone modifications that influence overall gene expression patterns. Different tumor subtypes are characterized by distinct methylation signatures that could facilitate early disease detection and greater prognostic accuracy. METHODS: A genome-wide approach was used to examine methylation patterns associated with different prognoses, and DNA methylome analysis was carried out using the Agilent Human DNA Methylation platform. The results were validated using bisulfite sequencing and 5-aza-2'deoxycytidine treatment in RMS cell lines. Some in vitro functional studies were also performed to explore the involvement of a target gene in RMS tumor cells. RESULTS: In accordance with the Intergroup Rhabdomyosarcoma Study (IRS) grouping, study results showed that distinct methylation patterns distinguish RMS subgroups and that a cluster of protocadherin genes are hypermethylated in metastatic RMS. Among these, PCDHA4, whose expression was decreased by DNA methylation, emerged as a down-regulated gene in the metastatic samples. As PCDHA4-silenced cells have a significantly higher cell proliferation rate paralleled by higher cell invasiveness, PCDHA4 seems to behave as a tumor suppressor in metastatic RMS. CONCLUSION: Study results demonstrated that DNA methylation patterns distinguish between metastatic and non-metastatic RMS and suggest that epigenetic regulation of specific genes could represent a novel therapeutic target that could enhance the efficiency of RMS treatments.

Stationary Zonal Flows during the Formation of the Edge Transport Barrier in the JET Tokamak.

High spatial resolution Doppler backscattering measurements in JET have enabled new insights into the development of the edge Er. We observe fine-scale spatial structures in the edge Er well with a wave number krρi≈0.4-0.8, consistent with stationary zonal flows, the characteristics of which vary with density. The zonal flow amplitude and wavelength both decrease with local collisionality, such that the zonal flow E×B shear increases. Above the minimum of the L-H transition power threshold dependence on density, the zonal flows are present during L mode and disappear following the H-mode transition, while below the minimum they are reduced below measurable amplitude during L mode, before the L-H transition.

The potential of imogolite nanotubes as (co-)photocatalysts: a linear-scaling density functional theory study.

We report a linear-scaling density functional theory (DFT) study of the structure, wall-polarization absolute band-alignment and optical absorption of several, recently synthesized, open-ended imogolite (Imo) nanotubes (NTs), namely single-walled (SW) aluminosilicate (AlSi), SW aluminogermanate (AlGe), SW methylated aluminosilicate (AlSi-Me), and double-walled (DW) AlGe NTs. Simulations with three different semi-local and dispersion-corrected DFT-functionals reveal that the NT wall-polarization can be increased by nearly a factor of four going from SW-AlSi-Me to DW-AlGe. Absolute vacuum alignment of the NT electronic bands and comparison with those of rutile and anatase TiO2 suggest that the NTs may exhibit marked propensity to both photo-reduction and hole-scavenging. Characterization of the NTs' band-separation and optical properties reveal the occurrence of (near-)UV inside-outside charge-transfer excitations, which may be effective for electron-hole separation and enhanced photocatalytic activity. Finally, the effects of the NTs' wall-polarization on the absolute alignment of electron and hole acceptor states of interacting water (H2O) molecules are quantified and discussed.

Functional and molecular defects of hiPSC-derived neurons from patients with ATM deficiency.

Loss of ataxia telangiectasia mutated (ATM) kinase, a key factor of the DNA damage response (DDR) pathway, causes the cancer predisposing and neurodegenerative syndrome ataxia-telangiectasia (A-T). To investigate the mechanisms of neurodegeneration, we have reprogrammed fibroblasts from ATM-null A-T patients and normal controls to pluripotency (human-induced pluripotent stem cells), and derived from these neural precursor cells able to terminally differentiate into post-mitotic neurons positive to >90% for ß-tubulin III+/microtubule-associated protein 2+. We show that A-T neurons display similar voltage-gated potassium and sodium currents and discharges of action potentials as control neurons, but defective expression of the maturation and synaptic markers SCG10, SYP and PSD95 (postsynaptic density protein 95). A-T neurons exhibited defective repair of DNA double-strand breaks (DSBs) and repressed phosphorylation of ATM substrates (e.g., γH2AX, Smc1-S966, Kap1-S824, Chk2-T68, p53-S15), but normal repair of single-strand breaks, and normal short- and long-patch base excision repair activities. Moreover, A-T neurons were resistant to apoptosis induced by the genotoxic agents camptothecin and trabectedin, but as sensitive as controls to the oxidative agents. Most notably, A-T neurons exhibited abnormal accumulation of topoisomerase 1-DNA covalent complexes (Top1-ccs). These findings reveal that ATM deficiency impairs neuronal maturation, suppresses the response and repair of DNA DSBs, and enhances Top1-cc accumulation. Top1-cc could be a risk factor for neurodegeneration as they may interfere with transcription elongation and promote transcriptional decline.

