45 research outputs found
Glatiramer Acetate-associated Refractory Immune Thrombocytopenic Purpura
We present a case of glatiramer acetate-associated refractory immune thrombocytopenic purpura (ITP) in a female patient with multiple sclerosis. A search of MEDLINE/PubMed did not find any connection between glatiramer acetate and thrombocytopenia, specifically ITP. The autoimmune reaction was resistant to conservative ITP treatment, and was eventually managed only by splenectomy. To the best of our knowledge, this is the first report of glatiramer acetate-associated ITP. Physicians should be aware of this condition, and consider performing routine blood counts at the beginning of glatiramer acetate treatment
Stimulation of the Sphenopalatine Ganglion Induces Reperfusion and Blood-Brain Barrier Protection in the Photothrombotic Stroke Model
The treatment of stroke remains a challenge. Animal studies showing that electrical stimulation of the sphenopalatine ganglion (SPG) exerts beneficial effects in the treatment of stroke have led to the initiation of clinical studies. However, the detailed effects of SPG stimulation on the injured brain are not known.The effect of acute SPG stimulation was studied by direct vascular imaging, fluorescent angiography and laser Doppler flowmetry in the sensory motor cortex of the anaesthetized rat. Focal cerebral ischemia was induced by the rose bengal (RB) photothrombosis method. In chronic experiments, SPG stimulation, starting 15 min or 24 h after photothrombosis, was given for 3 h per day on four consecutive days. Structural damage was assessed using histological and immunohistochemical methods. Cortical functions were assessed by quantitative analysis of epidural electro-corticographic (ECoG) activity continuously recorded in behaving animals.Stimulation induced intensity- and duration-dependent vasodilation and increased cerebral blood flow in both healthy and photothrombotic brains. In SPG-stimulated rats both blood brain-barrier (BBB) opening, pathological brain activity and lesion volume were attenuated compared to untreated stroke animals, with no apparent difference in the glial response surrounding the necrotic lesion.SPG-stimulation in rats induces vasodilation of cortical arterioles, partial reperfusion of the ischemic lesion, and normalization of brain functions with reduced BBB dysfunction and stroke volume. These findings support the potential therapeutic effect of SPG stimulation in focal cerebral ischemia even when applied 24 h after stroke onset and thus may extend the therapeutic window of currently administered stroke medications
Transformation of Low-Grade Follicular Yymphoma with Partial Marginal Zone Differentiation: Two Cases
Two cases of low-grade follicular lymphoma, with marginal zone differentiation and/or with high proliferation rate in one of them, are reported with transformation into high grade B-cell and B-lymphoblastic lymphomas. The contribution of these features to the transforming process, although previously described, is infrequent, and has not been deciphered to date
Cell death induction of chronic lymphocytic leukemia lymphocytes using VDAC1-based peptides: A novel therapeutic approach
Inhibition of muscle fibrosis and improvement of muscle histopathology in dysferlin knock-out mice treated with halofuginone
Absence of, or loss-of-function mutations in
the dysferlin gene (dysf) result in dysferlinopathy,
characterized by increased muscle inflammation,
collagen deposition and deterioration in muscle function.
We evaluated halofuginone efficacy in improving
muscle histopathology in mice with deleted dysf
transmembrane domain. Quadriceps sublumbar and
longissimus muscles of 9-month-old dysf-/- mice treated
with halofuginone for 4 months exhibited a reduction in
centrally-nucleated myofibers, inflammatory infiltrates
and collagen content. Late onset of dysferlinopathy
makes it ideal for evaluating the efficacy of early
treatments on late outcome. The dysf-/- mice were
treated with halofuginone for 3 to 4 months starting at 1,
5 or 9 months of age, and quadricep muscle
histopathology was evaluated at 12 months. Collagen
content and number of centrally nucleated myofibers
decreased after early halofuginone treatment,
administered when myofibers with central nuclei and
inflammatory infiltrates are evident, but there was
almost no fibrosis. When administered at the beginning
of fibrosis it resulted in a further decrease in the number
of centrally-nucleated myofibers with no additional
decrease in collagen levels. Cardiac fibrosis was almost
completely abolished following early halofuginone
treatment. Halofuginone inhibited Smad3
phosphorylation and its translocation to the nucleus and
increased the activity of matrix metalloproteinases 9 and
2 responsible for resolution of pre-existing collagen.
Macrophage and myofibroblast invasion into the
dystrophic muscle at the site of myofibers with central
nuclei was inhibited by halofuginone. These results
suggest that early halofuginone treatment can prevent
the late outcome of dysferlinopathy and can cause
resolution of the established fibrosis when administered
at later stages
Elevated growth differentiation factor 15 expression in patients with congenital dyserythropoietic anemia type I
Congenital dyserythropoietic anemia (CDA) is a rare group of red blood cell disorders characterized by ineffective erythropoiesis and increased iron absorption. To determine whether growth differentation factor 15 (GDF15) hyper-expression is associated with the ineffective erythropoiesis and iron-loading complications of CDA type I (CDA I), GDF15 levels and other markers of erythropoiesis and iron overload were studied in blood from 17 CDA I patients. Significantly higher levels of GDF15 were detected among the CDA I patients (10 239 ± 3049 pg/mL) compared with healthy volunteers (269 ± 238 pg/mL). In addition, GDF15 correlated significantly with several erythropoietic and iron parameters including Hepcidin-25, Ferritin, and Hepcidin-25/Ferritin ratios. These novel results suggest that CDA I patients express very high levels of serum GDF15, and that GDF15 contributes to the inappropriate suppression of hepcidin with subsequent secondary hemochromatosis