Antoine Buemi

Università degli Studi di Messina, Messina, Sicily, Italy

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Publications (27)77.28 Total impact

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    ABSTRACT: Man is water. When life appeared on earth, the primordial cell had a simple structure and could immediately ascertain from the surrounding aquatic environment the substances for nutrition and oxygen, without any need for structural complexity. As part of evolution, during the transition from aquatic to terrestrial life, vertebrates had to fight against dehydration as well as fish in the sea. In this complex mechanism of osmoregulation, the structure and function of some osmoregulatory hormones have been maintained during the evolution of species, from fish to man. Within the homeostatic mechanism, the renin-angiotensin-aldosterone system (RAAS) is crucial in the regulation of renal reasorption of water and sodium. It is also involved in the regulation of renal plasma flux, blood volume and blood pressure. Vasopressin plays a hormonal function in the mechanisms of water homeostasis acting through Aquaporins (AQP), channel-proteins that allow bi-directional water transport across cell membranes. © 2014 S. Karger AG, Basel.
    05/2014; 33(5):1369-1388.
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    ABSTRACT: Apelin regulates angiogenesis, stimulating endothelial cell proliferation and migration. It is upregulated during tumor angiogenesis, and its overexpression was reported to increase tumor growth. Furthermore, apelin controls vasopressin release and body fluid homeostasis. The aim of this study was to examine the correlations between apelin expression and clinical outcomes in oncologic patients, such as cancer disease progression and patient's survival. Apelin levels were evaluated in a cohort of 95 patients affected by different varieties of cancer. Partial remission and stable disease were assigned to the 'no progression' group, comparing it with the progressor group. Patients were followed up for 2 years. Receiver operating characteristics analysis was employed for identifying the progression of the oncologic disease and Kaplan-Meier curves assessed the survival. Adjusted risk estimates for progression endpoint were calculated using Cox proportional hazard regression analysis. Oncologic patients had higher apelin levels compared with healthy subjects, and apelin was closely related to the stages of the disease. In the hyponatremia group, apelin values were significantly higher than patients with eunatremia. After the follow-up of 24 months, 41 patients (43 %) reached the endpoint. Progressor subjects presented significantly increased apelin values at baseline compared with non-progressor. Univariate followed by multivariate Cox proportional hazard regression analysis showed that apelin predicted cancer progression independently of other potential confounders. In patients with cancer, apelin closely reflects the stage of the disease and represents a strong and independent risk marker for cancer progression.
    Clinical and Experimental Medicine 01/2014; · 2.83 Impact Factor
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    ABSTRACT: The synthesis of recombinant human erythropoietin has marked a turning point in the treatment of anaemia secondary to chronic kidney disease. However, the potentially fatal cardio- and cerebrovascular complications of the intake of high-doses of ESAs (erythropoiesis-stimulating agents), such as those observed in athletes who resort to doping, reason out the ever-prevalent debate concerning the balance between the risks and benefits of ESA administration for therapeutic purposes. Hence, there is still a discussion as to what values haemoglobin should ideally be maintained at. Additional concerns arise in cancer patients due to the ability of erythropoietin to act as an angiogenic and, in general, as a cell growth factor, because this might favour the progression of neoplastic disease. We summarized the prominent points of the latest guidelines on the management of anaemia in nephropathic patients, also identifying the possible risks that may result from the tendency to aim at too low haemoglobin levels.
    Current Medicinal Chemistry 09/2013; · 3.72 Impact Factor
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    ABSTRACT: Vasopressin (AVP) plays a detrimental role in autosomal dominant polycystic kidney disease (ADPKD). Copeptin represents a measurable substitute for circulating AVP whereas apelin counteracts AVP signaling. The aim of this study was to investigate the predictive value of apelin and copeptin for the progression of ADPKD disease. 52 ADPKD patients were enrolled and followed until the end of the observation period or the primary study endpoint was reached, defined by the combined outcome of decrease of glomerular filtration rate associated with a total renal volume increase. Receiver operating characteristics (ROC) analysis was employed for identifying the progression of renal disease and Kaplan-Meier curves assessed the renal survival. Adjusted risk estimates for progression endpoint and incident renal replacement therapy (RRT) were calculated using Cox proportional hazard regression analysis. ADPKD patients were characterized by lower apelin levels and higher copeptin levels when compared with healthy subjects. These biomarkers were strictly correlated with osmolality and markers of renal function. At ROC analysis, apelin and copeptin showed a very good diagnostic profile in identifying ADPKD progression. After the follow up of 24 months, 33 patients reached the endpoint. Cox proportional hazard regression analysis showed that apelin predicted renal disease progression and incident RRT independently of other potential confounders. Apelin is associated with kidney function decline in ADPKD, suggesting that it may be a new marker to predict kidney outcome.
