PubMed Health⌕ Search

Biomedical subjects

Pietro Amedeo Modesti

Publications and source records attributed to Pietro Amedeo Modesti.

16 recordsLinked to original sources
PubMed2006

Role of endothelin-1 in exposure to high altitude: Acute Mountain Sickness and Endothelin-1 (ACME-1) study.

BACKGROUND: The degree of pulmonary hypertension in healthy subjects exposed to acute hypobaric hypoxia at high altitude was found to be related to increased plasma endothelin (ET)-1. The aim of the present study was to investigate the effects of ET-1 antagonism on pulmonary hypertension, renal water, and sodium balance under acute and prolonged exposure to high-altitude-associated hypoxia. METHODS AND RESULTS: In a double-blind fashion, healthy volunteers were randomly assigned to receive bosentan (62.5 mg for 1 day and 125 mg for the following 2 days; n=10) or placebo (n=10) at sea level and after rapid ascent to high altitude (4559 m). At sea level, bosentan did not induce any significant changes in hemodynamic or renal parameters. At altitude, bosentan induced a significant reduction of systolic pulmonary artery pressure (21+/-7 versus 31+/-7 mm Hg, P<0.03) and a mild increase in arterial oxygen saturation versus placebo after just 1 day of treatment. However, both urinary volume and free water clearance (H2OCl/glomerular filtration rate) were significantly reduced versus placebo after 2 days of ET-1 antagonism (1100+/-200 versus 1610+/-590 mL; -6.7+/-3.5 versus -1.8+/-4.8 mL/min, P<0.05 versus placebo for both). Sodium clearance and segmental tubular function were not significantly affected by bosentan administration. CONCLUSIONS: The present results indicate that the early beneficial effect of ET-1 antagonism on pulmonary blood pressure is followed by an impairment in volume adaptation. These findings must be considered for the prevention and treatment of acute mountain sickness.

Acute Disease↗
PubMed2006

Winter air-mass-based synoptic climatological approach and hospital admissions for myocardial infarction in Florence, Italy.

The aim of this study was to evaluate the relationship between the risk of hospital admission for myocardial infarction (MI) and the daily weather conditions during the winters of 1998-2003, according to an air-mass-based synoptic climatological approach. The effects of time lag and 2-day sequences with specific air mass types were also investigated. Studies concerning the relationship between atmospheric conditions and human health need to take into consideration simultaneous effects of many weather variables. At the moment few studies have surveyed these effects on hospitalizations for MI. Analyses were concentrated on winter, when the maximum peak of hospitalization occurred. An objective daily air mass classification by means of statistical analyses based on ground meteorological data was carried out. A comparison between air mass classification and hospital admissions was made by the calculation of a MI admission index, and to detect significant relationships the Mann-Whitney U test, the analysis of variance, and the Bonferroni test were used. Significant increases in hospital admissions for MI were evident 24h after a day characterized by an anticyclonic continental air mass and 6 days after a day characterized by a cyclonic air mass. Increased risk of hospitalization was found even when specific 2-day air mass sequences occurred. These results represent an important step in identifying reliable linkages between weather and health.

Aged↗
PubMed2006

Perioperative myocardial infarction in non-cardiac surgery. Pathophysiology and clinical implications.

Advances in surgical and anaesthetic techniques and an aging patient population have resulted in more complex procedures being performed in greater numbers of aged subjects and in patients with a high likelihood of significant cardiovascular disease. Nearly one fourth of non-cardiac surgical procedures (major intra-abdominal, thoracic, vascular, and orthopaedic procedures) performed in persons older than 65 years have been found to be associated with significant perioperative cardiovascular morbidity and mortality. During previous years the main attempt was to define strategies to accurately estimate perioperative cardiovascular risk based either on the characteristics of surgery and on patient characteristics. More recently preventive medical strategies have been proposed. Therefore, the physician has to be aware of the key elements useful to calculate the perioperative cardiovascular risk, and of the medical preventive treatment or further interventions to adopt in patients candidate to surgery.

Humans↗
PubMed2006

Relationship between work-related accidents and hot weather conditions in Tuscany (central Italy).

Nowadays, no studies have been published on the relationship between meteorological conditions and work-related mortality and morbidity in Italy. The aim of this study was to evaluate the relationship between hot weather conditions and hospital admissions due to work-related accidents in Tuscany (central Italy) over the period 1998-2003. Apparent temperature (AT) values were calculated to evaluate human weather discomfort due to hot conditions and then tested for work accident differences using non-parametric procedures. Present findings showed that hot weather conditions might represent a risk factor for work-related accidents in Italy during summer. In particular early warming days during June, characterized by heat discomfort, are less tolerated by workers than warming days of the following summer months. The peak of work-related accidents occurred on days characterized by high, but not extreme, thermal conditions. Workers maybe change their behaviour when heat stress increases, reducing risks by adopting preventive measures. Results suggested that days with an average daytime AT value ranged between 24.8 degrees C and 27.5 degrees C were at the highest risk of work-related accidents. In conclusion, present findings might represent the first step for the development of a watch/warning system for workers that might be used by employers for planning work activities.

