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Biomedical subjects

Lorenzo A Calò

Publications and source records attributed to Lorenzo A Calò.

At least 19 recordsLinked to original sources
PubMed2007

Phosphate salivary secretion in hemodialysis patients: implications for the treatment of hyperphosphatemia.

BACKGROUND/AIMS: Hyperphosphatemia is recognized as contributing to the increased risk of cardiac death in end-stage renal disease (ESRD) and hemodialysis (HD) patients. Currently available pharmacologic treatment for hyperphosphatemia is based on phosphate binders but, despite treatment, only half of the patients fall within the range for serum phosphorus of the K/DOQI guidelines. Therefore, there is a need to identify other therapeutic approaches in order to reduce serum phosphate. Salivary fluid contains phosphate which, if related to the daily salivary secretion (1,000-1,880 ml), may raise interest in order to identify further additive approaches to phosphorus removal in uremic patients, while data about salivary phosphate secretion in ESRD patients are controversial. METHODS: This study evaluates salivary phosphate secretion in 68 HD patients compared with 30 healthy subjects. Saxon's test confirmed normal salivary function in patients and controls. Salivary calcium and serum phosphate, calcium and PTH were also measured. RESULTS: HD patients had significantly higher salivary phosphorus levels compared with healthy controls: 30.35 (26.5-34.6) vs. 12.1 (10.58-14.73) mg/dl (p < 0.0001), and this significantly correlated (p < 0.0001) with serum phosphorus. Multiple regression analysis confirmed serum phosphorus as the only predictor (p < 0.0001) of salivary phosphorus. CONCLUSIONS: Given the functional secretive similarity between salivary glands and the kidneys, this increased salivary phosphate secretion might be interpreted as being compensatory in the presence of renal failure. Absorption of the increased salivary phosphate secretion, however, may worsen hyperphosphatemia; therefore, the binding of salivary phosphate might be considered as a further therapeutic approach to hyperphosphatemia in ESRD.

Female↗
PubMed2007

RhoA/Rho-kinase pathway: much more than just a modulation of vascular tone. Evidence from studies in humans.

RhoA/Rho-kinase signaling and its relationship/balance with the nitric oxide level, angiotensin II and vasopressors for cardiovascular pathophysiology is of increasing importance, and its involvement goes far beyond blood pressure regulation. The deep involvement of this pathway in cardiovascular biology is now known to include a wide spectrum of conditions relating to the long-term complications of hypertension, and in general of cardiovascular pathophysiology, such as changes in cardiovascular structure (remodeling) and the induction of atherosclerosis, involvement in the pathophysiological relationships between inflammation and hypertension, and in those between hypertension, glucose metabolism and insulin resistance. Studies from our laboratory have made an important contribution to the understanding of the cellular and molecular mechanisms mediated by the RhoA/Rho-kinase pathway, which include all the aspects of cardiovascular pathophysiology in which this pathway plays a role. In addition, if it is considered that our contribution to the clarification of these mechanisms only comes from studies in humans, their impact on the scenario of the RhoA/Rho-kinase pathway's biology, essentially supported by studies 'in vitro' or in animal models, is immediate. This review examines all the aspects of RhoA/Rho-kinase signaling in the light of the available data, and gives an updated and useful overall picture of its involvement in cardiovascular pathophysiology.

Cardiovascular Diseases↗
PubMed2006

Early markers of inflammation in a high angiotensin II state--results of studies in Bartter's/Gitelman's syndromes.

BACKGROUND: Inflammation has been increasingly recognized as playing a critical role in hypertension and atherosclerosis as reflected by overexpression and increased production of a variety of pro-inflammatory mediators. As angiotensin II (Ang II) also plays a major role in these diseases, the relationship between inflammation and Ang II has drawn increasing scrutiny. This study explores Ang II effects in Bartter's and Gitelman's syndromes (BS/GS) which do not develop hypertension and related cardiovascular remodelling and atherosclerosis, in spite of high Ang II levels and activation of the renin-angiotensin-aldosterone system while the NO system is up-regulated. METHODS: We evaluated the plasma levels of inflammation-associated markers, C-reactive protein (CRP), serum amyloid A (SAA), vascular cell adhesion molecules (VCAM) and intercellular adhesion molecules (ICAM), and the inflammation-related cytokines interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) using immunonephelometric and ELISA-based assays. RESULTS: The study demonstrated that all markers of inflammation except TNF-alpha, were unchanged in BS/GS (2.51+/-0.62 mg/l in BS/GS vs 1.7+/-0.6 in controls for CRP; 4.56+/-1.09 mg/l in BS/GS vs 4.51+/-1.0 for SAA; 1.84+/-0.27 ng/l in BS/GS vs 2.1+/-0.3 for IL-6; 449+/-83 ng/ml in BS/GS vs 410+/-92 for VCAM and 234+/-26 ng/ml in BS/GS vs 185+/-22 for ICAM), while TNF-alpha was increased (10.5+/-2.03 vs 3.68+/-0.2, P = 0.0001). CONCLUSIONS: The results of this study stress the critical role played by Ang II in controlling vascular biology including inflammation-related processes as well as highlighting the utility of BS/GS in investigating these pathways.