DHEA pre-treated patients, poor responders to a first IVF (ICSI) cycle: clinical results.

PURPOSE: To evaluate the effect of the premedication with dehydroepiandrosterone (DHEA) on the results of the in vitro fertilization (IVF) treatments in a group of women with evidence of diminished ovarian reserve. MATERIALS AND METHODS: This experimental, prospective, pre-post study enrolled 29 patients with evidence of diminished ovarian reserve and poor-responders to a previous treatment. They received 75 mg/die of DHEA for a minimum of eight weeks; from the 18th day of the cycle before the stimulation with follicle stimulating hormone (FSH), they took trans-dermal estradiol (E2) (50 mcg every other day). The protocol of the stimulation consisted of a short cycle with follicle stimulating hormone receptor-human menopausal gonadrotropin (FSHr-HMG) and low doses ofgonadotropin releasing hormone agonist (GnRH-a) (0.05 mg/die). The study was carried out comparing the results obtained respectively with the pre-DHEA and the post-DHEA treatments. RESULTS: The comparative analysis of the results showed a significant increase in the number of the retrieved oocytes (p < 0.01), of the oocyte quality (p = 0.02) and a reduction of cancelled cycles (p = 0.03). Moreover, after the treatment with DHEA, there was an increase, though non-significant, in the number of embryos, in the fertilization rate, and in the number of pregnancies. CONCLUSIONS: This study confirms the beneficial effects of DHEA in patients who resulted poor responders to IVF treatments. Therefore, DHEA appears to be an effective treatment for age related sub-fertility.

Pharmacological characterization of muscarinic receptors in the contractions of isolated bronchi in the horse.

We investigated the effects of nonselective muscarinic antagonist (atropine) and of selective muscarinic subtype 1 (M1), 2 (M2), 3 (M3) antagonists (VU0255035, methoctramine, pFHHSiD, respectively) on the contractions evoked by electrical field stimulation (EFS) or by exogenous ACh in isolated horse bronchial muscle. Atropine completely inhibited neurogenic contractions in a concentration-dependent fashion, whereas selective muscarinic antagonists induced relevant modifications only at the highest concentration tested. Experiments with selective muscarinic antagonists in combination showed that only the simultaneous blockade of M1 /M3 or M2 /M3 receptors was able to induce a nearly complete suppression of contractions. The contractions induced by exogenous ACh were competitively antagonized only by atropine (pA2 = 9.01 ± 0.05). M3 selective antagonist, up to 10(-6) m, caused a moderate concentration-dependent rightward shift of ACh curve (pA2 = 7.96 ± 0.10). These data show that M3 muscarinic receptors possess a central role in mediating cholinergic contraction of horse bronchi, while M1 and M2 receptors seem to have a cooperative role. Selective muscarinic antagonists seem unlikely to be useful against bronchoconstriction associated with airway diseases in horses. Conversely, compounds with selectivity for both M1 and M3 receptors could be as effective as traditional anticholinergics and induce fewer cardiac side effects.

Murine neural stem cells model Hunter disease in vitro: glial cell-mediated neurodegeneration as a possible mechanism involved.