Accidents, Occupational↗
PubMed2005

Weather-related changes in 24-hour blood pressure profile: effects of age and implications for hypertension management.

A downward titration of antihypertensive drug regimens in summertime is often performed on the basis of seasonal variations of clinic blood pressure (BP). However, little is known about the actual interaction between outdoor air temperature and the effects of antihypertensive treatment on ambulatory BP. The combined effects of aging, treatment, and daily mean temperature on clinic and ambulatory BP were investigated in 6404 subjects referred to our units between October 1999 and December 2003. Office and mean 24-hour systolic BP, as well as morning pressure surge, were significantly lower in hot (>90th percentiles of air temperature; 136+/-19, 130+/-14, and 33.3+/-16.1 mm Hg; P<0.05 for all), and higher in cold (<10th percentiles) days (141+/-12, 133+/-11, and 37.3+/-9.5 mm Hg; at least P<0.05 for all) when compared with intermediate days (138+/-18, 132+/-14, and 35.3+/-15.4 mm Hg). At regression analysis, 24-hour and daytime systolic pressure were inversely related to temperature (P<0.01 for all). Conversely, nighttime systolic pressure was positively related to temperature (P<0.02), with hot days being associated with higher nighttime pressure. Air temperature was identified as an independent predictor of nighttime systolic pressure increase in the group of elderly treated hypertensive subjects only. No significant relationship was found between air temperature and heart rate. Our results show for the first time that hot weather is associated with an increase in systolic pressure at night in treated elderly hypertensive subjects. This may be because of a nocturnal BP escape from the effects of a lighter summertime drug regimen and may have important implications for seasonal modulation of antihypertensive treatment.

Aged↗
PubMed2005

Relationships between weather and myocardial infarction: a biometeorological approach.

OBJECTIVES: To calculate threshold values of weather discomfort which increase the risk of hospital admissions for myocardial infarction in winter and summer. BACKGROUND: Notwithstanding heat waves were reported to acutely increase hospital admissions for cardiovascular diseases, large surveys failed to reveal any increase of event rates with increasing air temperature. However, the assessment of air temperature does not allow evaluation of the actual discomfort perception caused by the combination of different meteorological parameters. METHODS: Hospital admissions for myocardial infarction for the period 1998-2002 in Florence, Italy, were considered. The percentages of variation of daily event rates according to daily mean air temperature variations were preliminary derived by using a regression analysis. An alternative biometeorological approach, considering the Apparent Temperature Index (ATI) in summer, and the New U.S./Canada Wind Chill Temperature Index (NWCTI) in winter, which combine air temperature, relative humidity and wind velocity, was then used. RESULTS: The traditional approach showed that daily event rates significantly increased with daily mean air temperature decrease (10 degrees C decrease were associated with 19% increase in daily event rates for people older than 65 years), but failed to show any negative effect caused by hot climatic conditions. Conversely the biometeorological approach allowed to show that at least 9 h per day of severe discomfort caused by hot conditions significantly increased the rate of admission (P<0.01). CONCLUSIONS: This approach might be useful for the development of an operative weather watch/warning system for population and for hospital professional care.

Aged↗
PubMed2004

Cardiac angiotensin II participates in coronary microvessel inflammation of unstable angina and strengthens the immunomediated component.

Angiotensin (Ang) II is now recognized to be a mediator of a wide variety of inflammatory processes. This study investigated renin-angiotensin system (RAS) components and a number of inflammatory mediators in left ventricular biopsies from 2-vessel disease unstable angina (UA) (n=43) and stable angina (SA) (n=15) patients undergoing coronary bypass surgery. Biopsy samples from 6 patients undergoing valve replacement for mitral stenosis served as controls. UA patients were randomly assigned to angiotensin-converting enzyme (ACE)-inhibitor (ramipril), AT1 antagonist (valsartan), or placebo and treated during the 5 days preceding coronary bypass surgery, performed from 6 to 9 days after coronary angiography. During coronary angiography coronary blood flow was measured and samples were obtained from aorta and coronary sinus for determination of Ang I and Ang II gradients. The hearts of UA patients produced Ang II in a greater amount than in SA patients (P<0.01). UA biopsy samples showed numerous DR+ cells, identified as lymphocytes, macrophages, and endothelial cells. Reverse-transcriptase polymerase chain reaction showed overexpression of AGTN, ACE, and AT1-R genes, as well as upregulation of TNF-alpha, IL-6, IFN-gamma, and iNOS genes (P<0.01), with no differences between nonischemic and potentially ischemic areas. AGTN, ACE, and cytokine genes were mainly localized on endothelial cells. Ramipril and valsartan markedly decreased the expression levels of TNF-alpha, IL-6, and iNOS, and, to a lesser extent, of IFN-gamma genes, but did not affect the number of DR+ cells, with no significant difference between the 2 treatments. These results show that locally generated Ang II amplifies the immunomediated inflammatory process of coronary microvessels occurring in unstable angina.