Acute-Phase Proteins↗
PubMed2006

A role for heme oxygenase-1 in the antioxidant and antiapoptotic effects of erythropoietin: the start of a good news/bad news story?

Erythropoietin (EPO) is the major regulator of erythropoiesis. EPO's actions have been shown to be antiapoptotic and dependent on JAK2 signaling and Akt phosphorylation. These effects serve as link between EPO and heme oxygenase-1 (HO-1). HO-1 is an inducible enzyme with potent antioxidant and antiapoptotic activities which are regulated by Akt signaling. EPO's ability to alter cellular systems that involve apoptosis and oxidants suggests that EPO treatments are likely to have multiple and different effects which may start a good news/bad news story. Recombinant human EPO is the recognized treatment of choice to address anemia and to stimulate erythropoiesis in chronic renal failure patients, through its antiapoptotic action which likely involves HO-1. On the other hand, EPO treatment to address anemia in cancer patients, while providing significant improvements in cancer patients' quality of life, its effects on survival are equivocal, likely due to its linkage with HO-1. Two clinical trials of EPO in patients with solid tumors have, in fact, shown specific negative effects on survival. However, EPO's effect on tumor growth and survival is not uniformily pro growth and pro survival, as EPO may act synergistically with chemotherapy to induce apoptosis. Finally, compounds have been synthesized that do not trigger EPO receptor and thus may allow experimental distinction and, therefore, at least potentially affect at the clinical level the tissue-protective effects of EPO (e.g., antiapoptosis) without provoking its other potentially detrimental effects.

Animals↗
PubMed2006

Antioxidant effect of L-carnitine and its short chain esters: relevance for the protection from oxidative stress related cardiovascular damage.

BACKGROUND: Increased oxidative stress is associated with all cardiovascular risk factors and reactive oxygen species appear to be the principal mediators of cardiomyocite dysfunction in various cardiovascular diseases. Carnitine has been shown to be effective in pathologic conditions characterized by increased oxidative stress and an antioxidant effect of L-carnitine and its derivatives has been described but the specific mechanism is unclear. METHODS: We evaluated in human endothelial cells in culture the effect of L-carnitine (C), acetyl-L-carnitine (AC) and propionyl-L-carnitine (PC) on gene and protein expression (RT-PCR and Western blot) of oxidative stress related proteins heme oxygenase-1 (HO-1) and of endothelial NO synthase (ecNOS) in absence and presence of oxidative stress induced by H2O2. RESULTS: HO-1 as well as ecNOS gene and protein expression significantly increased upon Carnitines incubation. Induction of oxidative stress increased HO-1 gene expression compared to basal condition (0.62+/-0.02 densitometric units vs. 0.48+/-0.05, p<0.01) while decreased ecNOS gene expression (0.75+/-0.04 vs. 0.40+/-0.08, p<0.001). These results were paralleled by similar results at protein level. Coincubation of C (0.5-1.0-2.0 mM), AC (0.1-0.2-0.4 mM) and PC (0.05-0.1-0.2 mM) with H2O2 further increased HO-1 gene expression and not only normalized vs. H2O2 but even increased vs. basal ecNOS mRNA. HO-1 and ecNOS gene expression was also paralleled at protein level by coincubation with C, AC and PC of cells exposed to oxidative stress. CONCLUSION: This is the first report that has utilized a molecular biological approach to demonstrate a direct stimulatory effect of Carnitines on gene and protein expression of the oxidative stress related markers HO-1 and ecNOS. As HO-1 and NO are known as antioxidant, antiproliferative and anti-inflammatory, their increased expression would be expected to protect from oxidative stress related cardiovascular risk factors and myocardial damage, therefore adding this effect to the multiple pathways involved in the effects of carnitines.

Apoptosis↗
PubMed2006

Aldosterone and refractory hypertension: a prospective cohort study.

