A low-cost and versatile system for projecting wide-field visual stimuli within fMRI scanners.

We have constructed and tested a custom-made magnetic-imaging-compatible visual projection system designed to project on a very wide visual field (~80°). A standard projector was modified with a coupling lens, projecting images into the termination of an image fiber. The other termination of the fiber was placed in the 3-T scanner room with a projection lens, which projected the images relayed by the fiber onto a screen over the head coil, viewed by a participant wearing magnifying goggles. To validate the system, wide-field stimuli were presented in order to identify retinotopic visual areas. The results showed that this low-cost and versatile optical system may be a valuable tool to map visual areas in the brain that process peripheral receptive fields.

Inhibition of the immunoproteasome modulates innate immunity to ameliorate muscle pathology of dysferlin-deficient BlAJ mice.

Muscle repair in dysferlinopathies is defective. Although macrophage (Mø)-rich infiltrates are prominent in damaged skeletal muscles of patients with dysferlinopathy, the contribution of the immune system to the disease pathology remains to be fully explored. Numbers of both pro-inflammatory M1 Mø and effector T cells are increased in muscle of dysferlin-deficient BlAJ mice. In addition, symptomatic BlAJ mice have increased muscle production of immunoproteasome. In vitro analyses using bone marrow-derived Mø of BlAJ mice show that immunoproteasome inhibition results in C3aR1 and C5aR1 downregulation and upregulation of M2-associated signaling. Administration of immunoproteasome inhibitor ONX-0914 to BlAJ mice rescues muscle function by reducing muscle infiltrates and fibro-adipogenesis. These findings reveal an important role of immunoproteasome in the progression of muscular dystrophy in BlAJ mouse and suggest that inhibition of immunoproteasome may produce therapeutic benefit in dysferlinopathy.

CD20-related signaling pathway is differently activated in normal and dystrophic circulating CD133(+) stem cells.

Among the heterogeneous population of circulating hematopoietic and endothelial progenitors, we identified a subpopulation of CD133(+) cells displaying myogenic properties. Unexpectedly, we observed the expression of the B-cell marker CD20 in blood-derived CD133(+) stem cells. The CD20 antigen plays a role in the modulation of intracellular calcium homeostasis through signaling pathways activation. Several observations suggest that an increase in intracellular calcium concentration ([Ca(2+)](i)) could be involved in the etiology of the Duchenne muscular dystrophy (DMD). Here, we show that a CD20-related signaling pathway able to induce an increase in [Ca(2+)](i) is differently activated after brain derived neurotrophic factor (BDNF) stimulation of normal and dystrophic blood-derived CD133(+) stem cells, supporting the assumption of a "CD20-related calcium impairment" affecting dystrophic cells. Presented findings represent the starting point toward the expansion of knowledge on pathways involved in the pathology of DMD and in the behavior of dystrophic blood-derived CD133(+) stem cells.

CEA concentration and cytology in duodenal fluid collected during the Secretin-Pancreozymin test. Attempt at an early diagnosis of pancreatic carcinoma by means of simple procedure.

CEA concentration in juice collected during the Secretin-Pancreozymin test, and cytology were evaluated in order to establish whether they may be used as an aid in the diagnosis of pancreatic carcinoma before resorting to x-ray examinations. Thirty-three subjects were studied: 6 normal subjects, 12 with chronic pancreatitis, 3 after recovery from acute pancreatitis, 8 with gall-stones, 3 with carcinoma of the pancreas and 1 with cancer of the biliary tract. Three duodenal juice samples (at 30, 60 and 90 mins of hormonal infusion) were taken in each subject for CEA, cytology, bicarbonate and trypsin determinations. Although a significant statistical difference was noted between normal subjects and patients with carcinoma of the pancreas in the 30-min-juice sample, CEA concentration in the duodenal juice did not seem a reliable index in the diagnosis of pancreatic carcinoma. The information provided by cytology was also very scanty and sometimes misleading. The clinical picture and radiological investigation still remain the surest basis for the diagnosis of pancreatic cancer.

[Immunologic changes in chronic pancreatitis]. / Alterazioni immunologiche nella pancreatite cronica.