Adult↗
PubMed2003

Different growth factor activation in the right and left ventricles in experimental volume overload.

Mechanical factors play a key role in activation of cardiac growth factor response in hemodynamic overload, and both cooperate in myocardial remodeling. The present study was performed to investigate whether a different growth factor response is activated in the right and left ventricles in aortocaval fistula and its effects on regional myocardial adaptation. Relations between regional growth factor expression (angiotensin II, insulin-like growth factor-I, and endothelin-1), myocyte shape changes, and collagen deposition were investigated at mRNA and peptide levels in adult pigs after the creation of an aortocaval fistula distal to the renal arteries (n=15) and in sham-operated animals (n=15). The role of angiotensin II was investigated by the administration of angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist. In the left ventricle, pure volume overload was accompanied by persistent increase of insulin-like growth factor-I mRNA expression, peptide concentration (2.2-fold versus sham at 3 months, P<0.05), and significant increase of myocyte length (+29% at 3 months, P<0.05). Conversely, the mixed pressure-volume overload faced by the right ventricle resulted in significant regional overexpression of all growth factors investigated (angiotensin II, insulin-like growth factor-I, and endothelin-1), with corresponding increase of myocyte diameter and length and collagen deposition (+117% at 3 months). Collagen accumulation in the right ventricle as well as the increase in right ventricular end-diastolic pressure at the 3-month observation were inhibited by angiotensin II antagonism. The left and right ventricles respond differently to aortocaval fistula, and local growth factor expression is closely related to the regional myocardial adaptation.

Adaptation, Physiological↗
PubMed2003

Immunomediated and ischemia-independent inflammation of coronary microvessels in unstable angina.

This study investigated whether the myocardium is involved in the acute inflammatory reaction associated with bursts of unstable angina (UA). We looked for the presence of activated DR+ inflammatory cells and the expression patterns, localization, and immunostaining identification of genes for cytokines (IL-1beta, TNF-alpha, IL-6, and IFN-gamma), MCP-1, and iNOS in the left ventricle biopsies from 2-vessel disease anginal patients, 24 with UA and 12 with stable angina (SA), who underwent coronary bypass surgery. Biopsy specimens from 6 patients with mitral stenosis who underwent valve replacement were examined as control hearts (CHs). Plasma levels of IL-2 soluble receptor (sIL-2R) were measured as a marker of systemic immune reaction. In CHs, DR+ cells were undetectable, and cytokine and iNOS mRNA expression were negligible. UA patients had higher sIL-2R levels than SA patients (P<0.01), and their biopsy specimens showed both numerous DR+ cells identified as lymphocytes, macrophages, endothelial cells, and elevated expression levels of cytokine and iNOS genes (from 2.4- to 6.1-fold vs SA; P<0.01). Cytokine and iNOS genes and proteins were localized in endothelial cells without involvement of myocytes. IL-1beta and MCP-1 mRNAs were nearly undetectable. No significant differences were found in the number of DR+ cells, levels of cytokine, and iNOS genes between potentially ischemic and nonischemic left ventricle areas. In SA specimens, DR+ cells were very rare and only mRNAs for TNF-alpha and iNOS genes were overexpressed versus CHs. These results indicated that an acute immunomediated inflammatory reaction, essentially involving coronary microvessels, is demonstrable in UA patients.

Adult↗
PubMed2003

[Angiotensin-converting enzyme inhibitors :from vasoactive drugs to cardiovascular prevention tools].

Abundant evidence showed that angiotensin-converting enzyme (ACE)-inhibitors reduce long-term cardiovascular morbidity and mortality rates in patients with heart failure and myocardial infarction. More recent studies revealed clinical benefits also in hypertensive patients with comorbidity and lead to an extension of clinical indications. Indeed in patients with severe hypertension differences between drugs are hardly detectable because the risk reduction is mainly related to the control of blood pressure values independent of the type of therapy. Conversely in the presence of comorbid conditions, especially in diabetics, the association of ACE-inhibitors with antihypertensive treatments proved its efficacy in reducing cardiovascular morbidity and mortality so that the role of mechanisms extending beyond blood pressure reduction can be postulated.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Release of preformed Ang II from myocytes mediates angiotensinogen and ET-1 gene overexpression in vivo via AT1 receptor.