BACKGROUND: Resistant hypertension is common in clinical practice. The aim of our study was to evaluate inappropriate aldosterone activity in causing resistance to antihypertensive therapy. METHODS: Among the patients consecutively evaluated for the first time between 1995 and 2001, we selected all those (n = 157) with an aldosterone-to-renin ratio (ARR) >or=25 (ng/dL)/(ng/mL/h), and plasma aldosterone >or=12 ng/dL. Eight patients with Conn adenoma were excluded from the study. Fifty-eight were diagnosed as idiopathic aldosteronism (IHA), the other 91 patients, who did not meet the criteria for primary aldosteronism, were operatively classified as aldosterone-associated hypertension (AAH). As a control group, we randomly chose 160 patients with essential hypertension and plasma aldosterone <12 ng/dL (EH). Antihypertensive treatment was given in accordance to World Health Organization Guidelines (1999). The study end point was blood pressure (BP) <140/90 mm Hg. RESULTS: During follow-up (22 +/- 2 months), 24 (41.4%) patients with IHA, 35 (38.5%) with AAH, and 72 (54.0%) with EH reached the end point. According to survival analysis, AAH and IHA patients reached the end point in a smaller fraction and in a longer time compared with EH patients, with no difference between IHA and AAH. At the end of follow-up, IHA and AAH patients had higher diastolic BP than EH patients with no difference between IHA and AAH. CONCLUSIONS: Patients with elevated aldosterone plasma levels develop resistant hypertension, even in the absence of clinically diagnosed primary aldosteronism. Their identification will allow a targeted therapy and a more effective BP reduction.

Aldosterone↗
PubMed2006

Oxidative stress and post-transplant hypertension in pediatric kidney-transplanted patients.

OBJECTIVE: To test the hypothesis that oxidative stress signaling contributes to post-transplant endothelial dysfunction and hypertension in pediatric post-transplant hypertension. STUDY DESIGN: This study evaluated in 16 pediatric renal transplant patients, divided in two groups based on the presence of post-transplant hypertension, the oxidative stress status measuring the gene expression (reverse transcription-polymerase chain reaction) of two major oxidative stress-related proteins, p22(phox) and heme oxygenase-1 (HO-1). Total plasma antioxidant power (ELISA) was also evaluated. RESULTS: Mononuclear cell p22(phox) gene expression was higher in hypertensive patients compared with the normotensive group (0.91 +/- 0.06 vs 0.79 +/- 0.08 densitometric units, P < .02), whereas HO-1 RNA production and total plasma antioxidant power were higher in the normotensive group (0.38 +/- 0.04 vs 0.20 +/- 0.11 d.u., P < .006, and 1189.35 +/- 145.75 vs 772.71 +/- 196.03 micromol/L, P < .01, respectively). CONCLUSIONS: Oxidative stress is associated with post-transplant hypertension in hypertensive pediatric kidney-transplant patients, who therefore are at risk of oxidative stress-induced organ damage. They might benefit from treatments addressing not only hypertension but also oxidant-related complications.

Adolescent↗
PubMed2006

Reduced expression of regulator of G-protein signaling 2 (RGS2) in hypertensive patients increases calcium mobilization and ERK1/2 phosphorylation induced by angiotensin II.

CONTEXT: RGS2 (regulators of G-protein signaling) is a negative regulator of Galphaq protein signaling, which mediates the action of several vasoconstrictors. RGS2-deficient mouse line exhibits a hypertensive phenotype and a prolonged response to vasoconstrictors. OBJECTIVE: To compare RGS2 expression in peripheral blood mononuclear cells (PBMs) and cultured fibroblasts from normotensive subjects and hypertensive patients. METHODS: PBMs were isolated from 100 controls and 150 essential hypertensives. Additionally, fibroblasts were isolated from skin biopsy of 11 normotensives and 12 hypertensives and cultured up to the third passage. Quantitative mRNA and protein RGS2 expression were performed by real-time quantitative reverse transcriptase-polymerase chain reaction and by immunoblotting, respectively. Free Ca measurement was performed in monolayers of 24-h serum-deprived cells, using FURA-2 AM. Phosphorylation of the extracellular signal-regulated kinases ERK1/2 was measured by immunoblotting. Polymorphism (C1114G) in the 3' untranslated region of the RGS2 gene was investigated by direct sequencing and real-time polymerase chain reaction (PCR). RESULTS: RGS2 mRNA expression was significantly lower in PBM and in fibroblasts from hypertensives, in comparison to normotensives. C1114G polymorphism was associated with RGS2 expression, with the lowest values in GG hypertensives. The 1114G allele frequency was increased in hypertensives compared with normotensives. Angiotensin II-stimulated intracellular Ca increase and ERK1/2 phosphorylation were higher in fibroblasts from hypertensive patients compared with control subjects, and in those with the G allele, independently of the blood pressure status. The angiotensin II-stimulated Ca mobilization and ERK1/2 phosphorylation were negatively correlated with RGS2 mRNA expression. CONCLUSION: Low expression of RGS2 contributes to increased G-protein-coupled signaling in hypertensive patients. The allele G is associated with low RGS2 expression and blood pressure increase in humans.