    Peptides 08/2013; · 2.52 Impact Factor
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    ABSTRACT: The aim of this study was to demonstrate that neutrophil gelatinase-associated lipocalin (NGAL) increased before the onset of microalbuminuria in patients with type 1 diabetes mellitus (T1DM), representing an important biochemical parameter with high sensitivity and specificity to make a precocious diagnosis of "normoalbuminuric" diabetic nephropathy (DN). Serum NGAL (sNGAL) and urinary NGAL (uNGAL) levels were evaluated in a cohort of fifty patients affected by T1DM. They had no signs of clinical nephropathy. Thirty-five healthy subjects (HS) were recruited. sNGAL levels were significantly higher compared with those measured in HS [193.7 (103.2-405.4) vs. 46.4 (39.8-56.2) ng/ml; p < 0.0001], as were uNGAL levels [25.5 (14.2-40.2) vs. 6.5 (2.9-8.5) ng/ml; p < 0.0001]. sNGAL was found to be directly correlated with glycated hemoglobin. uNGAL also positively correlated with albuminuria, whereas an inverse correlation was found with uric acid. After multivariate analysis, significance was maintained for the correlation between uNGAL and microalbuminuria. In ROC analysis, sNGAL showed a good diagnostic profile such as uNGAL. NGAL increases in patients with T1DM, even before diagnosis of microalbuminuria representing an early biomarker of "normoalbuminuric" DN with a good sensitivity and specificity. NGAL measurement could be useful for the evaluation of early renal involvement in the course of diabetes.
    Acta Diabetologica 06/2013; · 4.63 Impact Factor
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    ABSTRACT: Background: Ultrafiltration failure and peritonitis are the most important limitations of peritoneal dialysis (PD). The aim of our study was to evaluate peritoneum damage through neutrophil gelatinase-associated lipocalin (NGAL), white blood cell (WBC) count and cancer antigen 125 (CA125). Patients and methods: Thirty patients with peritonitis and 30 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) were studied for 12 months. In the peritonitis group, blood samples and peritoneal fluid (lp) were collected before the onset of peritonitis, at the onset of peritonitis (T1) and every day until its resolution. CAPD patients were divided into 3 groups according to the treatment received. Long-dwell effluents were collected for NGAL, WBC count and Ca125 assessment. Results: In the peritonitis group, at time T1, NGAL levels were higher compared with baseline values. lpNGAL levels decreased at least 24 hours earlier than peritoneal WBC (lpWBC). At ROC analysis, lpNGAL was characterized by a very good diagnostic profile identifying treatment failure. In CAPD patients, the highest NGAL values were observed in the icodextrin group. An inverse correlation between lpNGAL, pKt/V and peritoneal ultrafiltration volume was also found. Conclusion: Mesothelial cells have an active role in the structural and functional alteration of the peritoneum during PD, and NGAL represents a valid biomarker for peritoneum evaluation.
    Journal of nephrology 05/2013; · 2.02 Impact Factor
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    ABSTRACT: Human relaxin-2 (hereafter simply defined as "relaxin") is a 6-kDa peptidic hormone best known for the physiological role played during pregnancy in the growth and differentiation of the reproductive tract and in the renal and systemic hemodynamic changes. This factor can also be involved in the pathophysiology of arterial hypertension and heart failure, in the molecular pathways of fibrosis and cancer, and in angiogenesis and bone remodeling. It belongs to the relaxin peptide family, whose members comprehensively exert numerous effects through interaction with different types of receptors, classified as relaxin family peptide (RXFP) receptors (RXFP1, RXFP2, RXFP3, RXFP4). Research looks toward the in-depth examination and complete understanding of relaxin in its various pleiotropic actions. The intent is to evaluate the likelihood of employing this substance for therapeutic purposes, for instance in diseases where a deficit could be part of the underlying pathophysiological mechanisms, also avoiding any adverse effect. Relaxin is already being considered as a promising drug, especially in acute heart failure. A careful study of the different RXFPs and their receptors and the comprehension of all biological activities of these hormones will probably provide new drugs with a potential wide range of therapeutic applications in the near future.
