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Combined therapy of silymarin and desferrioxamine in patients with ,-thalassemia major: a randomized double-blind clinical trial

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2009
Marjan Gharagozloo
Abstract Silymarin, a flavonolignan complex isolated from Silybum marianum, has a strong antioxidant, hepatoprotective, and iron chelating activities. The present study was designed to investigate the therapeutic activity of orally administered silymarin in patients with thalassemia major under conventional iron chelation therapy. A 3-month randomized, double-blind, clinical trial was conducted in 59 ,-thalassemia major patients in two well-matched groups. Patients were randomized to receive a silymarin tablet (140 mg) three times a day plus conventional desferrioxamine therapy. The second group received the same therapy but a placebo tablet instead of silymarin. Clinical laboratory tests were assessed at the beginning and the end of the trial, except for serum ferritin level that was assessed at the middle of the trial as well. Results of this study revealed that the combined therapy was well tolerated and more effective than desferrioxamine in reducing serum ferritin level. Significant improvement in liver alkaline phosphatase and glutathione levels of red blood cells was also observed in silymarin-treated ,-thalassemia patients. However, no significant difference in serum ferritin levels was detected between silymarin and placebo groups after 1.5 and 3 months treatment, probably because of insufficient sample size to detect subtle changes in ferritin levels between groups. This is the first report showing the beneficial effects of silymarin in thalassemia patients and suggests that silymarin in combination with desferrioxamine can be safely and effectively used in the treatment of iron-loaded patients. [source]


Novel neuroprotective, neuritogenic and anti-amyloidogenic properties of 2,4-dinitrophenol: The gentle face of Janus

IUBMB LIFE, Issue 4 2006
Fernanda G. De Felice
Abstract In Roman mythology, Janus was the god of gates, doors, beginnings and endings. He was usually depicted with two faces looking in opposite directions. Janus was frequently used to symbolize change and transitions, such as the progression from past to future or from one viewpoint to another. 2,4-dinitrophenol (DNP) and other nitrophenols have long been known to be toxic at high concentrations (the 'bad' face of DNP), an effect that appears essentially related to interference with cellular energy metabolism due to uncoupling of mitochondrial oxidative phosphorylation. Five years ago, however, we published the first report showing that low concentrations of DNP protect neurons against the toxicity of the amyloid-, peptide (De Felice et al. (2001) FASEB J. 15:1297 - 1299]. Since then, other studies have provided evidence of beneficial actions of DNP (at low concentrations), including neuroprotection against different types of insult, blockade of amyloid aggregation, stimulation of neurite outgrowth and neuronal differentiation, and even extension of lifespan in certain organisms. Some of these effects appear to be due to mild mitochondrial uncoupling and prevention of cellular oxidative stress, whereas other actions are related to activation of additional intracellular signaling pathways. Thus, a novel and 'gentle' face of DNP is emerging from such studies. In this review, we discuss both toxic and beneficial actions of DNP. The evidence available so far suggests that DNP and other compounds with similar biological activities may be of significant interest to the development of novel therapeutic approaches for neurodegenerative diseases and other neurological disorders. iubmb Life, 58: 185-191, 2006 [source]


Infectious gastroenteritis caused by Vibrio harveyi (V. carchariae) in cultured red drum, Sciaenops ocellatus

JOURNAL OF APPLIED ICHTHYOLOGY, Issue 1 2003
P.-C. Liu
Summary An outbreak of serious mortality among the cultured red drum Sciaenops ocellatus (L.) characterized by a swollen intestine containing transparent yellow fluid (ascites and gastroenteritis) occurred in July 2000 in Taiwan. A motile strain Rd 0700 was isolated from head kidney and/or the intestinal yellow fluid on tryptone soya agar (TSA) supplemented with 2% (w/v) NaCl and/or thiosulfate citrate bile salt (TCBS) sucrose agar plates. Applying biochemical characteristics, this strain was characterized and identified as Vibrio harveyi (V. carchariae). The bacteria could be re-isolated from kidney, liver, and the transparent yellow fluid of swollen intestine of fish after bacterial challenge. The LD50 values of the organism and its extracellular products (ECP) were 2.9×107 colony forming units (CFU) and 3.85 ,g protein g,1 fish body weight, respectively. All moribund/dead fish exhibited gastroenteritis except those killed within 12 h. This is a first report showing that intraperitoneal (i.p.) injection of the ECP from V. carchariae is lethal to red drum and can reproduce gastroenteritis in the fish. [source]


Tyrosine-phosphorylated STAT5 accumulates on podosomes in Hck-transformed fibroblasts and chronic myeloid leukemia cells