In 35 patients with chronic pancreatitis, C3, C4, s-immunoglobulins, circulating immunocomplexes and T-lymphocytes were assessed in order to verify whether an immunological role may be postulated in the pathogenesis and/or in the maintenance of the disease. A significant increase of serum IgM together with normal values of C3 and C4 and without circulating immunocomplexes was found. A significant decrease in the total number of lymphocytes as well as in the number and percentage of T-lymphocytes was also documented. These results suggest a possible involvement of immunological (humoral and cellular) processes in maintaining the chronic pancreatic damage.

T and B lymphocyte depletion has a marked effect on the fibrosis of dystrophic skeletal muscles in the scid/mdx mouse.

Abnormal connective tissue proliferation following muscle degeneration is a major pathological feature of Duchenne muscular dystrophy (DMD), a genetic myopathy due to lack of the sarcolemmal dystrophin protein. Since this fibrotic proliferation is likely to be a major obstacle to the efficacy of future therapies, research is needed to understand and prevent the fibrotic process in order to develop an effective treatment. Murine muscular dystrophy (mdx) is genetically homologous to DMD, and histopatological alterations are comparable to those of the muscles of patients with DMD. To investigate the development of fibrosis, we bred the mdx mouse with the scid immunodepressed mouse and analysed fibrosis histologically; we used ELISA analysis to determine TGF-beta1 expression. Significant reduction of fibrosis and TGF-beta1 expression was found in the muscles of the scid/mdx mice. However, we observed similar centrally located nuclei, necrosis, muscle degeneration and muscle force compared to the mdx animals. These data demonstrate a correlation between the absence of B and T lymphocytes and loss of fibrosis accompanied by reduction of TGF-beta1, suggesting the importance of modulation of the immune system in DMD.

Skin-derived stem cells transplanted into resorbable guides provide functional nerve regeneration after sciatic nerve resection.

The regeneration in the peripheral nervous system is often incomplete and the treatment of severe lesions with nerve tissue loss is primarily aimed at recreating nerve continuity. Guide tubes of various types, filled with Schwann cells, stem cells, or nerve growth factors are attractive as an alternative therapy to nerve grafts. In this study, we evaluated whether skin-derived stem cells (SDSCs) can improve peripheral nerve regeneration after transplantation into nerve guides. We compared peripheral nerve regeneration in adult rats with sciatic nerve gaps of 16 mm after autologous transplantation of GFP-labeled SDSCs into two different types of guides: a synthetic guide, obtained by dip coating with a L-lactide and trimethylene carbonate (PLA-TMC) copolymer and a collagen-based guide. The sciatic function index and the recovery rates of the compound muscle action potential were significantly higher in the animals that received SDSCs transplantation, in particular, into the collagen guide, compared to the control guides filled only with PBS. For these guides the morphological and immunohistochemical analysis demonstrated an increased number of myelinated axons expressing S100 and Neurofilament 70, suggesting the presence of regenerating nerve fibers along the gap. GFP positive cells were found around regenerating nerve fibers and few of them were positive for the expression of glial markers as S-100 and glial fibrillary acidic protein. RT-PCR analysis confirmed the expression of S100 and myelin basic protein in the animals treated with the collagen guide filled with SDSCs. These data support the hypothesis that SDSCs could represent a tool for future cell therapy applications in peripheral nerve regeneration.

Serum ferritin in pancreatic disease. An accurate test of malignancy?

Serum ferritin, described as increased in patients with pancreatic cancer, was studied in 109 subjects by an immunoradiometric technique in order to assess its reliability in detecting pancreatic malignancy. A significant increase of serum ferritin was found in pancreatic cancer as compared to controls (p less than 0.01), to calcifying (p less than 0.05), non-calcifying (p less than 0.05), and recurrent (p less than 0.01) chronic pancreatitis. Nevertheless, high levels of serum ferritin were found in 10 out of the 36 chronic pancreatitis patients and in 10 out of the 26 patients with non-pancreatic diseases, whilst values within the normal range were detected in 6 out of the 22 pancreatic cancer patients. These data suggest that serum ferritin, although frequently increased in pancreatic cancer, cannot be considered a marker of pancreatic malignancy.