Adult↗
PubMed2006

Blood pressure in acute ischemic stroke and mortality: a study with noninvasive blood pressure monitoring.

BACKGROUND: In acute ischemic stroke, a transient elevation of blood pressure is common; its significance and its relationship with the neurological outcome are still unclear. METHODS: In 71 consecutive patients with acute ischemic stroke, aged 25-94 years, admitted to our unit, we investigated the relationships between the blood pressure variation during the first 24 h and mortality at 3 months (study endpoint). Neurological status was assessed with the National Institutes of Health Stroke Scale. Blood pressure was measured with bedside noninvasive blood pressure monitoring every 15 min. The mean of four measurements at the emergency department and the mean of 12 measures (during a 3-h interval) at 12 and at 24 h after stroke onset were considered for analysis. Antihypertensive treatment was given in accordance with the Recommendations for Stroke Management of European Stroke Initiative. RESULTS: In the whole series, 21% were atherothrombotic, 32% cardioembolic, 34% lacunar, and 13% of unknown or other cause. Blood pressure was 160+ or -3/86+ or -2 mmHg at the emergency department, 148+ or -3/82+ or -2 mmHg at 12 h, and 147+ or -3/81+ or -2 mmHg at 24 h (P<0.05). Four patients (11%) of those in whom mean blood pressure decreased >5 mmHg, and 12 (33%) of the others, in whom mean blood pressure decreased < or =5 mmHg or did not decrease, reached the endpoint (P<0.05). According to the multivariate Cox model, NIHSS score at the emergency department (95% confidence interval: 1.025-1.238, P=0.013) and age (95% confidence interval: 1.007-1.259, P=0.038) were predictors of reaching the endpoint, whereas mean blood pressure reduction 24 h after stroke onset had a protective effect (95% confidence interval: 0.845-0.995, P=0.038). Diabetes, mean blood pressure at the emergency department and the need for antihypertensive therapy did not correlate with the outcome. CONCLUSIONS: Noninvasive blood pressure monitoring during the first 24 h of acute ischemic stroke may be useful in the prognostic stratification by showing moderate blood pressure decrease, either spontaneous or drug induced, which is associated with a favorable prognosis at 3 months.

Adult↗
PubMed2006

Effect of doxazosin on oxidative stress-related proteins in benign prostatic hyperplasia.

BACKGROUND AND OBJECTIVES: Oxidative stress can induce cell mutations or proliferation which then can progress to carcinogenesis or remodeling. The same oxidative stress-mediated mechanism could participate in prostate cell proliferation and remodeling present in benign prostatic hyperplasia (BPH). Doxazosin induces prostate epithelial and stromal cell apoptosis through production of transforming growth factor-beta (TGF-beta), but cellular mechanisms are not completely clarified. In 10 prostate samples from BPH untreated patients who underwent TUR, we have assessed the gene and protein expression of: p22(phox) (subunit of NAD(P)H oxidase essential for O(2)(-) production); heme oxygenase-1 (HO-1) (induced by oxidative stress and antiapoptotic); TGF-beta (inhibitor of prostatic epithelial and stromal cell growth); the in vitro effect of doxazosin on expression of these markers. METHODS: RT-PCR and Western blot with specific primers and antibodies. p22(phox), HO-1 and TGF-beta were quantified by the ratio between their PCR and Western blot products and GAPDH. RESULTS: Doxazosin significantly reduced p22(phox) gene and protein expression (0.61 +/- 0.04 vs. 0.36 +/- 0.04 d.u., p < 0.0002; 0.85 +/- 0.03 vs. 0.47 +/- 0.03, p < 0.0001, respectively). Doxazosin concentration dependently reduced HO-1 gene and protein expression (0.57 +/- 0.07 vs. 0.49 +/- 0.06 d.u. (1 microM) p < 0.04, vs. 0.22 +/- 0.08 (10 microM) p < 0.0001; 0.78 +/- 0.04 vs. 0.44 +/- 0.1 (10 microM) p < 0.003 respectively) and increased TGF-beta protein expression (0.58 +/- 0.05 vs. 0.74 +/- 0.16 (1 microM) n.s. vs. 0.81 +/- 0.07 (10 microM) p < 0.01). CONCLUSIONS: Induction of oxidative stress-related proteins seems to be involved in the prostate cell proliferation and remodeling present in BPH. Doxazosin may reduce oxidative stress through reduction of p22(phox). Surprisingly, HO-1, which is induced and protected by oxidative stress, is also reduced by doxazosin. HO-1 is a potent antiapoptotic factor and downregulator of TGF-beta. From the results of this preliminary study it could be proposed that the proapoptotic effect of doxazosin could be mediated, at least in part, through the contemporary inhibition of HO-1.

Aged↗