    Medicinal Research Reviews 02/2013; · 9.58 Impact Factor
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    ABSTRACT: Background: Acute kidney injury (AKI) develops in 10% of patients after surgical abdominal aortic aneurysm (AAA) repair. Neutrophil gelatinase-associated lipocalin (NGAL) is a predictor of AKI and Endothelial Progenitor Cells (EPCs) represent a potential repair mechanism for vascular lesions. We evaluated the diagnostic power of serum (s) and urine (u) NGAL in detecting a possible event of AKI in patients undergoing surgical treatment for AAA repair. We also investigated the influence of vascular injury on EPCs. Methods: We examined 50 patients who underwent open AAA repair. Blood and urine was collected preoperatively and every hour after surgery until 8 h to quantify sNGAL, uNGAL and circulating EPCs. AKI, was defined as a ≥25% decrease in eGFR compared with baseline values. Results: There was an inverse correlation between eGFR, sNGAL and uNGAL, while a direct correlation between sNGAL, APACHE II Score and EPCs was found. At receiver operating characteristic (ROC) analysis, sNGAL and uNGAL showed a very good diagnostic profile. Kaplan Meier curves showed that NGAL is a highly sensitive predictor of incidence of AKI. Univariate followed by multivariate Cox proportional hazard regression analysis showed that uNGAL and sNGAL predicted AKI independently of other potential confounders, including eGFR and APACHE II Score. Patients had at baseline and after surgical stress a significantly higher number of EPCs than control group. Methods: We examined 50 patients who underwent open AAA repair. Blood and urine was collected preoperatively and every hour after surgery until 8 h to quantify sNGAL, uNGAL and circulating EPCs. AKI, was defined as a ≥25% decrease in eGFR compared with baseline values. Results: There was an inverse correlation between eGFR, sNGAL and uNGAL, while a direct correlation between sNGAL APACHE II Score and EPCs was found. At receiver operating characteristic (ROC) analysis, sNGAL and uNGAL showed a very good diagnostic profile. Kaplan Meier curves showed that NGAL is a highly sensitive predictor of incidence of AKI. Univariate followed by multivariate Cox proportional hazard regression analysis showed that uNGAL and sNGAL predicted AKI independently of other potential confounders, including eGFR and APACHE II Score. Patients had at baseline and after surgical stress a significantly higher number of EPCs than control group. Conclusions: NGAL represents an independent renal predictor of incidence of AKI. EPCs reflect the degree of vascular damage and could be considered as an indicator of disease with a reparative-regenerative vascular-endothelial function.
    Current Vascular Pharmacology 06/2012; · 2.91 Impact Factor
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    ABSTRACT: To evaluate the balance between arginine-vasopressin (AVP) and apelin during hemodialysis and its role in hypotension onset and in the inflammation status. We enrolled 50 patients chronically treated with hemodialysis. We assessed plasmatic osmolality, AVP, apelin, mean blood pressure (BP), high-sensitivity C-reactive protein (hsCRP) and β(2)-microglobulin. Apelin rises during dialytic treatment (from 0.68 ± 0.34 to 1.89 ± 0.56 pg/ml, p < 0.0001), while plasmatic osmolality (from 325 ± 4.54 to 311 ± 1.20 mosm/kg H(2)O, p < 0.0001), AVP (from 4.28 ± 1.12 to 2.48 ± 0.50 pg/ml, p < 0.0001) and mean BP (from 124 ± 6 to 110 ± 7 mm Hg, p < 0.0001) decrease. At multivariate regression with respect to apelin, only mean BP remains (r = -0.95, p < 0.0001). We also correlated the AVP/apelin ratio with BP. Moreover, apelin is inversely related to hsCRP (r = -0.79, p < 0.0001). The AVP/apelin balance changes with plasmatic osmolality variations induced by hemodialytic sessions and could represent a physiopathological marker of arterial hypo- and hypertension. Finally, apelin appears inversely related to inflammation markers.
    Blood Purification 06/2012; 33(4):317-23. · 2.06 Impact Factor
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    ABSTRACT: Uremic patients are characterized by a "pro-arrhythmic substrate." Arrhythmia appearance during hemodialysis (HD) is an unexpected event with a high incidence of mortality and morbidity and difficult to record in patients repeatedly checked using electrocardiogram (ECG). Furthermore the carrying out of this important examination by classical devices during HD is uncomfortable and sometimes stressful for the patient. It may be very useful to monitor the patient's cardiac activity during the whole HD session. We tried to overcome these difficulties using Whealthy(®) (Wearable Health Care System), a wearable system in a T-shirt composed of conductors and piezoresistive materials, integrated to form fibers and threads connected to tissular sensors, electrodes, and connectors. ECG and pneumographic impedance signals are acquired by the electrodes in the tissue, and the data are registered by a small computer and transmitted via GPRS or Bluetooth.
