New insights to occult gastrointestinal bleeding: From pathophysiology to therapeutics.

Obscure gastrointestinal bleeding is still a clinical challenge for gastroenterologists. The recent development of novel technologies for the diagnosis and treatment of different bleeding causes has allowed a better management of patients, but it also determines the need of a deeper comprehension of pathophysiology and the analysis of local expertise in order to develop a rational management algorithm. Obscure gastrointestinal bleeding can be divided in occult, when a positive occult blood fecal test is the main manifestation, and overt, when external sings of bleeding are visible. In this paper we are going to focus on overt gastrointestinal bleeding, describing the physiopathology of the most usual causes, analyzing the diagnostic procedures available, from the most classical to the novel ones, and establishing a standard algorithm which can be adapted depending on the local expertise or availability. Finally, we will review the main therapeutic options for this complex and not so uncommon clinical problem.

Dynamic regulation of notch 1 and notch 2 surface expression during T cell development and activation revealed by novel monoclonal antibodies.

It is well established that Notch signaling plays a critical role at multiple stages of T cell development and activation. However, detailed analysis of the cellular and molecular events associated with Notch signaling in T cells is hampered by the lack of reagents that can unambiguously measure cell surface Notch receptor expression. Using novel rat mAbs directed against the extracellular domains of Notch1 and Notch2, we find that Notch1 is already highly expressed on common lymphoid precursors in the bone marrow and remains at high levels during intrathymic maturation of CD4(-)CD8(-) thymocytes. Notch1 is progressively down-regulated at the CD4(+)CD8(+) and mature CD4(+) or CD8(+) thymic stages and is expressed at low levels on peripheral T cells. Immunofluorescence staining of thymus cryosections further revealed a localization of Notch1(+)CD25(-) cells adjacent to the thymus capsule. Notch1 was up-regulated on peripheral T cells following activation in vitro with anti-CD3 mAbs or infection in vivo with lymphocytic chorio-meningitis virus or Leishmania major. In contrast to Notch1, Notch2 was expressed at intermediate levels on common lymphoid precursors and CD117(+) early intrathymic subsets, but disappeared completely at subsequent stages of T cell development. However, transient up-regulation of Notch2 was also observed on peripheral T cells following anti-CD3 stimulation. Collectively our novel mAbs reveal a dynamic regulation of Notch1 and Notch2 surface expression during T cell development and activation. Furthermore they provide an important resource for future analysis of Notch receptors in various tissues including the hematopoietic system.

The occurrence of reptiles in Barn Owl diet in Europe

Capsule We present a review of the propensity to eat reptiles in the Barn Owl Tyto alba in Europe. Based on the analysis of 591 published studies reporting 3.07 million prey items identified in pellets, only 2402 reptiles (0.08%) were found. Reptiles were most often captured in southern parts of the European continent and on islands. A large proportion of the 1304 identified reptiles to the species level were nocturnal Gekkonidae (77.1%).

Neuroprotective gene therapy for Huntington's disease, using polymer-encapsulated cells engineered to secrete human ciliary neurotrophic factor: results of a phase I study.

Huntington's disease (HD) is a monogenic neurodegenerative disease that affects the efferent neurons of the striatum. The protracted evolution of the pathology over 15 to 20 years, after clinical onset in adulthood, underscores the potential of therapeutic tools that would aim at protecting striatal neurons. Proteins with neuroprotective effects in the adult brain have been identified, among them ciliary neurotrophic factor (CNTF), which protected striatal neurons in animal models of HD. Accordingly, we have carried out a phase I study evaluating the safety of intracerebral administration of this protein in subjects with HD, using a device formed by a semipermeable membrane encapsulating a BHK cell line engineered to synthesize CNTF. Six subjects with stage 1 or 2 HD had one capsule implanted into the right lateral ventricle; the capsule was retrieved and exchanged for a new one every 6 months, over a total period of 2 years. No sign of CNTF-induced toxicity was observed; however, depression occurred in three subjects after removal of the last capsule, which may have correlated with the lack of any future therapeutic option. All retrieved capsules were intact but contained variable numbers of surviving cells, and CNTF release was low in 13 of 24 cases. Improvements in electrophysiological results were observed, and were correlated with capsules releasing the largest amount of CNTF. This phase I study shows the safety, feasibility, and tolerability of this gene therapy procedure. Heterogeneous cell survival, however, stresses the need for improving the technique.