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2007
Renaud Poincloux
In chronic myeloid leukemia (CML), the transforming activity of Bcr/Abl involves constitutive activation of the phagocyte specific Src-family tyrosine kinase Hck, which in turn directly activates the signal transducer and activator of transcription 5 (STAT5). The effect of Hck on STAT5 was first explored independently of Bcr/Abl by expressing the constitutively active Hck mutant (Hckca) in MEF3T3-TetOff fibroblasts. As previously reported, Hckca -expressing cells form podosomes which are actin-rich structures involved in trans-tissular cell migration and found in the few cell types able to cross anatomic boundaries. We demonstrated that in these cells, the tyrosine-phosphorylated form of STAT5 (PY-STAT5) increased and preferentially localized on podosomes together with Hck, instead of translocating to the nucleus as observed with conventional stimuli such as IFN,. To examine whether similar results were obtained in the presence of Bcr/Abl, the CML cell line K562 was used. We observed that (i) podosomal structures are present in these cells in contrast to Bcr/Abl-negative leukemic cells, (ii) podosome formation was inhibited by Bcr/Abl- and Src-kinase inhibitors, and (iii) PY-STAT5 mainly colocalized with Hck on these structures. The presence of podosomes was not sufficient to trap STAT5 since in normal macrophages which spontaneously form podosomes and express regulated Hck, PY-STAT5 is in the nucleus. In conclusion, this is the first report showing that PY-STAT5 associates to podosomes in a process dependent on constitutive activation of Hck. We propose that STAT5, previously classified as a transcription factor, could play another role outside the nucleus, elicited by the Bcr/Abl-Hck transforming pathway. J. Cell. Physiol. 213: 212,220, 2007. © 2007 Wiley-Liss, Inc. [source]


Edwardsiella tarda infection in Korean catfish, Silurus asotus, in a Korean fish farm

AQUACULTURE RESEARCH, Issue 1 2009
Jin-Ha Yu
Abstract Mass mortality of Korean catfish, Silurus asotus, occurred in a culture farm situated in Jeollabukdo Province, Korea. The cumulative mortality rates reached up to 5% of the total fish in the farm per day. In clinical signs, the affected fish showed abdominal distension, vent protrusion, enteritis, liver congestion and abscess-like lesions in enlarged spleen and kidney. Histopathologically, in the liver, hepatocytes lost fat and underwent atrophy or necrosis. The spleen showed necrotized splenocytes and a haemorrhagic pulp. In the kidney, glomerular destruction, degeneration of renal tubular epithelial cell and haemorrhage were observed. However, necrotic muscular lesions were not observed. A pure bacterial isolate was obtained from the liver, spleen and kidney lesions of affected fish. Experimental infection of normal catfish with the isolate resulted in the development of clinical signs similar to those seen on the farm. The isolates were identified as Edwardsiella tarda through biochemical tests (99.4%) and analysis of bacterial genes (16S rDNA) sequences (98%). The bacteria possessed two virulent genes: sodB and katB genes. These results suggest that E. tarda can act as a pathogen of farmed catfish. This is the first report showing that E. tarda caused mortality in cultured Korean catfish. [source]


Isolation of an anti-angiogenic substance from Agaricus blazei Murill: Its antitumor and antimetastatic actions

CANCER SCIENCE, Issue 9 2004
Yoshiyuki Kimura
We previously found that ergosterol isolated from Agaricus blazei inhibited tumor growth through the inhibition of tumor-induced neovascularization. In the present study, we isolated further anti-angiogenic substances (A-1 and A-2) from this fungus using an assay system of angiogenesis induced by Matrigel supplemented with vascular endothelial growth factor, and A-1 was identified as sodium pyroglutamate. Next, we examined the antitumor and antimetastatic actions of A-1 using Lewis lung carcinoma (LLC)-bearing mice. A-1 (30, 100 and 300 mg/kg) inhibited tumor growth and metastasis to the lung. The reduction of the numbers of splenic lymphocytes, CD4+ and CD8+ T cells in LLC-bearing mice was inhibited by the oral administration of A-1 (30, 100 and 300 mg/kg). Further, A-1 increased the number of apoptotic cells of tumors and the numbers of CD8+ T and natural killer cells invading the tumors, and inhibited the increase of von Willebrand factor expression (a measure of angiogenesis) in the tumors. These results suggest that the antitumor and antimetastatic actions of A-1 (sodium pyroglutamate) may be associated with inhibition of the reduction of immune response caused by the tumor growth and tumor-induced neovascularization. This is the first report showing that sodium pyroglutamate isolated from A. blazei as an anti-angiogenic substance has potent antitumor and antimetastatic actions, as well as immune-modulatory activity, in tumor-bearing mice. [source]