UNLABELLED: The role of angiotensin II in pressure overload is still debated because notwithstanding its effects on myocyte contractility angiotensin II is not an obligatory factor for the development of hypertrophy. To define the role of angiotensin II in acute pressure overload we studied the effects of AT1 blockade (valsartan 80mg per day) on myocardial contractility, cardiac growth factor gene expression, and myocardial hypertrophy in aortic banded (60mmHg) pigs. Acute pressure overload caused an abrupt reduction of myocardial contractility, measured by the end-systolic stiffness constant, and a sharp increase in end-systolic stress which rapidly normalized (within 12h) in the placebo group. In AT1-blocked animals end-systolic stiffness constant remained significantly depressed up to 24h and end-systolic stress was still elevated up to 48h (both P<0.05 vs placebo). In both groups confocal microscopy revealed that granular staining of angiotensin II in cardiomyocyte cytoplasm disappeared after 30min of pressure overload. AT1 blockade abolished following cardiac overexpression of angiotensinogen and endothelin-1 genes as shown in RT-PCR studies and the consequent angiotensin II and endothelin-1 release in the coronary circulation. Conversely, insulin-like growth factor-I and ACE mRNA overexpression, as well as the onset of left ventricular mass increase, were not significantly affected by AT1 blockade. IN CONCLUSION: (1) mechanical stress releases preformed angiotensin II from myocyte in vivo; (2) the AT1 blockade abolishes cardiac angiotensin II and endothelin-1 production with delayed recovery of myocardial contractility; whereas (3) the overexpression of insulin-like growth factor-I gene and the development of myocardial hypertrophy are not angiotensin II-mediated effects.

Angiotensin II↗
PubMed2002

ET(B) receptor in renal medulla is enhanced by local sodium during low salt intake.

Renal endothelin-1 participates in sodium and water handling, and its urinary excretion is increased in sodium-retentive states. We compared the cortical and medullary renal expression of prepro-endothelin-1, endothelin-converting enzyme-1, and endothelin type A and type B receptors in patients who underwent nephrectomy after normal (108 mmol/d NaCl; n=6) or low (20 mmol/d NaCl; n=6) sodium diet and investigated whether sodium exerts a direct role on endothelin receptor binding in vitro. With normal sodium diet prepro-endothelin-1 mRNA was 3-fold higher in renal medulla than in cortex (P<0.01), whereas endothelin-converting enzyme-1 mRNA was equally distributed. Endothelin-1 receptor density was 2-fold higher in renal medulla than in cortex (P<0.05). Type B was the main receptor subtype in both regions. In the renal cortex, low sodium diet caused a 194% increase in prepro-endothelin-1 mRNA (P<0.05), whereas endothelin-converting enzyme-1 type B and type A receptors remained unchanged. In contrast, in the renal medulla the increase in prepro-endothelin-1 mRNA (+30%, P<0.05) was associated with a selective increase in type B receptor for both mRNA expression (+37%, P<0.05) and binding density (+55%, P<0.05). Increasing in vitro sodium concentrations between 154 and 308 mmol/L significantly enhanced type B receptor density (P<0.05) and affinity (P<0.05). In conclusion, during low sodium diet, renal prepro-endothelin-1 synthesis increases mainly in the renal cortex (where no changes in receptors occur), whereas type B receptor is selectively enhanced in the renal medulla. The range of sodium concentrations that are physiologically present in vivo in the renal medulla selectively modulate type B receptor density and affinity.

Aspartic Acid Endopeptidases↗
PubMedDate not supplied

[Drug-induced nephropathy].

Drug-induced nephropathy is an important cause of renal injury which is reversible when detected early. Unfortunately, the clinical signs may not be apparent in the early phases and the nephropathy may become evident only at an advanced stage with an acute deterioration of the renal functions or chronic renal insufficiency. It is particularly important not only to know the nephrotoxic potential of the different drug groups, but especially to recognize the patient's risk factors that could be modified or that should preclude the use of these drugs. The presence of comorbid conditions such as older age, diabetes mellitus and congestive heart failure significantly influences the patient's ability to recover from the toxic effects. Many drugs can injure the kidneys, but they cause renal injury via only a few common mechanisms. The aim of the present review is to examine the main clinical presentations of drug-induced nephropathy.

Acute Kidney Injury↗