Cytotoxic effects of FGF2-saporin on bovine epithelial lens cells in vitro.

PURPOSE: To test the ability of two preparations of FGF2-saporin, either FGF2 chemically conjugated to saporin (FGF2-SAP) or genetically engineered FGF2-saporin (rFGF2-SAP) to inhibit the growth of bovine epithelial lens (BEL) cells in vitro when in solution and when immobilized on heparin surface-modified (HSM) polymethylmethacrylate (PMMA) intraocular lenses (IOLs). METHOD: Bovine epithelial lens cells were incubated with various concentrations FGF2-saporin for as long as 4 days. The number of surviving cells was determined by counting the number of nuclei. Because FGF2 binds to heparin, FGF2-saporin was incubated with HSM PMMA IOLs; excess toxin was washed off, and the BEL cells were grown on the FGF2-saporin-treated IOLs (HSM and non-HSM) for 4 days. Cell density was determined by image analysis. RESULTS: Both FGF2-SAP and rFGF2-SAP were highly cytotoxic (nM range), with rFGF2-SAP 10 times less active than FGF2-SAP. FGF2-saporin bound to the surface of HSM IOLs and eluted by 2M NaCl retained its activity. Toxin bound to HSM IOLs killed more than 90% of the BEL cells placed on the IOL surface within 4 days. The ability of FGF2-saporin to prevent the growth of cells on the IOL surface was strictly dependent on the presence of heparin on the IOL. CONCLUSIONS: FGF2-saporin is bound to HSM PMMA IOLs and prevents the growth of epithelial cells on the surface of the lens.

Primary activity measurements with a 4πβ-4πγ coincidence counting system.

The radioactive concentrations of (166m)Ho, (134)Cs and (133)Ba solutions have been standardised using a 4πβ-4πγ coincidence counting system we have recently set up. The detection in the beta channel is performed using various geometries of a UPS-89 plastic scintillator optically coupled to a selected low-noise 1in. diameter photomultiplier tube. The light-tight thin capsule that encloses this beta detector is housed within the well of a 5in.×5in. NaI(Tl) monocrystal detector. The beta detection efficiency can be varied either by optical filtering or electronic discrimination when the electrons loose all their energy in the plastic scintillator. This 4πβ-4πγ coincidence system improves on our 4πβ(PC)-γ system in that its sample preparation is less labour intensive, it yields larger beta- and gamma-counting efficiencies thus enabling the standardisation of low activity sources with good statistics in reasonable time, and it makes standardising short-lived radionuclides easier. The resulting radioactive concentrations of (166m)Ho, (134)Cs and (133)Ba are found to agree with those measured with other primary measurement methods thus validating our 4πβ-4πγ coincidence counting system.

Imaging pheromone sensing in a mouse vomeronasal acute tissue slice preparation.

Peter Karlson and Martin Lüscher used the term pheromone for the first time in 1959 to describe chemicals used for intra-species communication. Pheromones are volatile or non-volatile short-lived molecules secreted and/or contained in biological fluids, such as urine, a liquid known to be a main source of pheromones. Pheromonal communication is implicated in a variety of key animal modalities such as kin interactions, hierarchical organisations and sexual interactions and are consequently directly correlated with the survival of a given species. In mice, the ability to detect pheromones is principally mediated by the vomeronasal organ (VNO), a paired structure located at the base of the nasal cavity, and enclosed in a cartilaginous capsule. Each VNO has a tubular shape with a lumen allowing the contact with the external chemical world. The sensory neuroepithelium is principally composed of vomeronasal bipolar sensory neurons (VSNs). Each VSN extends a single dendrite to the lumen ending in a large dendritic knob bearing up to 100 microvilli implicated in chemical detection. Numerous subpopulations of VSNs are present. They are differentiated by the chemoreceptor they express and thus possibly by the ligand(s) they recognize. Two main vomeronasal receptor families, V1Rs and V2Rs, are composed respectively by 240 and 120 members and are expressed in separate layers of the neuroepithelium. Olfactory receptors (ORs) and formyl peptide receptors (FPRs) are also expressed in VSNs. Whether or not these neuronal subpopulations use the same downstream signalling pathway for sensing pheromones is unknown. Despite a major role played by a calcium-permeable channel (TRPC2) present in the microvilli of mature neurons TRPC2 independent transduction channels have been suggested. Due to the high number of neuronal subpopulations and the peculiar morphology of the organ, pharmacological and physiological investigations of the signalling elements present in the VNO are complex. Here, we present an acute tissue slice preparation of the mouse VNO for performing calcium imaging investigations. This physiological approach allows observations, in the natural environment of a living tissue, of general or individual subpopulations of VSNs previously loaded with Fura-2AM, a calcium dye. This method is also convenient for studying any GFP-tagged pheromone receptor and is adaptable for the use of other fluorescent calcium probes. As an example, we use here a VG mouse line, in which the translation of the pheromone V1rb2 receptor is linked to the expression of GFP by a polycistronic strategy.