    Renal Failure 04/2012; 34(6):818-20. · 0.94 Impact Factor
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    ABSTRACT: Obestatin is a 23-amino acid peptide hormone released from the stomach and is present not only in the gastrointestinal tract, but also in the spleen, mammary gland, breast milk and plasma. Obestatin appears to function as part of a complex gut-brain network whereby hormones and substances from the stomach and intestines signal the brain about satiety or hunger. In contrast to ghrelin, which causes hyperphagia and obesity, obestatin appears to act as an anorectic hormone, decreasing food intake and reducing body weight gain. Further studies have shown that obestatin is also involved in improving memory, regulating sleep, affecting cell proliferation, increasing the secretion of pancreatic juice enzymes and inhibiting glucose-induced insulin secretion. This hormone has not only been studied in the field of physiology but also in the fields of obesity and diabetes mellitus, and in patients with psychogenic eating disorders. Obestatin has a role in regulating the cell cycle by exerting proliferative effects that may be seen in cell physiology and oncology. Given the current controversy regarding the effects of obestatin and its cognate ligand, this article provides the latest review of the physiological and pathological characteristics of this hormone.
    Annals of Nutrition and Metabolism 12/2011; 59(2-4):193-9. · 1.66 Impact Factor
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    ABSTRACT: Tubulo-interstitial fibrosis constitutes the final common pathway for all pathological conditions that evolve towards chronic kidney disease, and transforming growth factor-β1 plays a key role in this process. Furthermore, neutrophil gelatinase-associated lipocalin appears not only to be a simple marker of renal injury but also an active player in disease progression. We are not yet able to control and modulate this phenomenon. Therefore, a better understanding of fibrogenic molecular mechanisms is necessary to detect possible therapeutic strategies that interfere with fibrosis and then stop the progression of renal disease. The line of research called 'regenerative medicine' works toward this. According to many authors, the formation of a fibrotic extracellular matrix disrupts the cells' polarity and stimulates their proliferation, creating conditions for cancer development. However, there is another plausible hypothesis: is it possible that fibrosis provides a sort of 'protection' from the development of a cancer as a consequence of the intense proliferation that characterizes any inflammatory process? In superior organisms, and also in humans, regeneration may have been selected negatively and replaced by fibrosis in the course of evolution, to warrant species survival: in fact, unchecked pluripotent cell production and proliferation can lead to tumour development and the potential death of a single individual. Hence, tumours might be the outcome of the failure of fibrotic processes, most likely due to some mediators predominating over others. So, valid experimental models are necessary to understand the interactions that exist between fibrosis and tumours and to evaluate the real advantage of therapies that aim to inhibit the fibrotic process at the renal level or that of other organs. The ideal approach would be to limit fibrosis and then organ function loss but without exposing the patient to risks of developing a tumour, starting from as early as the drugs prescribed.
    Nephrology Dialysis Transplantation 11/2011; 27(1):21-7. · 3.37 Impact Factor
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    ABSTRACT: NGAL (Neutrophil Gelatinase-Associated Lipocalin) is a small 25-kD peptide belonging to the lipocalin superfamily. Several studies highlight its role as an organ injury and disease activity biomarker. In the present review, instead, we wanted to study NGAL as a precocious marker of therapeutic response in renal and non-renal diseases (glomerulonephritis, vasculitis, LES, Crohn's disease and other chronic inflammatory pathologies). The obtained outcomes support the hypothesis that NGAL could be employed as a biomarker of response to different therapeutic schemes, because its levels sensibly and precociously change compared to other haematologic and biochemical parameters.
    Current pharmaceutical design 03/2011; 17(8):844-9. · 4.41 Impact Factor
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    ABSTRACT: Because of progressive population ageing and epidemic diffusion of type 2 diabetes mellitus in industrialized Countries, we are attending a growing incidence of end stage renal disease. This phenomenon has induced researchers to study potential alternative methods of renal function replacement. Actually, only dialytic methodics and renal transplant make possible survival of patients with terminal uremia, but both these therapeutic approaches show important limitations. The ideal solution would be represented by the possibility to "regenerate" the injured organ. This is the purpose of Regenerative Nephrology, a new medical domain which tries to develop new therapies through stimulation and induction in humans of regenerative processes already observed in other species, like reptiles and fishes. Such an ambitious and fascinating purpose requires a deep knowledge of the intricate networks which regulate the production of the hormones and mediators involved in the tissue regenerative processes. In this field the kidney embryonic development phases can represent a fundamental study model to acquire information about the reparative mechanisms of the structure and function of this excretory organ.