Mucopolysaccharidosis type II (MPSII or Hunter Syndrome) is a lysosomal storage disorder caused by the deficit of iduronate 2-sulfatase (IDS) activity and characterized by progressive systemic and neurological impairment. As the early mechanisms leading to neuronal degeneration remain elusive, we chose to examine the properties of neural stem cells (NSCs) isolated from an animal model of the disease in order to evaluate whether their neurogenic potential could be used to recapitulate the early phases of neurogenesis in the brain of Hunter disease patients. Experiments here reported show that NSCs derived from the subventricular zone (SVZ) of early symptomatic IDS-knockout (IDS-ko) mouse retained self-renewal capacity in vitro, but differentiated earlier than wild-type (wt) cells, displaying an evident lysosomal aggregation in oligodendroglial and astroglial cells. Consistently, the SVZ of IDS-ko mice appeared similar to the wt SVZ, whereas the cortex and striatum presented a disorganized neuronal pattern together with a significant increase of glial apoptotic cells, suggesting that glial degeneration likely precedes neuronal demise. Interestingly, a very similar pattern was observed in the brain cortex of a Hunter patient. These observations both in vitro, in our model, and in vivo suggest that IDS deficit seems to affect the late phases of neurogenesis and/or the survival of mature cells rather than NSC self-renewal. In particular, platelet-derived growth factor receptor-α-positive (PDGFR-α+) glial progenitors appeared reduced in both the IDS-ko NSCs and in the IDS-ko mouse and human Hunter brains, compared with the respective healthy controls. Treatment of mutant NSCs with IDS or PDGF throughout differentiation was able to increase the number of PDGFR-α+ cells and to reduce that of apoptotic cells to levels comparable to wt. This evidence supports IDS-ko NSCs as a reliable in vitro model of the disease, and suggests the rescue of PDGFR-α+ glial cells as a therapeutic strategy to prevent neuronal degeneration.

Inhibition of motility in isolated horse small intestine is mediated by κ but not µ opioid receptors.

The effects of preferential µ (morphine), selective µ (fentanyl), selective κ (compound U69593) opioid receptor agonists, and nonselective (naloxone) and selective µ (naloxonazine) antagonists on equine small intestinal motility were evaluated in vitro. Samples of circular muscle from equine jejunum were placed in isolated organ baths and drug-induced modifications of both spontaneous and electrically evoked contractile activity were measured. None of the opioid agonists induced a significant change in spontaneous contractions. Fentanyl and U69593 reduced electrically induced contractions, whereas morphine reduced them only slightly. Naloxone competitively antagonised U69593, but both naloxone and naloxonazine were unable to counteract the inhibition of contractions induced by fentanyl. The inhibition of contractions shown by fentanyl is therefore probably not mediated by opioid receptors, but due to an anticholinergic activity of this drug. In summary, these data showed an inhibitory effect exerted by κ receptors on equine small intestinal motility, whereas the role of µ receptors seemed marginal and would need further characterisation.

Patients with profuse hair shedding may reveal anagen hair dystrophy: a diagnostic clue of alopecia areata incognita.

BACKGROUND: Several patients, especially women, seek advice because of hair loss. They may be diagnosed clinically as having telogen effluvium (TE) or androgenetic alopecia (AGA), but histopathology may reveal that a proportion of them have in fact alopecia areata incognita (AAI). OBJECTIVES: To detect dystrophic anagen hairs in such patients. METHODS: We studied 1932 patients with hair loss and no signs of classical alopecia areata. They were submitted to the modified wash test (which counts the total number of telogen hairs lost and the percentage of vellus hairs) and divided into patients having pure TE (403), patients with AGA+TE (1235) and patients with pure AGA (294). Dystrophic hairs were detected with a low magnification microscope. RESULTS: Dystrophic hairs were observed in 13 patients with TE (3.2%), in 54 with AGA+TE (4.4%) and in none with AGA. In addition, 7 patients with TE and 32 with AGA+TE developed small patches of alopecia areata in 6 to 9 weeks. No patches developed in patients with AGA. CONCLUSIONS: The presence of dystrophic hairs and the development of patches of alopecia areata (and their absence in pure AGA) provide a first evidence of the possibility that within the heterogenous condition named TE some patients have in fact AAI.

Combined cardiac surgery and total thyroidectomy: our experience and review of the literature.

BACKGROUND: The prevalence of thyroid disease in patients with cardiac disease can be as high as 11.2%. Combined thyroid and cardiovascular surgery has rarely been reported. METHODS: Ten patients (6 female, 4 male, age range 51-73 years) had total thyroidectomy and cardiac surgery in the same procedure in our surgical department. Six patients had coronary artery disease; four patients had valvulopathy. The thyroid goiter was retrosternal in 6 patients. RESULTS: Mean stay in the intensive care unit was 46.4 hours; the postoperative course was complicated by transient right laryngeal nerve palsy in one case and by transient hypocalcemia in the patients in whom a parathyroid autotransplantation was performed (n = 3). There was one case of hemodynamic compromise needing vasoactive drug support; the mean hospital stay was 8.4 days. CONCLUSIONS: Our experience and our review of the literature suggest that a single-stage procedure is safe and feasible and must be preferred to different operations as it has an acceptable peri-operative and anesthesiological risk.