Scar asymmetry after abdominoplasty: the unexpected role of seroma.

Achievement of symmetry remains one of the goals of cosmetic procedures. Interestingly, scar asymmetry after abdominoplasty has been rarely considered a complication. However, this can have a significant impact on patient and surgeon satisfaction. This study identifies silent seromas as a potential cause of scar asymmetry.Among abdominoplasty procedures in a university hospital institution over a 30 months' period (October 1, 2007 to April 1, 2010), we retrospectively identified 6 patients who developed abdominal scar asymmetry only 3 months postoperatively and without any early warning complications (hematoma, seroma, or infection). Clinical examination was completed by abdominal diagnostic ultrasonography. Seroma capsulectomy under local anesthesia was performed in all cases.In all patients clinically presenting late abdominal scar asymmetry, ultrasonography confirmed the presence of an encapsulated chronic seroma. Surgical capsulectomy under local anesthesia resulted in reestablishment of former symmetry and high patient satisfaction. No complications such as wound infection, dehiscence, hematoma, or recurrence of seroma were detected after revision surgery.In our experience, fibrous capsule due to chronic seromas resulted in abdominal scar deviation and asymmetry. Surgical capsulectomy followed by wearing of compressive garments resulted to be an effective treatment with pleasant aesthetic outcome and no seroma recurrence. Silent seromas should be considered as a possible etiologic factor of scar asymmetries appearing during late follow-up after abdominoplasty.

Identification of sap-feeder instars in Angelabella tecomae Vargas & Parra (Lepidoptera, Gracillariidae) feeding on Tecoma fulva fulva (Bignoniaceae)

The number of sap-feeding instars of the leaf-miner Angelabella tecomae Vargas & Parra, 2005 was determined by measuring the head capsule exuviae collected from mines (n = 125) on the shrub Tecoma fulva fulva D. Don (Bignoniaceae) in the Azapa Valley, northern Chile. Sap-feeding larvae went through four instars in 120 occasions while five larvae went through five instars. The possible causes for this variation and the usefulness of this tool for future studies are discussed.

Biological aspects of Leucothyreus ambrosius Blanchard (Coleoptera, Melolonthidae, Rutelinae)

Biological aspects of Leucothyreus ambrosius Blanchard (Coleoptera, Melolonthidae, Rutelinae). Coleopterans of the family Melolonthidae comprise a large group of species that feed on different food sources, including plant roots, stems, and leaves, in addition to plant materials at different decomposition stages. Several species are found in the genus Leucothyreus, occurring in different regions of Brazil, including the various biomes in the country. Information on the biology of species of the genus Leucothyreus is scarce, therefore, we conducted studies on the biological aspects of Leucothyreus ambrosius Blanchard, 1850. The period of adult occurrence was determined with a light trap installed between a cropped and pasture area in the municipality of Aquidauana, Mato Grosso do Sul State, Brazil. Adults collected in the field were used to form insect pairs and the studies were initiated in the entomology laboratory as the adults began ovipositing. Adults were observed flying in the field from October to December. Eggs were obtained as pairs were formed and a colony was established, the embryonic period lasting 14.6 days on average. The larval period in the 1st instar lasted 21.6 days, in the 2nd instar 19.6 days, and in the 3rd instar, 85.6 days. The head capsule width was 1.48 mm in the 1st instar, 2.44 mm in the 2nd, and 3.83 mm in 3rd larval instar. The pupal stage had an average duration of 35.5 days. The egg to adult period lasted 173.3 days. Morphometric information for the larval and adult stages is presented in this study.