    European review for medical and pharmacological sciences 02/2011; 15(2):111-21. · 1.09 Impact Factor
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    ABSTRACT: End stage renal disease (ESRD) is associated with a high incidence of cardiovascular disease and cancer. Patients undergoing hemodialysis show a reduced number and an impaired function of endothelial progenitor cells (EPCs), which in physiological conditions contribute to repair the vascular damage. In patients with ESRD, massive oxidative genome damage has been demonstrated but the role of HD in causing it is still a controversial issue. The aim of our study was to analyze the effects of a single HD session on the number of cells marked with CD34 (including sub-type cells known to be EPCs); we then evaluated the genomic damage in these cells using COMET assay. We quantified CD34(+) cells in blood samples in 30 patients in hemodiafiltration treatment for 3.5 to 4 hours 3 times/week and in 30 healthy volunteers. In HD patients, blood samples were drawn at different time intervals: start of dialysis (T(0)), at the end of the treatment (T(end)) and 24 hours afterwards in the interdialytic day (T(inter)). Staining and analysis was performed using the ISHAGE (International Society of Hematotherapy and Graft Engineering) guidelines. EPCs count was conducted using a multiparameter flow cytometric lyse no-wash method. Genomic damage was evaluated by Comet assay. The number of CD34(+) cells in the HD patients at the beginning of the dialysis session (T(0)) was significantly lower than in healthy controls. HD patients showed a significant increase in CD34 number at the end of the session (T(end)) with respect to T(0). In the interdialytic period (T(int)), the number of CD34(+) cells was significantly reduced with respect to T(end). COMET assay performed on CD34(+) cells showed a higher basal level of genomic damage in HD patients than in controls; it increased in a statistically significant manner after the hemodialysis session, while in the interdialytic period it came back to T(0) level. Uremic status is characterized by lower levels of circulating EPCs, which increase after a single session of HD together with genomic damage to the CD34(+) cells.
    Journal of nephrology 03/2010; 23(3):328-34. · 2.02 Impact Factor
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    ABSTRACT: Erythropoietin synthesis is one of the essential adaptive responses to a hypoxic environment. In mammals, a renal oxygen sensor capable of stimulating erythropoietic hormone synthesis through a transcriptional factor called HIF (hypoxia-inducible factor) has long been identified. Recent research has demonstrated that cerebral astrocytes and skin keratocytes can also produce erythropoietin as a response to different oxygen concentrations. Therefore, it is possible to hypothesize a skin-brain-kidney link which, through erythropoietin production, modulates the oxygen contribution to tissues. Moreover, the results are not so unambiguous and further research on the pleiotropic effects of erythropoetin would be opportune.
    Giornale italiano di nefrologia: organo ufficiale della Societa italiana di nefrologia 01/2010; 27(6):609-15.
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    ABSTRACT: The aim of the present paper was to review recent developments in the management of patients with acute kidney injury or chronic kidney disease occurring secondary to either cancer itself or its therapy, with a focus on infiltration of the renal parenchyma, myeloma, tumor lysis syndrome, glomerular disease, thrombotic microangiopathy, chemotherapy-associated thrombotic microangiopathy, biphosphonate-induced renal diseases, acute kidney injury, and chronic kidney disease after hematopoietic cell transplantation. Further studies are awaited because a better knowledge of renal complications, which frequently occur in patients with oncohematologic diseases, would be conducive to making an early diagnosis and providing prompt therapy.
