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University of Florence scientists detail new medical studies and findings(Science Letter Via Thomson Dialog NewsEdge) University of Florence scientists detail new medical studies and findings. This trend article about University of Florence is an immediate alert from NewsRx to identify developing directions of research. Study 1: The marine product aplidine (APL) combats overexpressed VEGF (vascular endothelial growth factor) in leukemia cells. "APL is a marine depsipeptide isolated from the Mediterranean tunicate Aplidium albicans that is under clinical phase II development. In contrast to the lack of bone marrow toxicity reported in phase I/II studies, it has been shown to induce cytotoxicity at very low concentration against lymphoblastic leukemia blast, as well as having an impact in the VEGF/VEGF receptor 1 loop," scientists in Italy report. "To confirm these findings we investigated APL-related VEGF inhibition and its cytotoxic effect on myeloid leukemic cells lines (K-562, HEL and HL60) and fresh leukemia blasts derived from 30 patients with acute myeloid leukemia (AML). The conventional active 4-demetoxidaunorubicin (idarubicin; IDA) was included as a positive control," described M. Biscardi and colleagues, University of Florence. According to investigators, "APL was found to be significantly (p<.001) more active than IDA in obtaining 50% growth-inhibition in K-562, HEL and HL60 cell lines. Results obtained with AML blast cells were superimposible. ID50 ranged from 0.024 to 0.610 mcM for IDA (0.2000.176) and from 0.001 to 0.108 mcM for APL (0.0200.031). Annexin V tests and cell cycle analysis performed on cell lines confirmed the stronger cytotoxic capability of APL as apoptotic inducer and as a G1 blocker." "The inhibitory effects of APL on VEGF release and secretion have been confirmed by ELISA tests performed on HEL: the VEGF concentration in cell surnatant was reduced from 169 to 36 pg/ml after 24 h of exposure to a pharmacological concentration of APL." "APL harbors a strong in vitro antileukemic activity at a concentration achievable in patients at non-myelotoxic doses. Our data also support the notion of an impact on VEGF secretion. Clinical studies with this new marine-derived compound in relapsed/resistant leukemia are underway," researchers indicated. Biscardi and colleagues published their study in Annals of Oncology (VEGF inhibition and cytotoxic effect of aplidin in leukemia cell lines and cells from acute myeloid leukemia. Ann Oncol, 2005;16(10):1667-1674). For more information, contact A. Grossi, Istituto Leonardo da Vinci, Via Colletta 22-R, I-50100 Firenze, Italy. Study 2: Markers of hypercoagulability and inflammation predict mortality in patients with heart failure. Researchers working in Italy report, "Plasma levels of inflammatory markers are increased in chronic heart failure (HF) and are also subclinical indicators of future HF. Inflammation is strictly correlated with clotting activation, but the association between inflammation, hypercoagulability and prognosis in HF has not been previously reported." University of Florence scientists R. Marcucci and colleagues explained, "Markers of inflammation (interleukin-6, IL-6; and C-reactive protein, CRP) and hypercoagulability (D-dimer, DD; and thrombin-antithrombin III complex, TAT) were prospectively assessed in 214 subjects with New York Heart Association (NYHA) functional class II-IV HF. During a median follow-up of 8.5 months, 32 patients had an event: 13 died and 19 were hospitalized because of worsening of HF." They continued, "IL-6, DD and TAT levels were all significantly associated with increased risk of death after adjustment for other known HF prognostic factors (age, gender, traditional cardiovascular risk factors, NYHA class, systolic left ventricular function, renal failure, hemoglobin, serum sodium) in a Cox multivariate proportional hazard model (p=0.003, p=0.01 and p=0.02, respectively)." "When these markers were added simultaneously to the known prognostic factors in a new Cox multivariate model," the investigators added, "only DD levels were significant predictors of mortality (hazard ratio [95% confidence interval; CI]: 11 [2.7-45.1], p=0.001). The Kaplan-Meier curve revealed a significantly better outcome in patients with DD below 450 ng mL-1. NT-pro-BNP was the only significant predictor of rehospitalization (HR [95% CI]: 5.3 [2.0-13.8], p<0.001)." "Hypercoagulability and inflammation, as assessed by DD, TAT and IL-6 levels, are associated with an increased mortality risk in HF," concluded the authors. Marcucci and colleagues published their study in the Journal of Thrombosis and Haemostasis (Markers of hypercoagulability and inflammation predict mortality in patients with heart failure. J Thromb Haemost, 2006;4(5):1017-1022). For additional information, contact R. Marcucci, University of Florence, Dept. of Heart & Vessels, Azienda Ospedale, University of Careggi, Viale Morgagni 85, I-50134 Florence, Italy. Study 3: According to recent research from Italy published in the journal Arthritis and Rheumatism, neuronal nitric oxide synthase varies in systemic sclerosis (SSc) skin. "In SSc, derangement of the peripheral nervous system is linked to vascular tone dysfunction. Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS, NOS-I) might play a dynamic role in the control of vascular tone." "This study was performed to verify, by immunohistochemical and biochemical analyses, the presence and expression of nNOS and protein gene product 9.5 (PGP 9.5) in SSc skin, in different subsets and various phases of the disease," wrote L. Ibbamanneschi and colleagues, University of Florence. "Biopsy samples of clinically involved skin from 32 SSc patients (12 with limited cutaneous SSc [IcSSc] and 20 with the diffuse form [dcSSc]) and skin samples from 6 healthy controls were either immunostained with anti-PGP 9.5 and anti-nNOS antibodies or analyzed by semiquantitative reverse transcription-polymerase chain reaction and Western blotting." The authors observed, "Immunohistochemical and biochemical data showed a decrease in PGP 9.5 and nNOS innervation and in their messenger RNA (mRNA) levels in IcSSc and dcSSc skin. In the edematous phase of SSc, a light alteration in cutaneous innervation was initiated and slowly progressed into the sclerotic phase, becoming most evident in the atrophic phase." "Levels of nNOS mRNA were significantly lower between the edematous phase and the sclerotic phase in both dcSSc and IcSSc skin, which was attributable to the earlier occurrence of more severe pathologic alterations." "Total cutaneous innervation and nNOS innervation slowly disappear in the skin of SSc patients. Expression of nNOS depends on the severity of tissue damage in SSc, and increased synthesis of NO also contributes to this process," the scientists continued. They concluded, "It remains to be determined whether the changes in cutaneous innervation are due to the disease itself or whether these changes contribute to the pathogenesis and evolution of SSc." Ibbamanneschi and colleagues published their study in Arthritis and Rheumatism (Variations of neuronal nitric oxide synthase in systemic sclerosis skin. Arthritis Rheum, 2006;54(1):202-213). For additional information, contact L. Ibbamanneschi, University of Florence, Department of Anatomy, Histolofy & Forensic Medicine, Viale GB Morgagni 85, I-50134 Florence, Italy. The publisher's contact information for the journal Arthritis and Rheumatism is: Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA. This article was prepared by Science Letter editors from staff and other reports. Copyright 2007, Science Letter via NewsRx.com. Copyright 2007 Science Letter via NewsRx.com |