Biomass estimation of Triplectides egleri Sattler (Trichoptera, Leptoceridae) in a stream at Ducke Reserve, Central Amazonia

ABSTRACT Biomass is a fundamental measure for understanding the structure and functioning (e.g. fluxes of energy and nutrients in the food chain) of aquatic ecosystems. We aim to provide predictive models to estimate the biomass of Triplectides egleri Sattler, 1963, in a stream in Central Amazonia, based on body and case dimensions. We used body length, head-capsule width, interocular distance and case length and width to derive biomass estimations. Linear, exponential and power regression models were used to assess the relationship between biomass and body or case dimensions. All regression models used in the biomass estimation of T. egleri were significant. The best fit between biomass and body or case dimensions was obtained using the power model, followed by the exponential and linear models. Body length provided the best estimate of biomass. However, the dimensions of sclerotized structures (interocular distance and head-capsule width) also provided good biomass predictions, and may be useful in estimating biomass of preserved and/or damaged material. Case width was the dimension of the case that provided the best estimate of biomass. Despite the low relation, case width may be useful in studies that require low stress on individuals.

Morgagnian cataract simulating iris neoplasia : case report

Purpose: to describe a case in which the diagnosis of Morganian cataract required clinical and instrumental differentiation from iris pathologies, including iris melanoma. Methods: a 60-years-old Caucasian man referred to our institute for worsening of vision in last few months. Clinical evaluation consisted in complete ophthalmological assessment, ultrasound examination (biomicroscopy and 20MHz), and Magnetic Resonance Imaging (MRI) completed with Susceptibility Weighted Imaging (SWI). Results: traumatic corneal wound of the left eye (LE) had occurred 5 years before, and was treated with medical therapy alone. Best-corrected visual acuity (BCVA) was 3/10 in the right eye (RE) and finger count in the LE, with intraocular pressure at 13 and 20mmHg, respectively. Chronic central serous chorioretinopathy, accounted for the low visual acuity of the RE. Slit-lamp biomicroscopy of the LE was as in Figure 1; LE fundus was not clinically observable. Despite MRI was compatible with an iris solid formation, characterized by contrast enhancement and hyperintense signal in SWI, ultrasound indicated rather a mixed solid and liquid content (moderately echogenic external layer, hyporeflective internal content). Iris root and ciliary body were not significantly altered; the lens showed inhomogeneous content. We considered Morgagnian cataract the most probable diagnosis. Surgery confirmed the presence of a hypermature cataract with prior anterior capsule fissuring; the liquefied cortex infiltrated the iris without anterior chamber seeping. Post-operative BCVA was 3/10 and fundus examination disclosed an advanced macular chronic central serous chorioretinopathy. Conclusions: In the reported case a previous perforating trauma have probably damaged the lens capsule and started cataract progression. Curiously cataract developed percolating into the iris stroma, thus simulating an iris mass. At our knowledge, Morgagnian cataract has never been included in the differential diagnosis of iris mass.

n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia.

BACKGROUND: The use of n-3 fatty acids may prevent cardiovascular events in patients with recent myocardial infarction or heart failure. Their effects in patients with (or at risk for) type 2 diabetes mellitus are unknown. METHODS: In this double-blind study with a 2-by-2 factorial design, we randomly assigned 12,536 patients who were at high risk for cardiovascular events and had impaired fasting glucose, impaired glucose tolerance, or diabetes to receive a 1-g capsule containing at least 900 mg (90% or more) of ethyl esters of n-3 fatty acids or placebo daily and to receive either insulin glargine or standard care. The primary outcome was death from cardiovascular causes. The results of the comparison between n-3 fatty acids and placebo are reported here. RESULTS: During a median follow up of 6.2 years, the incidence of the primary outcome was not significantly decreased among patients receiving n-3 fatty acids, as compared with those receiving placebo (574 patients [9.1%] vs. 581 patients [9.3%]; hazard ratio, 0.98; 95% confidence interval [CI], 0.87 to 1.10; P=0.72). The use of n-3 fatty acids also had no significant effect on the rates of major vascular events (1034 patients [16.5%] vs. 1017 patients [16.3%]; hazard ratio, 1.01; 95% CI, 0.93 to 1.10; P=0.81), death from any cause (951 [15.1%] vs. 964 [15.4%]; hazard ratio, 0.98; 95% CI, 0.89 to 1.07; P=0.63), or death from arrhythmia (288 [4.6%] vs. 259 [4.1%]; hazard ratio, 1.10; 95% CI, 0.93 to 1.30; P=0.26). Triglyceride levels were reduced by 14.5 mg per deciliter (0.16 mmol per liter) more among patients receiving n-3 fatty acids than among those receiving placebo (P<0.001), without a significant effect on other lipids. Adverse effects were similar in the two groups. CONCLUSIONS: Daily supplementation with 1 g of n-3 fatty acids did not reduce the rate of cardiovascular events in patients at high risk for cardiovascular events. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.).