    Journal of Investigative Medicine 12/2009; 57(8):892-901. · 1.75 Impact Factor
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    ABSTRACT: In recent years the use of erythropoietin has exploded, and the anaemia of patients with chronic renal failure has been practically resolved with the administration of rHuEpo (recombinant human, Erythropoietin). However, as a result of an intense commercial campaign, strong therapies with this growth hormone, prescribed to achieve surprising sporting performances, got athletes to run the risk of thrombosis and vascular accidents because of red blood cells increase. Erythropoietin represents a significant subject of research. In fact, besides the ability of stimulating erythrocyte production, it has many pleiotropic effects. Several studies allow the assertion that EPO, in different concentrations, has protective effects mainly on central nervous system and cardiovascular system through various mechanisms, among which a key role seems to be held by the ability to stimulate angiogenesis. The consequent problem is that anaemia therapy with rHuEpo in patients with cancer may accelerate the progression of neoplastic disease by promoting tumour angiogenesis and, thus, metastasization. The study of angiogenic process in tumours led to the synthesis of drugs that, blocking VEGF, exert an anti-angiogenic action, contrasting cancer spread. However, benefits are relatively modest. Is erythropoietin perhaps the further angiogenic hormone to block in tumour pathology? Therefore, Epo plays a role in Regenerative Medicine since it intervenes in a persistent natural regenerative activity of humans: angiogenesis. The understanding of the regeneration mechanisms of complex structures in the adult salamander has opened original lines of research. Regenerative Medicine tries to develop therapeutic pathways through the stimulation of natural regenerative processes in humans.
    Current drug targets 10/2009; 10(10):1028-32. · 3.93 Impact Factor
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    ABSTRACT: In recent years the use of erythropoietin has exploded, and the anaemia of patients with chronic renal failure has been practically resolved with the administration of rHuEpo (recombinant human, Erythropoietin). However, as a result of an intense commercial campaign, strong therapies with this growth hormone, prescribed to achieve surprising sporting performances, got athletes to run the risk of thrombosis and vascular accidents because of red blood cells increase. Erythropoietin represents a significant subject of research. In fact, besides the ability of stimulating erythrocyte production, it has many pleiotropic effects. Several studies allow the assertion that EPO, in different concentrations, has protective effects mainly on central nervous system and cardiovascular system through various mechanisms, among which a key role seems to be held by the ability to stimulate angiogenesis. The consequent problem is that anaemia therapy with rHuEpo in patients with cancer may accelerate the progression of neoplastic disease by promoting tumour angiogenesis and, thus, metastasization. The study of angiogenic process in tumours led to the synthesis of drugs that, blocking VEGF, exert an anti-angiogenic action, contrasting cancer spread. However, benefits are relatively modest. Is erythropoietin perhaps the further angiogenic hormone to block in tumour pathology? Therefore, Epo plays a role in Regenerative Medicine since it intervenes in a persistent natural regenerative activity of humans: angiogenesis. The understanding of the regeneration mechanisms of complex structures in the adult salamander has opened original lines of research. Regenerative Medicine tries to develop therapeutic pathways through the stimulation of natural regenerative processes in humans.
    Current Drug Targets 09/2009; 10(10):1028-1032. · 3.85 Impact Factor
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    ABSTRACT: Erythropoietin (EPO), the main haematopoietic growth factor for the proliferation and differentiation of erythroid progenitor cells, is also known for its angiogenic and regenerative properties. In this study, we aimed to test the regenerative effects of EPO administration in an experimental model of Sea bass (Dicentrarchus labrax) subjected to amputation of the caudal fin. Erythropoietin-treated fishes (3000 UI of human recombinant EPO-alpha immediately after cutting and after 15 days) showed an increased growth rate of their fins compared with those untreated (anova variance: P: 0.01 vs. P: 0.04). By analysing fin length at established times (15 and 30 days after cut), EPO-treated fishes always showed an increased length compared with untreated ones (T-15: 1.1 +/- 0.2 vs. 0.7 +/- 0.2 cm, P: 0.03; T-30: 1.9 +/- 0.3 vs. 1.2 +/- 0.2 cm, P: 0.01). Moreover, exogenous EPO administration induced an enormous increase in EPO-blood levels at each observation time (T-15: 2240 +/- 210 vs. 16.7 +/- 1.8 mU mL(-1), P < 0.001; T-30: 2340 +/- 190 vs. 17.1 +/- 1.9 mU mL(-1), P < 0.001), whereas these levels remained quite unmodified in untreated fishes. Immunochemical analyses performed by confocal laser scanning microscopic observations showed an increased expression of EPO-receptors and PECAM-1 (an endothelial surface marker of vessels sprout) in the regenerating tissue, whereas no signs of inflammation or fibrosis were recognisable. All these findings confirm EPO as a new factor involved in regenerative processes, also suggesting a potential, future utility for new therapeutical applications in the field of human regenerative medicine.
    European Journal of Clinical Investigation 07/2009; 39(11):993-9. · 3.37 Impact Factor