Effects of oral curcumin on indomethacin-induced small intestinal damage in the rat.

Nonsteroidal anti-inflammatory drug (NSAID)-induced injury on gastrointestinal tract is well documented, and jejunal inflammation caused by indomethacin in rats is a broadly used experimental model of enteritis. We evaluated the effect of oral curcumin, a compound known to possess anti-inflammatory and anti-oxidant properties, on indomethacin-induced enteritis in the rat. Curcumin (50, 100, and 300 mg/kg) was given to rats by oral gavage 48, 24, and 1 h before enteritis was induced by intragastric administration of 20 mg/kg indomethacin. After 24 h, intestinal macroscopic lesions, myeloperoxidase activity and lipid peroxidation levels were assessed. Curcumin at the dose of 50 mg/kg was uneffective, while at the dose of 100 and 300 mg/kg significantly reduced macroscopic damage caused by indomethacin. By contrast, curcumin at all tested doses was unable to modify indomethacin-induced increases of myeloperoxidase and lipid peroxidation. Curcumin (100 and 300 mg/kg) significantly increased lipid peroxidation level in normal intestinal tissues of rats. Present data show that oral curcumin protects against macroscopic injury induced by indomethacin, leaving unaffected neutrophil infiltration and oxidative cell damage, thus suggesting that this beneficial effect is due to mechanisms not involving anti-inflammatory or antioxidant activities.

Effects of nonselective and selective cyclooxygenase inhibitors on small intestinal motility in the horse.

We investigated the effects of nonselective cyclooxygenase (COX) inhibitors (indomethacin and flunixin meglumine) and selective COX-1 (SC-560) or COX-2 (celecoxib, DUP-398 and NS-697) inhibitors on horse small bowel motility in vitro. At this purpose, samples of equine ileum were put in isolated organ baths for the motility experiments. Nonselective COX inhibitors were devoid of major effects on motility, except for an inhibition of tonic contraction shown by flunixin meglumine. SC-560, selective COX-1 inhibitor, was devoid of significant effects on ileal motility. Selective COX-2 inhibitors reduced both tonic contraction and spontaneous phasic contractions, while prostaglandin (PG) receptor antagonists were uneffective. Some of the intestinal samples were submitted to histological investigation or reverse transcription-polymerase chain reaction (RT-PCR), which revealed the presence of an inflammation reaction and the presence of both COX isoforms mRNAs. Present data support the hypothesis that the effects of COX inhibitors on horse small intestinal motility are not linked to PG depletion.

Long-term study of TNBS-induced colitis in rats: focus on mast cells.

OBJECTIVE AND DESIGN: To investigate the severity and duration of colitis induced by two different doses of 2,4,6-trinitrobenzenesulfonic acid (TNBS) and the changes in mast cell number in acute inflammation and in the recovery process of colitis. METHODS: Colitis was induced in rats by an enema of TNBS (10 or 30 mg) in 25% ethanol. Macroscopic and histologic changes of the colon, colon weight and mast cell counts were examined at various times (7, 30 and 60 days) after colitis induction. RESULTS: TNBS induced a colonic damage which was dose-related for both severity and time necessary to complete recovery. On day 7 after colitis induction 10 mg TNBS induced macroscopic and microscopic alterations of colonic architecture that completely resolved at day 60. By contrast, 30 mg TNBS induced massive necrosis, thickening of the colon, severe histologic changes that were only partially reversed after two months. Mast cell number in the submucosa and muscularis propria decreased significantly in the acute phase of inflammation (7 days) and slowly increased thereafter, reaching a maximum level (up to about 5-fold) at day 60 after both doses of TNBS. CONCLUSIONS: Present data confirm the ability of TNBS to induce in rats damage to the colon that was dose-dependent for severity and duration. Moreover, these data unravel a different role of mast cells in TNBS-induced colitis: an early degranulation in the acute phase of inflammation and a subsequent accumulation of mast cells in the late phase of the disease, associated with tissue repair.