Geographic and temporal variation in the consumption of bats by European barn owls

Capsule We report a review of the occurrence of bats in the Barn Owl diet Tyto alba in Europe. Based on 802 studies reporting 4.02 million prey items identified in pellets, 4949 were bats (0.12%). We found that bat predation decreased during the last 150 years, is more frequent on islands than mainland, and is higher in eastern than western Europe and in southern than northern Europe. Although Barn Owls usually capture bats opportunistically, they can sometimes specialize on them.

Cataractogenesis after total body irradiation.

PURPOSE: To evaluate the prognostic factors and the ophthalmologic follow-up on cataract formation following total body irradiation (TBI) prior to bone marrow transplantation (BMT). METHODS AND MATERIALS: Between 1980 and 1992, 494 patients were referred to our department for TBI prior to BMT. The mean age was 32 +/- 11 (median: 32, range: 2-63) years and the male to female ratio was 1.6 (304:190). The majority of patients were treated for acute leukemia (lymphoblastic, n = 177, 36%; or nonlymphoblastic , n = 139, 28%); 80 (16%) for chronic myeloid leukemia, 60 (12%) for non-Hodgkin's lymphoma, 23 (5%) for multiple myeloma, and 15 (3%) for other malignancies. Two hundred and fifty-four (51%) patients were grafted in the first complete remission (CR), 118 (24%) in second CR. Allogenic BMT was performed in 210 (43%) patients, and autologous BMT in 284 (57%). Methotrexate combined to steroids (n = 47, 22%) or to cyclosporine (n = 163, 78%) was administered for graft-versus-host disease (GvHD) prophylaxis. In 188 patients (38%), heparin was used in the prevention of veno-occlusive disease (VOD) of the liver. Furthermore, steroid administration was registered in 223 (45%). The conditioning chemotherapy consisted of cyclophosphamide (Cy) alone in 332 (67%) patients. Total-body irradiation was administered either in single dose (STBI; 10 Gy in 1 day, n = 291) or in six fractions (FTBI; 12 Gy over 3 consecutive days, n = 203) before BMT. The mean instantaneous dose rate was 0.0574 +/- 0.0289 Gy/min (0.024-0.1783). It was < 0.048 Gy/min in 157 patients (LOW group), > or = 0.048 Gy/min and <0.09 Gy/min in 301 patients (MEDIUM group), and > or = 0.09 Gy/min in 36 patients (HIGH group). RESULTS: When considering all patients, 42 (8.5%) patients developed cataracts after 13 to 72 months (median: 42 months) with a 5-year estimated cataract incidence (ECI) of 23%. Thirty-three (11.3%) out of 291 patients in the STBI group, and 9 (4.4%) out of 203 patients in the FTBI group developed cataracts with 5-year estimated incidences of 34 and 11%, respectively (p = 0.0004). Seven (19.4%) out of 36 patients in the HIGH group, 33 (10.9%) out of 301 in the MEDIUM group, and 2 (1.2%) out of 157 in the LOW group developed cataracts with respective 5-year cataract incidences of 54%, 30%, and 3.5% (HIGH vs. MEDIUM, p = 0.07; MEDIUM vs. LOW, p = 0.0001; HIGH vs. LOW, p < 0.0001). On the other hand, patients who received heparin as prophylactic treatment against VOD of the liver had less cataracts than those who did not receive (5-year ECI of 16% vs. 28%, respectively; p = 0.01). There was no statistically significant difference in terms of 5-year ECI according to age, sex, administration of steroids, GvHD prophylaxis, type of BMT, or previous cranial radiotherapy in children. Multivariate analysis revealed that the instantaneous dose rate (p = 0.001), and the administration of heparin against VOD (p = 0.05) were the two independent factors influencing the cataract incidence, while age, fractionation, and use of steroids were not. Among the 42 patients who developed cataracts, 38 had bilateral extracapsular cataract extraction and intraocular lens implantation, and only 4 (10%) developed secondary cataracts in a median follow-up period of 39 months. CONCLUSION: Among the abovementioned TBI parameters, high instantaneous dose rate seems to be the main risk factor of cataract formation, and the administration of heparin appears to have a protective role in cataractogenesis. On the other hand, ionizing radiation seems to have a protective effect on posterior capsule opacification following extracapsular cataract extraction and intraocular lens implantation.