Search results for "COMPOUND"
showing 10 items of 35174 documents
Ovarian and Adrenal Hyperandrogenism
2007
Because in normal women androgens are secreted in almost equal quantities by both adrenals and ovaries, for many years many studies have tried to distinguish the source of androgen excess. However, in the last 10-15 years, the diagnoses of ovarian or adrenal hyperandrogenism have almost disappeared. This is due to the lack of specificity of dynamic tests as well as to the emphasis given on clinical information and ovarian sonography for the diagnosis of hyperandrogenic syndromes. However, determination of the source of increased androgens may still be useful for improving the classification and the understanding of androgen excess disorders. The aim of this review is to examine the source o…
Activation of mGlu3 Receptors Stimulates the Production of GDNF in Striatal Neurons
2009
Metabotropic glutamate (mGlu) receptors have been considered potential targets for the therapy of experimental parkinsonism. One hypothetical advantage associated with the use of mGlu receptor ligands is the lack of the adverse effects typically induced by ionotropic glutamate receptor antagonists, such as sedation, ataxia, and severe learning impairment. Low doses of the mGlu2/3 metabotropic glutamate receptor agonist, LY379268 (0.25-3 mg/kg, i.p.) increased glial cell line-derived neurotrophic factor (GDNF) mRNA and protein levels in the mouse brain, as assessed by in situ hybridization, real-time PCR, immunoblotting, and immunohistochemistry. This increase was prominent in the striatum, …
FLT3 as a therapeutic target in AML: still challenging after all these years
2010
Abstract Mutations within the FMS-like tyrosine kinase 3 (FLT3) gene on chromosome 13q12 have been detected in up to 35% of acute myeloid leukemia (AML) patients and represent one of the most frequently identified genetic alterations in AML. Over the last years, FLT3 has emerged as a promising molecular target in therapy of AML. Here, we review results of clinical trials and of correlative laboratory studies using small molecule FLT3 tyrosine kinase inhibitors (TKIs) in AML patients. We also review mechanisms of primary and secondary drug resistance to FLT3-TKI, and from the data currently available we summarize lessons learned from FLT3-TKI monotherapy. Finally, for using FLT3 as a molecul…
Cigarette smoke-induced pulmonary endothelial dysfunction is partially suppressed by sildenafil.
2009
Abstract Cigarette smoke mediated oxidative stress and endothelial dysfunction are important processes in the pathogenesis of several lung disorders. In this study we evaluated the effect of PDE5 inhibition on pulmonary artery endothelial dysfunction induced by cigarette smoke in vitro . Human pulmonary artery endothelial cells (HPAEC) were incubated in the absence or presence of PDE5 inhibitor sildenafil (10 nM–1 μM), PKG agonist 8-Br-cGMP (1 mM), or the antioxidants dyphenyleneiodonium (DPI 1 μM) and N -acetylcysteine (NAC 1 mM) for 30 min. Then, cigarette smoke extract (CSE) was added for 24 h. CSE (2.5–10%)-induced ROS generation was suppressed by DPI, and partially reversed by sildenaf…
Role of insulin-like growth factors in autocrine growth of human retinoblastoma Y79 cells.
1996
In this study, we have demonstrated that human retinoblastoma Y79 cells produce insulin-like growth factors (IGFs) type I and type II and release them into the medium. We have also ascertained, by means of competitive studies and cross-linking procedure, that Y79 cells contain the type-I IGF receptor (IGF-IR). Furthermore, surface-bound IGF-I is internalised by the receptor, then degraded to amino acids. Insulin, IGF-I and IGF-II caused down-regulation of IGF-IR; the effect is concentration and time dependant. Scatchard analysis demonstrated that incubation with insulin markedly decreased the binding capacity measured for IGF-I while the apparent Kd value calculated for IGF-I binding was no…
Induction of dendritic cell maturation and modulation of dendritic cell-induced immune responses by prostaglandins
2000
Dendritic cells (DC) are the most potent antigen-presenting cells of the immune system. In this study we investigated the effects of various prostaglandins (PG) on the stimulatory capacity of DC. DC were generated from peripheral progenitor cells in the presence of IL-4 and GM-CSF and stimulated with IL-1, IL-6 and TNF-alpha on day 7. Simultaneously, PG (PGD(2), PGE(1), PGE(2), PGF(2 alpha), PGI(2)) were added at various concentrations (10(-5) to 10(-9) M) on day 7. In all experiments, PGE(2) had the most potent influence on the maturation of the DC, followed by other PG in the order PGE(1) > PGD(2) > PGF(2 alpha) > PGI(2). In addition, the expression of the surface molecules CD40, CD54, CD…
One or two ligatures inducing periodontitis are sufficient to cause fatty liver
2017
Background Periodontitis is a chronic disease that due to an intense inflammatory response triggers systemic changes such as hepatic alterations. This study aimed to compare hepatic damage in rats that received experimental periodontitis at one or two periodontal sites with ligatures. Material and Methods Eighteen rats were separated into three groups: control, without ligature; periodontitis 1, with one ligature; and periodontitis 2, with two ligatures. The following parameters were assessed: gingival bleeding index, probing pocket depth, tooth mobility, alveolar bone loss, malondialdehyde (MDA) and myeloperoxidase (MPO) activity in periodontal tissue; histopathological evaluation of hepat…
Hepatitis C virus infection in hemodialyzed patients.
2007
In spite of our present improved knowledge of the epidemiology and pathways of contamination of the hepatitis C virus (HCV), infection still remains a public health problem. One category of patients who have suffered greatly from the consequences of HCV infection is certainly that of hemodialysis patients. In the past, in fact, their need for transfusions exposed these patients to infection and, as a result, subjects on dialysis for over 15 years are today paying the price for those inevitable transfusions, as the virus and its pathways of contagion were unknown then. However, still today, albeit at a much lower prevalence, even subjects with a shorter dialysis age present a higher prevalen…
Thrombopoietin Receptor Agonists for Severe Thrombocytopenia after Allogeneic Stem Cell Transplantation: Experience of a Multicenter Study from the G…
2018
Abstract Introduction Thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Underlying mechanisms are poorly known and usually multifactorial. Its treatment is not well defined, mostly based in platelet transfusion. Thus, is important to identify new strategies to manage this important post-SCT complication. Romiplostim and Eltrombopag are currently available thrombopoietin receptor agonists (TPO-RAs) that stimulate platelet production. Some studies with very small number of cases have reported their potential efficacy in the allo-SCT setting. For this reason, the aim of our study is to analyze the efficacy and safety of TPO-RAs for s…
Albumin versus solvent/detergent-treated pooled plasma as replacement fluid for long-term plasma exchange therapy in a patient with primary hypertrig…
2015
BACKGROUND Chylomicronemia syndrome is a metabolic condition characterized by severe fasting hypertrigliceridemia (≥1000 mg/dL) and other clinical features including chronic abdominal pain and recurrent acute pancreatitis. In patients with acute or recurrent pancreatitis, plasma exchange (PEx) is indicated for the treatment of acute disease and prevention of recurrence. The use of plasma instead of albumin as replacement fluid has been suggested for its putative ability to replace the deficient enzyme possibly leading to better clinical improvement. CASE REPORT A 40-year-old man with chylomicronemia syndrome due to a newly identified loss-of-function mutation in the lipoprotein lipase (LPL)…